The Genus Tamarix Traditional Uses, Phytochemistry, and Pharmacology

Journal of Ethnopharmacology 246 (2020) 112245

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Journal of Ethnopharmacology

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Review The genus Tamarix: Traditional uses, phytochemistry, and pharmacology T Roodabeh Bahramsoltania,b, Mahdieh Kalkhoranic, Syed Mohd Abbas Zaidid, ∗ Mohammad Hosein Farzaeie,f, Rahimi Rojaa,b, a Department of Traditional Pharmacy, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran b PhytoPharmacology Interest Group (PPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran c Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran d Department of Moalajat (Internal Medicine), Hakim Syed Ziaul Hasan Government Unani Medical College, Bhopal, India e Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran f Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

ARTICLE INFO ABSTRACT

Keywords: Ethnopharmacological relevance: The genus Tamarix L., with the common name of tamarisk, consists of more than Tamarisk 60 species of halophyte plants which are used for medicinal purposes such as infections, wounds, and liver and Tamarix spleen disorders by local people mostly in Asian and African countries. Traditional medicine Aim of the review: In spite of the potential health benefits of Tamarix spp., the plant is not yet well-known in Complementary and alternative medicine modern medicine; thus, the aim of the present review is to provide a critical appraisal of the current state of the Plant art regarding the ethnomedicinal uses, phytochemistry, and pharmacological properties of Tamarix spp. Materials and methods: Electronic databases (Medline, Cochrane library, Science Direct, and Scopus) were searched with the words “Tamarix” and “Tamarisk” to collect all available data regarding different Tamarix species from the inception until May 2019. Results: Tamarix spp. is traditionally used for gastrointestinal disorders, wounds, diabetes, and dental problems. Phenolic acids, flavonoids, and tannins constitute the main phytochemicals of these plants. Preclinical pharmacological evaluations have demonstrated several biological activities for Tamarix spp. including antidiabetic, hepatoprotective, wound healing, and anti-inflammatory; however, no clinical evidence have yet been provided to support the health benefits of these plants. Conclusions: Tamarix spp. are plants rich in polyphenolic compounds with valuable medicinal properties; though, there are several methodological problems such as lack of a mechanistic approach and taxonomic ambiguities in the current available data. High-quality preclinical studies, as well as well-designed clinical trials are necessary to confirm the safety and efficacy of these plants in humans.

1. Introduction phytochemical investigations on different Tamarix species which have introduced a series of phytochemicals amongst which the most im- The genus Tamarix from Tamaricaceae family, known with the portant ones are polyphenolic compounds; e.g. phenolic acids, flavo- common name of “Tamarisk” and “salt cedar”, consists of more than 60 noids, and tannins. Also, in different countries of Asia and Africa, such species of halophyte plants which are grown in nearly all parts of the as Pakistan, India, Iran, and Algeria in which tamarisk in naturally world. These plants are characterized with needlelike leaves which are grown, local people use this plant for medicinal purposes (Alnuqaydan covered with salt, secreted from the salt glands (Samadi et al., 2013). and Rah, 2019). In this paper, we provide a critical appraisal of the Tamarisk species are well-known for their growth in hot and dry cli- state of the art on the current available evidence regarding the tradi- mates; however, they are also found in temperate climates. (Zhang tional medicinal applications, phytochemistry, and pharmacological et al., 2002). Tamarix species are cultivated in dry climates in order to activities of different species of the genus Tamarix. fix the sand dunes (Han et al., 2013); whereas their growth in wet climates are not desired since they act as invasive plants which prevents the growth of other species (Whitcraft et al., 2007). There are several

∗ Corresponding author. Number 27, North Sarparast St., West Taleqani St., Felestine Sq., Postal Code: 1417653761, Tehran, Iran. E-mail address: [email protected] (R. Rahimi). https://doi.org/10.1016/j.jep.2019.112245 Received 26 June 2019; Received in revised form 15 September 2019; Accepted 16 September 2019 Available online 19 September 2019 0378-8741/ © 2019 Elsevier B.V. All rights reserved. R. Bahramsoltani, et al. Journal of Ethnopharmacology 246 (2020) 112245

Abbreviations LPO lipid peroxidation H2O2 hydrogen peroxide AD Alzheimer's diseases LDH lactate dehydrogenase NMDA receptor N-methyl-d-aspartate receptor GGT γ-glutamyl transpeptidase EtOH ethanol TNF tumor necrosis factor MeOH methanol COX cyclooxygenase FBS fasting blood sugar NF-κB nuclear factor-κB TC total cholesterol CAT catalase HDL-C high-density lipoprotein cholesterol Hb hemoglobin BW body weight MWM Morris-water maze GSH reduced glutathione Alb albumin AST aspartate transaminase ROS reactive oxygen species ALT alanine transaminase Aβ amyloid β ALP alkaline phosphatase hIAPP human islet amyloid polypeptide ALX alloxan Chk checkpoint kinase STZ streptozotocin Erk extracellular signal-regulated kinase

LD50 lethal dose 50% LPS lipopolysaccharide LC50 lethal concentration 50% MIC minimum inhibitory concentration CCl4 carbon tetrachloride NO nitric oxide ext extract iNOS inducible nitric oxide synthase Gpx glutathione peroxidase EtAc ethyl acetate GST glutathione-S-transferase JNK c-Jun N-terminal kinase XO xanthine oxidase MAPK Mitogen-activated protein kinase SOD superoxide dismutase

2. Methodology sandy or gravelly areas and on the river banks. In Unani medicine, it is known as Mayeen kalan (T. gallica L. and T. indica Willd.) and Mayeen Electronic databases including Medline, Cochrane library, Science khurd (T. pentandra Pall., T. gallica L.) (Quattrocchi, 2016); while in Direct, and Scopus were searched with the keywords “Tamarix” and Ayurveda, it is called as “Jhau” or “Jhavuka”. Several of Tamarix species “Tamarisk” to collect all published works about different Tamarix spe- such as T. ericoides Rottler & Willd. and T. dioica Roxb. ex Roth are also cies from the inception until May 2019. Primary included papers were mentioned to be used as mild laxative, antitussive, and antipyretic and screened by two independent investigators and relevant articles were are useful for the treatment of liver and spleen disorders (Quattrocchi, chosen to be checked based on the full-texts. All types of studies in- 2016). T. gallica is reported to be used in leucoderma, spleen disorders cluding ethnopharmacological studies, phytochemical analysis, in vitro and eye diseases (Shanna and Parmar, 1998). T. gallica also possesses assement of biological activities, and in vivo evaluations were included anti-inflammatory and wound healing properties and is used in uterine in this review. Additionally, the text books of traditional medicines of bleeding, leucorrhoea (Abdul Hakeem, 2002) and in the form of pessary countries in which tamarisk is natively grown such as Persian medicine for atony of vagina (Khare, 2004). Furthermore, decoction of its root and Indian medicine were also searched to extract the ancient medic- and leaf is used in sitz bath for treating leucorrhoea and anal prolapse inal uses of the plant. Studies in which the scientific names were not (Kabiruddin, 2000; Government of India, Ministry of Health and Family mentioned, as well as studies on the uses of Tamarix spp. in the fields Welfare, 2009). In topical form, T. indica (syn: T. troupii Hole) and T. other than medical sciences (e.g. agriculture and environmental sci- aphylla (L.) H.Karst. are used for skin disorders such as eczema and anal ences) were excluded. Results of the ethnopharmacological studies, fissure (Quattrocchi, 2016). T. aphylla (syn: T. articulata Vahl) is re- phytochemical analysis, and pharmacological evaluations were sum- ported to be an aphrodisiac (Nadkarni, 1976) and T. dioica is used for marized in Tables 1–3, respectively. Also, the quality of animal studies spermatorrhoea (Quattrocchi, 2016). was assessed according to Animal Research: Reporting of In Vivo Ex- Ethnopharmacological reports on different species of Tamarix are periments (ARRIVE) guidelines (McGrath and Lilley, 2015) which is summarized in Table 1. Most of these reports belongs to Pakistan in provided in Table 4. which tamarisk is used for a wide spectrum of infective diseases from simple cough and cold (Umair et al., 2019) to dental infections (Khalid et al., 2017) and severe infections such as tuberculosis, smallpox, and 3. Traditional and local medicinal use leprosy (Aslam et al., 2014). There are also several reports on the wound healing and antidiarrheal properties of the plant which can be Tamarix spp. is one of the plants known for its medicinal properties attributed to its high content of phenolic compounds with astringent in Persian Medicine. The plant was known as “Asl”, “Tarfā", and “Gaz” effects. Diabetes, liver and spleen problems, and rheumatism are other and the fruits were called “Gazmāzaj" or “Azbeh”. The plant was known indications of tamarisk reported in ethnopharmacological studies to have a cold and dry nature with astringent and cleansing effects on (Table 1). internal organs which was attributed to its bitter taste. It was known as a tonic for liver and spleen which was taken with vinegar or wine. It was believed that drinking water in a cup made of tamarisk wood can 4. Phytochemicals benefit patients with spleen diseases. Tamarisk was used as an antiulcer agent for both skin and gastrointestinal ulcers and an antihemorrhagic 4.1. Phenolic compounds for different types of bleeding like hemorrhoid and gastrointestinal bleedings in the form of decoction or infusion. It was also considered Polyphenolic compounds are an important category of phytochem- beneficial for loose and infected teeth (Khorasani, 1771; Razi, 2005; icals with well-established biological properties such as antioxidant, Avicenna, 1991). anti-inflammatory, anticancer, and antimicrobial effects (Rasouli et al., In India, Tamarix species are mainly found in northern parts in 2017). They are categorized under different subgroups such as

2 .Bhaslai tal. et Bahramsoltani, R.

Table 1 Ethnomedicinal uses of Tamarix spp. in different parts of the world

Plant species Location Parts used Indication Rout of administration/ Preparation Reference

T. africana Poir. Highland region of Bordj Bou Arreridj L Cardiovascular diseases, diuretics S/ Infusion (Miara et al., 2019) (Northeast Algeria) T. aphylla (L.) H.Karst. Rajhan Pur, Punjab, Pakistan R, L Tuberculosis, leprosy, smallpox, Jaundice, all contagious diseases ND (Aslam et al.) T. aphylla (L.) H.Karst. Chenab riverine area, Punjab L, B Febricity, wound & boils, eye infection, cough & cold S, Lo/ Poultice, paste, decoction, ash (Umair et al., 2019) province, Pakistan T. aphylla (L.) H.Karst. Karamar valley Swabi, Pakistan B Infection of gums and teeth, rheumatism, Jaundice ND (Khalid et al., 2017) T. aphylla (L.) H.Karst. District Karak, Pakistan L In animals: pain killer for open wounds, helpful in bird flu S/ Smoke (Khattak et al., 2015) T. aphylla (L.) H.Karst. Pakistan F Diabetes S/ Decoction (Yaseen et al., 2015) T. aphylla (L.) H.Karst. Jordan, North Badia L Fever S/ Decoction (Alzweiri et al., 2011) T. aphylla (L.) H.Karst. Peshawar valley, Pakistan B, L Wound healing and rheumatism, S, Lo/ Powder, extract (Bahadur et al., 2018) Tetanus, abdominal pain, paralysis T. aphylla (L.) H.Karst. Central Sahara Sh Postpartum care: aid to menstruation, fever S/ Decoction (Hammiche and Maiza, 2006) T. aphylla (L.) H.Karst. North Western Part (D.I. Khan) of Wp Jaundice, bad evils, rheumatism, wound & abscesses S, Lo/ Ash, decoction of the ash, (Ahmad et al., 2009)

3 Pakistan boiled leaves T. aphylla (L.) H.Karst. District Sargodha, B Aphrodisiac, measles S/ powdered with oil, smoke (Shah et al., 2015) Punjab, Pakistan T. aphylla (L.) H.Karst. Central region of Abyan governorate, B, L Hair fall, abdominal pain, asthma, cough S, Lo/ Infusion, decoction (Al-Fatimi, 2019) Yemen Tamarix aphylla (L.) H.Karst. (syn: T. South-eastern Morocco (Errachidia L Hypertension S/ Decoction (Tahraoui et al., 2007) articulata Vahl) province) T. dioica Roxb. ex Roth Chenab riverine area, Punjab L, B Pile, tonic, cough, diarrhea, antiseptic, spleen disorder and liver problems S/ Powder (Umair et al., 2019) province, Pakistan T. dioica Roxb. ex Roth Bhimber Azad Jammu & Kashmir, WP Anal-fisher, cough, diarrhea, dysentery, pectoral affection, piles, ulcer, S, Lo/ Smoke, fumigation, ointment (Mahmood et al., 2011) Pakistan leucorrhoea, spleen trouble, polio & tuberculosis, cold & flu T. dioica Roxb. ex Roth Peshawar valley, Pakistan B, L Wound healing, tetanus, abdominal pain of livestock i.e. sheep's, goats, S, Lo/ Powder, decoction (Bahadur et al., 2018) cow & buffalo T. gallica L. Central Sahara Sh, G Chills, cold, tonsillitis, sudorific, Eye diseases, boils, diarrhea S, Lo/ Decoction, poultice (Hammiche and Maiza,

2006) Journal ofEthnopharmacology246(2020)112245 T. indica Willd. Mera, district Charsadda, KP, Pakistan B Relieving wounds, skin fire burns, toothache Lo/ Powder mixed with oil (Ullah et al., 2014) T. ramosissima Ledeb. Zanjan province, Iran Sh Fungal skin scars, diarrhea S, Lo/ Decoction, oil from the (Moghanloo et al., 2019) burning branches

AbbreviationsT: Tamarix, R: root, L: leaf, B: bark, F: fruit, G: gall, WP: whole plant, SH: shoots, S: systemic, Lo: local, ND: not determined .Bhaslai tal. et Bahramsoltani, R. Table 2 Phytochemicals identified in Tamarix spp.

Phytochemical category Phytochemical name Species Part/ extract Reference

Alcohol Benzyl alcohol T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) Farnesol T. boveana Bunge Ap/ EO (Saidana et al., 2008) Phytol T. hispida Willd., T. boveana Bunge Ap/ Aq-acetone, EO (Saidana et al., 2008; Sultanova et al., 2004b) Tridecanol T. boveana Bunge Ap/ EO (Saidana et al., 2008) Hexadecanol T. boveana Bunge Ap/ EO (Saidana et al., 2008) n-Hentriacontan-12-ol T. canariensis Willd. L/ lipid (Basas-Jaumandreu et al., 2014) Aldehyde 2-methyl decanal T. boveana Bunge Ap/ EO (Saidana et al., 2008) 2,4-Nonadienal T. boveana Bunge Ap/ EO (Saidana et al., 2008) 3-hydroxy- 4-methoxycinnamaldehyde T. senegalensis DC. (syn: T. nilotica R/ Pet (Barakat et al., 1987) (isoferulaldehyde) (Ehrenb.) Bunge) 4-hydroxy-3-methoxycinnamaldehyde T. senegalensis DC. (syn: T. nilotica R/ Pet (Barakat et al., 1987) (ferulaldehyde) (Ehrenb.) Bunge) Benzeneacetaldehyde T. dioica Roxb. ex Roth F, L/ EO (Bughio et al., 2018) Nonanal T. boveana Bunge Ap/ EO (Saidana et al., 2008) Octanal T. boveana Bunge Ap/ EO (Saidana et al., 2008) Syringaldehyde T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) Vanillin T. boveana Bunge Ap/ EO (Saidana et al., 2008) Aromatic aldehyde 2-Hydroxy- Benzaldehyde T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) 2-Methyl- Benzaldehyde T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) Aromatic hydrocarbone 2,3-Dimethoxytoluene T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) Carbohydrate Arabinose T. mannifera (Ehrenb.) Bunge Gu (Maleki and Djazayeri, 1972) Fructose T. aphylla (L.) H.Karst. , T. mannifera G, Gu / EtAc (Ishak et al., 1972a; Maleki and (Ehrenb.) Bunge Djazayeri, 1972)

4 Glucose T. aphylla (L.) H.Karst. , T. mannifera G, Gu/ EtAc (Ishak et al., 1972a; Maleki and (Ehrenb.) Bunge Djazayeri, 1972) Mannose T. mannifera (Ehrenb.) Bunge Gu (Maleki and Djazayeri, 1972) Raffinose T. aphylla (L.) H.Karst. G/ EtAc (Ishak et al., 1972a) Ribose T. aphylla (L.) H.Karst. G/ EtAc (Ishak et al., 1972a) Sucrose T. aphylla (L.) H.Karst. G/ EtAc (Ishak et al., 1972a) Xylose T. aphylla (L.) H.Karst. , T. mannifera G, Gu/ EtAc (Ishak et al., 1972a; Maleki and (Ehrenb.) Bunge Djazayeri, 1972) Carboxilic acid Decanoic acids T. ramosissima Ledeb., T. boveana Bunge Ap, L, F/ EO (Bughio et al., 2018; Saidana et al., , T. dioica Roxb. ex Roth 2008) Succinic acid T. africana Poir. Sh/ MeOH (Karker et al., 2016) Hexanoic acid T. boveana Bunge Ap/ EO (Saidana et al., 2008) Heptanoic acid T. boveana Bunge Ap/ EO (Saidana et al., 2008) Laserine T. hampeana Boiss. & Heldr. F/ MeOH (Aykac and Akgul, 2010) Octanoic acid T. boveana Bunge Ap/ EO (Saidana et al., 2008) Journal ofEthnopharmacology246(2020)112245 Nonanoic acid T. boveana Bunge, T. dioica Roxb. ex Ap, L, F/ EO (Saidana et al., 2008), (Bughio et al., Roth 2018) Diterpene Manool T. boveana Bunge Ap/ EO (Saidana et al., 2008) Fatty acid ester Methyl palmitate T. boveana Bunge Ap/ EO (Saidana et al., 2008) Flavonoids 3,5,7-trihydroxy-3′,4′-dimethoxyflavone T. elongata Ledeb., T. laxa Willd. Ap/ EtAc & aqueous (Umbetova et al., 2005) 3,7,4′-trihydroxy-5-methoxyflavone T. elongata Ledeb., T. laxa Willd. Ap/ EtAc & aqueous (Umbetova et al., 2005) 4′,7-di-O-methylkaempferol-3-O-sulphate T. africana Poir. Sh/ MeOH (Karker et al., 2016) 5,2’,4’-trihydroxy-6,7,8- trimethoxyflavone T. dioica Roxb. ex Roth Ap/ Pet & Benzene (Parmar et al., 1994) (tamadone) 5,7,2’-trihydroxy-6,4’-dimethoxyflavone T. dioica Roxb. ex Roth Ap/ Pet & Benzene (Parmar et al., 1994) (tamaridone) 5,7,4′-trihydroxyflavan 7-O-sulphate T. africana Poir. Sh/ MeOH (Karker et al., 2016) 5,7,4′-trihydroxyflavan-4-ol 5,7-disulphate T. africana Poir. Sh/ MeOH (Karker et al., 2016) 7,3′,4′-trihydroxy-5-methoxyflavone T. elongata Ledeb., T. laxa Willd. Ap/ EtAc & aqueous (Umbetova et al., 2005) Apigenin (continued on next page) .Bhaslai tal. et Bahramsoltani, R. Table 2 (continued)

Phytochemical category Phytochemical name Species Part/ extract Reference

T. aphylla (L.) H.Karst., T. africana Poir., SS, L, B/ EtOH, Pet & (Mahfoudhi et al., 2014; Parmar T. ramosissima Ledeb. benzene et al., 1994, Ren et al., 2019) Chrysoeriol T. smyrnensis Bunge (Syn: T. hohenackeri Ap/ EtAc (Xing et al., 2014) Bunge) Cirsimaritin T. ramosissima Ledeb. B/ EtOH (Ren et al., 2019) Dillenetin T. smyrnensis Bunge (Syn: T. hohenackeri Ap/ EtAc (Xing et al., 2014) Bunge) Eriodictyol T. ramosissima Ledeb. B/ EtOH (Ren et al., 2019) Gardenin A-C T. africana Poir., T. dioica Roxb. ex Roth Sh/ MeOH, Pet & (Karker et al., 2016; Parmar et al., benzene 1994) Glycitein T. ramosissima Ledeb. B/ EtOH (Ren et al., 2019) Hesperetin T. ramosissima Ledeb. B/ EtOH (Ren et al., 2019) Hispidulin T. ramosissima Ledeb. B/ EtOH (Ren et al., 2019) Iso quercetin T. aphylla (L.) H.Karst. G/ EtAc (Ishak et al., 1972a) Iso rhamnetin T. aphylla (L.) H.Karst. , T. hispida L, S, B/ EtOH, aqueous (Baaka et al., 2017; Mahfoudhi et al., Willd., T. ramosissima Ledeb. 2014; Ren et al., 2019) Iso rhamnetin 3-O-β-glucopyranoside T. elongata Ledeb. T. laxa Willd. Ap/ EtAc & aqueous (Umbetova et al., 2005) Iso rhamnetin 7-O-sulfate T. elongata Ledeb, T. laxa Willd. Ap/ EtAc & aqueous (Umbetova et al., 2005) Juglanin T. aphylla (L.) H.Karst. G/ EtAc (Ishak et al., 1972a) Kaempferide T. nilotica (Ehrenb.) Bunge, T. aphylla Ap/ EtOH, aqueous (Baaka et al., 2017; Mahfoudhi et al., (L.) H.Karst. 2014; Orfali et al., 2009) Kaempferide 3-O-β-glucopyranoside T. elongata Ledeb. T. laxa Willd. Ap/ EtAc & aqueous (Umbetova et al., 2005) Kaempferol T. aphylla (L.) H.Karst., T. africana Poir. L & S/ MeOH, EtOH, (Baaka et al., 2017; Karker et al., aqueous 2016; Mahfoudhi et al., 2014) Kaempferol - 4’-7dimethyl ether-3-sulphate T. aphylla (L.) H.Karst. F/ EtOH (El Ansari et al., 1976)

5 Kaempferol 3,4'-dipotassium sulphate T. tetragyna Ehrenb. F/ Aq-EtOH (El-Mousallami et al., 2000) Kaempferol 3-O- sulphate-7,4’-dimethyl ether T. senegalensis DC. (syn: T. nilotica F/ Aq-acetone (Nawwar et al., 1984b) (Ehrenb.) Bunge) Kaempferol 3-O-β -D-glucuronopyranoside T. africana Poir. Sh/ MeOH (Karker et al., 2016) Kaempferol 3-O-β-D-glucuronic acid-ethyl T. senegalensis DC. (syn: T. nilotica F/ Aq-acetone (Nawwar et al., 1984b) ester (Ehrenb.) Bunge) Kaempferol 4'-methyl ether T. senegalensis DC. (syn: T. nilotica L/ n-BuOH (Abouzid et al., 2009) (Ehrenb.) Bunge) Kaempferol 7,4-dimethyl ether 3,5-di-O- T. senegalensis DC. (syn: T. nilotica F/ Aq-EtOH (El-Mousallami et al., 2000) SULFITE (Ehrenb.) Bunge) Kaempferol-4, 7-dimethyl ether T. senegalensis DC. (syn: T. nilotica L/ EtOH (El Sissi et al., 1973) (Ehrenb.) Bunge) Kaempferol-4', 7-dimethyl ether-3-glucoside T. senegalensis DC. (syn: T. nilotica L/ EtOH (El Sissi et al., 1973) (Ehrenb.) Bunge)

Kaempferol-5,7,4'-trimethyl ether T. aphylla (L.) H.Karst. F/ EtOH (Nawwar et al., 1975) Journal ofEthnopharmacology246(2020)112245 Kaempferol-7, 4′-dimethyl ether T. aphylla (L.) H.Karst., T. senegalensis L & S/ EtOH, aqueous (Baaka et al., 2017; Mahfoudhi et al., DC. (syn: T. nilotica (Ehrenb.) Bunge) 2014; Orfali et al., 2009) Kaempferol-7-monomethyl ether T. aphylla (L.) H.Karst. F/ EtOH (Nawwar et al., 1975) Kaempheride 3,7-dipotassium sulphate T. tetragyna Ehrenb. F/ Aq-EtOH (El-Mousallami et al., 2000) Kaempheride 3-O-β-glucuronide T. tetragyna Ehrenb. F/ Aq-EtOH (El-Mousallami et al., 2000) Kaempheride 3-potassium sulphate T. tetragyna Ehrenb. F/ Aq-EtOH (El-Mousallami et al., 2000) Luteolin T. aphylla (L.) H.Karst. L & S/ EtOH (Mahfoudhi et al., 2014) Monomethyl ether quercetin T. aphylla (L.) H.Karst. L/ Aqueous (Baaka et al., 2017) Naringenin T. africana Poir., T. senegalensis DC. Sh/ EtOH, MeOH (Karker et al., 2016; Orfali et al., (syn: T. nilotica (Ehrenb.) Bunge) 2009) Naringenin 4′-O-sulphate T. africana Poir. Sh/ MeOH (Karker et al., 2016) Nevadensin A T. dioica Roxb. ex Roth Ap/ Pet & Benzene (Parmar et al., 1994) Polymethyl ether quercetin T. aphylla (L.) H.Karst. L/ Aqueous (Baaka et al., 2017) Quercetin T. aphylla (L.) H.Karst., T. senegalensis SS, L/ EtOH (Mahfoudhi et al., 2014; Orfali et al., DC. (syn: T. nilotica (Ehrenb.) Bunge) 2009) (continued on next page) .Bhaslai tal. et Bahramsoltani, R. Table 2 (continued)

Phytochemical category Phytochemical name Species Part/ extract Reference

Quercetin-dimethyl-ether T. aphylla (L.) H.Karst. L & S/ EtOH (Mahfoudhi et al., 2014) Quercetin 3′,4′-dimethyl ether 3-O-sulfite T. tetragyna Ehrenb. F/ Aqueous alcohol (El-Mousallami et al., 2000) Quercetin 3-O-isoferulyl-glycoronide T. aphylla (L.) H.Karst. F/ EtOH (El Ansari et al., 1976) Quercetin 3-O-Potassium sulfite T. tetragyna Ehrenb. F/ Aq-EtOH (El-Mousallami et al., 2000) Quercetin 3-O-sulfate T. elongata Ledeb., T. laxa Willd. Ap/ EtAc & aqueous (Umbetova et al., 2005) Quercetin 3-O-β-D-glucupyranuronide T. senegalensis DC. (syn: T. nilotica L/ n-BuOH (Abouzid et al., 2009) (Ehrenb.) Bunge) Quercetin 3-O-β-D-glucuronide 6''-methy ester T. senegalensis DC. (syn: T. nilotica F/ Aq-acetone (Nawwar et al., 1984b) (Ehrenb.) Bunge) Quercetin 3-O-β-glucopyranoside T. elongata Ledeb., T. laxa Willd. Ap/ EtAc & aqueous (Umbetova et al., 2005) Quercetin 7,4′-dimethyl ether 3-O-sulfite T. tetragyna Ehrenb. F/ Aq-EtOH (El-Mousallami et al., 2000) Quercetin 7-methyl ether 3,3′,4′-tri-O-sulfite T. tetragyna Ehrenb. F/ Aq-EtOH (El-Mousallami et al., 2000) Quercetin dimethyl ether T. aphylla (L.) H.Karst. L/ Aqueous (Baaka et al., 2017) Quercetin-3-glucoside T. senegalensis DC. (syn: T. nilotica L/ EtOH (El Sissi et al., 1973) (Ehrenb.) Bunge) Quercetin-3-rhamnoside T. aphylla (L.) H.Karst. F/ EtOH (Nawwar et al., 1975) Quercetm 3-O-β-D-glucuronide 6"-ethyl ester T. senegalensis DC. (syn: T. nilotica F/ Aq-acetone (Nawwar et al., 1984b) (Ehrenb.) Bunge) Rhamnocitrin T. hispida Willd. Ap/ Aq-acetone (Sultanova et al., 2004a) Ramosissimin T. ramosissima Ledeb. Sh/ Aq-EtOH (Hong et al., 2018) Rhamnetin-3'-glucoronide-3,5,4'-trisulphate T. aphylla (L.) H.Karst. L/ Aq-EtOH (Saleh et al., 1975) Rhamnetin-3'-glucuronide-3, 5, 4'-trisulphate T. aphylla (L.) H.Karst. F/ EtOH (Nawwar et al., 1975) Tamarixetin T. senegalensis DC. (syn: T. nilotica L, S, G/ EtOH, EtAc, n- (Abouzid et al., 2009; Baaka et al., (Ehrenb.) Bunge), T. aphylla (L.) BuOH, aqueous 2017; Ishak et al., 1972b; Parmar H.Karst., T. indica Willd. (syn: T. troupii et al., 1985)(Mahfoudhi et al., 2014)

6 Hole) Tamarixetin 3,3'-di-sodium sulphate T. aphylla (L.) H.Karst. F/ Aq-MeOH (Nawwar et al., 2009) Tamarixetin 3-O-α-rhamnopyranoside T. elongata Ledeb., T. laxa Willd. Ap/ EtAc & aqueous (Umbetova et al., 2005) Tamarixetin-3-glucoside T. senegalensis DC. (syn: T. nilotica L/ EtOH (El Sissi et al., 1973) (Ehrenb.) Bunge) Tamarixin T. laxa Willd. Ap/ MeOH (Utkin, 1966) Tangeretin T. ramosissima Ledeb. B/ EtOH (Ren et al., 2019) Hydrocarbon Hentriacontanol T. hispida Willd. Ap/ Aqueous acetone (Sultanova et al., 2004b) Heneicosane T. boveana Bunge, T. dioica Roxb. ex Ap, L, F/ EO (Saidana et al., 2008)(Bughio et al., Roth 2018) Docosane- nonacosane T. boveana Bunge, T. dioica Roxb. ex Ap, L, F/ EO (Bughio et al., 2018; Saidana et al., Roth 2008) Tetradecane- nonadecane T. boveana Bunge, T. dioica Roxb. ex Ap, L, F/ EO (Bughio et al., 2018; Saidana et al., Roth 2008)

Ketone Vitispirane T. dioica Roxb. ex Roth F, L/ EO (Bughio et al., 2018) Journal ofEthnopharmacology246(2020)112245 Lactam Tamaractam T. ramosissima Ledeb. Ap/ Aq-EtOH (Yao et al., 2017) Lignan Coniferyl alcohol 4-O-sulphate T. senegalensis DC. (syn: T. nilotica L/ n-BuOH (Abouzid et al., 2009) (Ehrenb.) Bunge) Syringaresinol T. senegalensis DC. (syn: T. nilotica Debarked roots/ EtOH (Nawwar et al., 1982) (Ehrenb.) Bunge) Monolignol Eugenol T. boveana Bunge Ap/ EO (Saidana et al., 2008) Monoterpene Tricyclene T. boveana Bunge Ap/ EO (Saidana et al., 2008) Camphene T. boveana Bunge Ap/ EO (Saidana et al., 2008) Dihydroactinidiolide T. ramosissima Ledeb., T. dioica Roxb. ex Ap, L, F/ EO (Bughio et al., 2018 Roth Isocarveol T. boveana Bunge Ap/ EO (Saidana et al., 2008) Safranal T. dioica Roxb. ex Roth F, L/ EO (Bughio et al., 2018) β-damascenone T. dioica Roxb. ex Roth F, L/ EO (Bughio et al., 2018) β-lonone T. dioica Roxb. ex Roth F, L/ EO (Bughio et al., 2018) Trans-geranylacetone T. dioica Roxb. ex Roth F, L/ EO (Bughio et al., 2018) (continued on next page) .Bhaslai tal. et Bahramsoltani, R. Table 2 (continued)

Phytochemical category Phytochemical name Species Part/ extract Reference

Phenolic acid 1-(2,4,6-Trihydroxyphenyl)- 2-Pentanone T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) 1-(3-hydroxy-4-methoxyphenyl) Ethanone T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) 1-(4-Hydroxy-3,5-dimethoxyphenyl)- T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) Ethanone, 1-(4-hydroxy-3-methoxyphenyl)- Ethanone T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) 1,2,3-Trimethoxy-5-methyl- Benzene T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) 1,2,4-Trimethoxybenzene T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) 1,2-Benzenediol T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) 1,2-Dimethoxy-4-(1-methoxyethenyl) benzene T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) 1,2-Dimethoxy-4-(2-methoxyethenyl)benzene T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) 1'-decarboxydehydrodigallic acid T. aphylla (L.) H.Karst. B/ Aq-acetone (Souliman et al., 1991) 1-isoferulyl-3-pentacosanoylglycerol T. aphylla (L.) H.Karst. B/ Aq-acetone (Souliman et al., 1991) 2,3,7,8-tetrahydroxy [1]benzopyrano[5,4,3- T. senegalensis DC. (syn: T. nilotica F/ Aq-acetone (Nawwar and Souleman, 1984) cde][1]benzopyran-5,10-dione. (Ehrenb.) Bunge) 2,3-Dimethyl Phenol T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) 2,3-di-O-dehydrodigallicmono-carboxyl- T. tetragyna Ehrenb. Debarked heart wood (Hussein, 1997) (α,β)-4C1-glucopyranose 2,4,6-Triisopropyl- Phenol T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) 2,6,-bis-(3,5-dimethoxy-4-hydroxyphenyl)-3,7 T. aphylla (L.) H.Karst. B/ Aqueous acetone (Souliman et al., 1991) dioxabicyclo-[3,3,0] -octane 2,6-Dimethoxy- Phenol T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) 2,6-Dimethoxy-4-(2-propenyl)-)- Phenol T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) 2,6-Dimethyl Phenol T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) 2-Ethyl Phenol T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) 2-Ethyl-5-methyl- Phenol T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013)

7 2-Methoxy- Phenol T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) 2-Methoxy-4-methy Phenol T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) 2-Methoxy-4-vinylphenol T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) 2-Methyl Phenol T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) 3,4,5-Trimethoxybenzoic acid T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) 3,4,8,9,10-pentahydroxy-dibenzo-[b,d]pyran- T. senegalensis DC. (syn: T. nilotica F/ Aq-acetone (Nawwar and Souleman, 1984) 6-one (Ehrenb.) Bunge) 3,4-Dimethoxy- Phenol T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) 3′,5′-Dimethoxyacetophenone T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) 3-Hydroxy-2-methylbenzaldehyde T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) 3-Methyl-1,2-Benzenediol T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) 3-O-trans-Caffeoylisomyricadiol T. senegalensis DC. (syn: T. nilotica Ap/ EtOH (Orfali et al., 2009) (Ehrenb.) Bunge) 4-Hydroxy-3,5-O-dimethylbenzoic acid T. hispida Willd. Ap (Sultanova et al., 2002)

(syringic acid) Journal ofEthnopharmacology246(2020)112245 4-Methoxygallic acid methyl ester T. hispida Willd. Ap/ Aqueous acetone (Sultanova et al., 2004b) 4-methyl&hydroxy-7,8-dimethoxycoumarin T. indica Willd. (syn: T. troupii Hole) L/ EtOH (Parmar et al., 1985) (troupin) 4-Methyl-1,2-Benzenediol T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) 5-Hydroxy veratric acid T. africana Poir. Sh/ MeOH (Karker et al., 2016) 5-Hydroxy veratric acid methyl ester T. africana Poir. Sh/ MeOH (Karker et al., 2016) Caffeic acid T. aphylla (L.) H.Karst., T. hispida Willd. L & S/ EtOH (Mahfoudhi et al., 2014; Sultanova et al., 2004b) Coniferyl alcohol 4-sulphate T. gallica L. S, B/ MeOH (Tomás-Barberán et al., 1990) Dehydrodigallic acid T. aphylla (L.) H.Karst., T. senegalensis G, debarked root/ EtOH, (Ishak et al., 1972b; Nawwar et al., DC. (syn: T. nilotica (Ehrenb.) Bunge), EtAc 1982) T. hispida Willd. Dehydrodigallic acid dimetyl ester T. aphylla (L.) H.Karst. F/ Aq-MeOH (Nawwar et al., 2009) Dehydrogallic acid T. aphylla (L.) H.Karst. G/ EtAc (Ishak et al., 1972b) Dehydrotrigallic acid T. aphylla (L.) H.Karst. G/ Aqueous ethanolic (Nawwar et al., 1994) (continued on next page) .Bhaslai tal. et Bahramsoltani, R. Table 2 (continued)

Phytochemical category Phytochemical name Species Part/ extract Reference

Dihydrojuglone-5-glycoside T. aphylla (L.) H.Karst. G/ EtAc (Ishak et al., 1972a) Ellagic acid T. aphylla (L.) H.Karst., T. tetragyna G, debarked heart wood, (Ishak et al., 1972a)(Hussein, 1997; Ehrenb., T. senegalensis DC. (syn: T. L, S, F/ EtOH, EtAc Mahfoudhi et al., 2014; Nawwar nilotica (Ehrenb.) Bunge) , T. et al., 1982; Orfali et al., 2009; amplexicaulis Ehrenb, T. hispida Willd. Souleman et al., 1998; Sultanova et al., 2004b) Ellagic acid 3,3’-dimethyl ether 4-O-β-D- Ta. senegalensis DC. (syn: T. nilotica Debarked root/ EtOH (Nawwar et al., 1982) glucopyranoside (Ehrenb.) Bunge) Ellagic acid 3,3'-dimethyl ether T. tetragyna Ehrenb. Debarked heart wood (Hussein, 1997) Ellagic acid 3,3'-dimethylether-4-O-Potassium T. tetragyna Ehrenb. Debarked heart wood (Hussein, 1997) sulfite Ellagic acid 4,4'- dimethyl ether 3- T. amplexicaulis Ehrenb F (Souleman et al., 1998) potassium sulphate Ellagic acid 4,4′-dimethyl ether 3-O-sulfite T. tetragyna Ehrenb. F/ Aqueous alcohol (El-Mousallami et al., 2000) Ellagic acid 4,4'-dimethyl ether T. amplexicaulis Ehrenb F (Souleman et al., 1998) Ellagic acid-3-methyl ether T. senegalensis DC. (syn: T. nilotica Ap/ EtOH (Orfali et al., 2009) (Ehrenb.) Bunge) Ellagic acids T. aphylla (L.) H.Karst. L / Aqueous (Baaka et al., 2017) Ferulic acid T. africana Poir., T. amplexicaulis Sh, F, debarked heart (Hussein, 1997; Karker et al., 2016; Ehrenb, T. tetragyna Ehrenb. wood/ MeOH Souleman et al., 1998) Ferulic acid methyl ester T. africana Poir. Sh/ MeOH (Karker et al., 2016) Gallic acid T. aphylla (L.) H.Karst., L, debarked heart wood, (Baaka et al., 2017; Hussein, 1997) T. tetragyna Ehrenb., G, Ap, S, F, debarked (Ishak et al., 1972a; Jdey et al., 2017; T. gallica L., roots/ Aqueous, EtAc, Mahfoudhi et al., 2014; Nawwar T. senegalensis DC. (syn: T. nilotica EtOH et al., 1982)

8 (Ehrenb.) Bunge), (Souleman et al., 1998; Sultanova T. amplexicaulis Ehrenb, T. hispida et al., 2004b) Willd. Gallic acid 3-methyl ether T. amplexicaulis Ehrenb. F (Souleman et al., 1998) Gallic acid 3-methyl ether 5-potassium T. amplexicaulis Ehrenb. F (Souleman et al., 1998) sulphate Gallic acid 4-methyl ether T. tetragyna Ehrenb. Debarked heart wood (Hussein, 1997) Gallic acid 4-methyl ether T. amplexicaulis Ehrenb. F (Souleman et al., 1998) Hexacosyl-p- coumarate T. dioica Roxb. ex Roth Ap/ Pet & Benzene (Parmar et al., 1994) Isoferulic acid T. senegalensis DC. (syn: T. nilotica Debarked root, debarked (Nawwar et al., 1982)(Hussein, (Ehrenb.) Bunge), T. tetragyna Ehrenb., heart wood, G, F/ EtAc, 1997)(Ishak et al., 1972a; Souleman T. aphylla (L.) H.Karst., T. amplexicaulis EtOH et al., 1998) Ehrenb. Iso ferulic acid 3-potassium sulphate T. amplexicaulis Ehrenb. F (Souleman et al., 1998)

Isoferulic acid methyl ester T. senegalensis DC. (syn: T. nilotica Ap/ EtOH (Orfali et al., 2009) Journal ofEthnopharmacology246(2020)112245 (Ehrenb.) Bunge) Isoferulic acid 3-O-Sulfite T. tetragyna Ehrenb. F/ Aqueous alcohol (El-Mousallami et al., 2000) Methyl ferulate 3-O-sulphate T. senegalensis DC. (syn: T. nilotica L/ n-BuOH (Abouzid et al., 2009) (Ehrenb.) Bunge) Methyl gallate T. senegalensis DC. (syn: T. nilotica F/ Aq-acetone (Nawwar et al., 1984b) (Ehrenb.) Bunge) Methyl gallate 4-methyl ether T. senegalensis DC. (syn: T. nilotica F/ Aq-acetone (Nawwar et al., 1984b) (Ehrenb.) Bunge) N-trans-Feruloyltyramine T. senegalensis DC. (syn: T. nilotica Ap/ EtOH (Orfali et al., 2009) (Ehrenb.) Bunge) p-Coumaric acid T. aphylla (L.) H.Karst. L & S/ EtOH, aqueous (Baaka et al., 2017; Mahfoudhi et al., 2014) Phenol T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) Phenyl-5-hexyn-3-ol T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) Syringic acid (Baaka et al., 2017; Hussein, 1997) (continued on next page) .Bhaslai tal. et Bahramsoltani, R. Table 2 (continued)

Phytochemical category Phytochemical name Species Part/ extract Reference

T. aphylla (L.) H.Karst. , T. tetragyna L, debarked heart wood/ Ehrenb. Aqueous Syringic acid isomer T. aphylla (L.) H.Karst. L, S/ EtOH (Mahfoudhi et al., 2014) Vanillalacetone T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) Vanillin T. ramosissima Ledeb. Wood/ EtOH (Xiao et al., 2013) Phenolic glyceride Niloticol I-feruloyl-3 pentauxanoyiglycerol T. senegalensis DC. (syn: T. nilotica R/ Pet (Barakat et al., 1987) (Ehrenb.) Bunge) Phenolic glycoside Dehydrodigallic acid xanthone T. aphylla (L.) H.Karst. G/ Aq-EtOH (Nawwar et al., 1994) Isoferulic acid 3-O-beta-glucopyranoside T. aphylla (L.) H.Karst. F/ Aq-MeOH (Nawwar et al., 2009) Phenolic lipid 5-n-Alkylresorcinol T. canariensis Willd. L/ lipid (Basas-Jaumandreu et al., 2014) Sesquiterpene α-bisabolol T. boveana Bunge Ap/ EO (Saidana et al., 2008) α-copaene T. boveana Bunge Ap/ EO (Saidana et al., 2008) α- & δ-cadinol T. boveana Bunge Ap/ EO (Saidana et al., 2008) β-cubebene T. boveana Bunge Ap/ EO (Saidana et al., 2008) β-caryophyllene T. boveana Bunge Ap/ EO (Saidana et al., 2008) γ-elemene T. boveana Bunge Ap/ EO (Saidana et al., 2008) γ-cadinene T. boveana Bunge Ap/ EO (Saidana et al., 2008) Alloaromadendrene T. boveana Bunge Ap/ EO (Saidana et al., 2008) Germacrene B & D T. boveana Bunge Ap/ EO (Saidana et al., 2008) Nerolidol T. boveana Bunge Ap/ EO (Saidana et al., 2008) Sterol Avenasterol T. gallica L. Ap/ Pet (Andhiwal et al., 1982) Cholesterol T. gallica L. Ap/ Pet (Andhiwal et al., 1982) Stigmasterol T. gallica L. Ap/ Pet (Andhiwal et al., 1982) 19-hexacontatetranol T. hampeana Boiss. & Heldr. F/ MeOH (Aykac and Akgul, 2010) 24-ethel-22-dehydrocholestanol T. gallica L. Ap/ Pet (Andhiwal et al., 1982)

9 24-ethylcholestanol T. gallica L. Ap/ Pet (Andhiwal et al., 1982) 24-ethyllathostrol T. gallica L. Ap/ Pet (Andhiwal et al., 1982) 24-methylcholestrol T. gallica L. Ap/ Pet (Andhiwal et al., 1982) 24-methylcholestenol T. gallica L. Ap/ Pet (Andhiwal et al., 1982) Tannin 1,2,6-tri-O-galloyl-β-D-glucose T. senegalensis DC. (syn: T. nilotica L/ Aq-acetone (Orabi et al., 2010a) (Ehrenb.) Bunge) 1,3-di-O-galloyl-4,6-O-(S)- T. senegalensis DC. (syn: T. nilotica L/ Aq-acetone (Orabi et al., 2009) hexahydroxydiphenoyl-β-D-glucose (Ehrenb.) Bunge) 2,6-digalioyl glucose T. aphylla (L.) H.Karst. G/ Aq-EtOH (Nawwar and Hussein, 1994) 2,3-digalloyl-D-glucopyranose (nilocitin) T. senegalensis DC. (syn: T. nilotica F/ Aq-acetone (Nawwar et al., 1984a) (Ehrenb.) Bunge) 2-O-Galloyl-3-O-(1-dehydrodigalloyl)-4,6- T. hispida Willd. Ap/ Aqueous acetone (Sultanova et al., 2004b) hexahydroxydiphenoylglucopyranose 3,6-digalloyl glucose T. aphylla (L.) H.Karst. G/ Aq-EtOH (Nawwar and Hussein, 1994) 4

2-O-Galloyl-(α/β)- C1- glucopyranose T. tetragyna Ehrenb. F/ Aq-EtOH (El-Mousallami et al., 2000) Journal ofEthnopharmacology246(2020)112245 2-O-galloyl-3-O-(3,4,5,6,7-pentahydroxybi- T. aphylla (L.) H.Karst. G/ Aq-EtOH (Nawwar et al., 1994) phenyl ether-8,-carboxylic acid-l- carboxyloyl)- 4,6-(S)- hexahydroxybiphenoyl- 4 (α/β)- C1-glucopyranose (Tamarixellagic acid) 2-O-Galloyl-D-glucopyranose T. hispida Willd. Ap/ Aqueous acetone (Sultanova et al., 2004b) Gemin D T. senegalensis DC. (syn: T. nilotica L/ Aqueous acetone (Orabi et al., 2009) (Ehrenb.) Bunge) Hippomanin A T. senegalensis DC. (syn: T. nilotica L/ Aqueous acetone (Orabi et al., 2009) (Ehrenb.) Bunge) Hirtellin T2 T. pakistanica Qaiser L/ n-BuOH (Ahmed et al., 1994) Hirtellin T3 T. pakistanica Qaiser L/ n-BuOH (Ahmed et al., 1994) Hirtellin A T. senegalensis DC. (syn: T. nilotica L, Callus & Sh cultures of (Orabi et al., 2009; Orabi et al., (Ehrenb.) Bunge) , T. tetrandra Pall. ex S, F/ Aq-acetone, EtAc, 2010a)(Orabi et al., 2011; Yoshida M.Bieb., T. pakistanica Qaiser Acetone et al., 1991) (continued on next page) .Bhaslai tal. et Bahramsoltani, R. Table 2 (continued)

Phytochemical category Phytochemical name Species Part/ extract Reference

Hirtellin B T. tetrandra Pall. ex M.Bieb. Callus & Sh cultures of S/ (Orabi et al., 2011; Orabi et al., Acetone 2010a) Hirtellin C T. tetrandra Pall. ex M.Bieb. Callus & Sh cultures of S/ (Orabi et al., 2011; Orabi et al., Acetone 2010a) Hirtellin F T. senegalensis DC. (syn: T. nilotica L/ Aqueous acetone (Orabi et al., 2010a) (Ehrenb.) Bunge) Hirtellin Q1 T. tetrandra Pall. ex M.Bieb. Callus & Sh cultures of S/ (Orabi et al., 2011) Acetone Hirtellin T1 T. tetrandra Pall. ex M.Bieb. Callus & Sh cultures of S/ (Orabi et al., 2011) Acetone Hirtellin T2 T. senegalensis DC. (syn: T. nilotica L/ Aq-acetone (Orabi et al., 2013) (Ehrenb.) Bunge) Isohirtellin C T. senegalensis DC. (syn: T. nilotica L, Callus & Sh cultures of (Orabi et al., 2011; Orabi et al., (Ehrenb.) Bunge), T. tetrandra Pall. ex S/ Acetone, Aq-acetone 2010a) M.Bieb. Nilotinin D1-D10, M1-M7, T1 T. senegalensis DC. (syn: T. nilotica L/ Aq-acetone (Orabi et al., 2013; Orabi et al., (Ehrenb.) Bunge) 2010b) Phyllagallin D1-D4, M1-M2 T. aphylla (L.) H.Karst. G/ Aq-acetone (Orabi et al., 2015) Remurin A T. senegalensis DC. (syn: T. nilotica L, Callus & Sh cultures of (Orabi et al., 2009) (Ehrenb.) Bunge) S /Aq-acetone, acetone Remurin B T. senegalensis DC. (syn: T. nilotica L/Aq-acetone (Orabi et al., 2009) (Ehrenb.) Bunge) Tamarixellagic acid T. aphylla (L.) H.Karst. G/ Aq-EtOH (Nawwar et al., 1994) Tamarixinin B T. pakistanica Qaiser , T. tetrandra Pall. F, Callus & Sh cultures of (Orabi et al., 2011; Yoshida et al., ex M.Bieb. S/ Acetone, EtAc 1993) 10 Tamarixinin C T. pakistanica Qaiser , T. tetrandra Pall. F, Callus & Sh cultures of (Orabi et al., 2011; Yoshida et al., ex M.Bieb. S/ Acetone, EtAc 1993) Tamarixinin A T. senegalensis DC. (syn: T. nilotica L, F/ EtAc, Aq-acetone (Orabi et al., 2010a; Yoshida et al., (Ehrenb.) Bunge), T. pakistanica Qaiser 1991) Tellimagrandin I T. tetrandra Pall. ex M.Bieb., T. Callus & Sh cultures of S, (Orabi et al., 2011; Orabi et al., senegalensis DC. (syn: T. nilotica L / Aq-acetone, Aq-EtOH 2010a) (Ehrenb.) Bunge) Tellimagrandin II T. nilotica (Ehrenb.) Bunge, T. tetrandra L, F, Callus & Sh cultures (Orabi et al., 2011; Orabi et al., Pall. ex M.Bieb., T. pakistanica Qaiser of S/ Aq-EtOH, aqueous 2010a; Yoshida et al., 1991) acetone Tetraterpene β-Carotene T. hispida Willd. Ap/ Aq-acetone (Sultanova et al., 2004b) Triterpenes 3α-(3'',4''-dihydroxy-trans-cinnamoyl oxy)-D- T. senegalensis DC. (syn: T. nilotica L/ n-Hexane (Abouzid et al., 2009) friedoolean-14-en-28-oic acid (Ehrenb.) Bunge) 3α-(3'',4''-dihydroxy-trans-cin-namoyloxy)-D- T. hispida Willd. Ap/ Aq-acetone (Sultanova et al., 2004a)

friedoolean-14-en-28oic acid Journal ofEthnopharmacology246(2020)112245 3-α-[3'', 4''-dihydroxy-trans-cinnamoyloxy]-D- T. hispida Willd. Ap/ EtOH (Sultanova et al., 2013) friedoolean-14-en-28-oic acids (isotamarixen) 3-α-[3'',4''-dihydroxy-trans-cinnamoyloxy]-D- T. hispida Willd., T. ramosissima Ledeb., Ap /EtOH (Sultanova et al., 2013) friedoolean-14-en-28-oic acids (isotamarixen) Т. еlongatа Ledeb. 3-α-[3″,4′-dihydroxytrans-cinnamoyl]-oxy-D- T. elongata Ledeb., Ap/ EtAc & aqueous (Umbetova et al., 2006) fridoolean-14-en-28-oic acid T. laxa Willd. 3-α-[4''-dihydroxy-trans-cinnamoyloxy]- T. hispida Willd., T. ramosissima Ledeb., Ap/ EtOH (Sultanova et al., 2013) Dfriedoolean -14-en-28-oic acid Т. elongata Ledeb. 3-α-hydroxy-D-friedoolean-14-en-28-oic acid Т. laxa Ap/ EtOH (Sultanova et al., 2013) 3β-al-D- friedoolean-14-en-28-oic acid methyl Т. laxa Ap/ EtOH (Sultanova et al., 2013) ether Lupeol T. indica Willd. (syn: T. troupii Hole) L/ EtOH (Parmar et al., 1985) o-friedoolean-l4en-3u,28-diol ( isomyricadiol) T. aphylla (L.) H.Karst. B/ CHCl3 (Merfort et al., 1992) Pentacyclic triterpenoid T. senegalensis DC. (syn: T. nilotica L/ n-BuOH (Abouzid et al., 2009) (Ehrenb.) Bunge) (continued on next page) R. Bahramsoltani, et al. Journal of Ethnopharmacology 246 (2020) 112245

flavonoids, tannins, phenolic acids, and lignans. Fig. 1 shows the structure of the most important tamarisk phytochemicals. Polyphenols are the most important and diverse phytochemicals identified in Ta- marix spp. which are described as follow: Sultanova et al., Sultanova et al., 4.1.1. Flavonoids Flavonoids are one of the most abundant polyphenols in human diet and are classified into six subgroups of flavonols, flavanols, flavanones, Umbetova et al., 2006 ) flavones, anthocyanins, and isoflavones (Pandey and Rizvi, 2009). A considerable number of flavonoids have been isolated from different Reference ( Umbetova et al., 2006 ) ( Parmar et al., 1985 ; 2013 ) ( Parmar et al., 1985 ) ( Parmar et al., 1985 ; 2004b ; Tamarix species (Table 2). Most of the Tamarix flavonoids have flavonol structure, i.e. they have a fixed 3-hydroxyflavone structure; whereas the presence of other flavonoid structures like flavanones such asnar- ingenin seems to be limited. Quercetin is a famous flavonol in several foods and vegetables of human diet which is also widely detected in the form of various glycosides in several Tamarix species. Tamarixetin, another flavonoid aglycone which itself is a derivative of quercetin (4′- methoxyquercetin) is named based on this plant genus and is so far identified in eight Tamarix species as aglycone and different glycoside forms. Also, rhamnetin, another flavonol, is found in several Tamarix species with different glycosylation patterns. Part/ extract Ap/EtAc & aqueous Ap /EtOH L/ EtOH L, Ap/ EtAc, EtOH, & aqueous 4.1.2. Phenolic acids Phenolic acids comprise a subgroup of organic acids with phenolic functional groups which are usually categorized under three classes of hydroxybenzoic acids, hydroxycinnamic acids, and aldehyde deriva-

T. tives (Robbins, 2003). Tamarix species contain several phenolic acids with all three structures. Nearly all parts of these plants contain phe- Hole) nolic acids; however, their identification is more dominant in wooden Hole) Willd. Willd. , T. parts (Table 2). Caffeic acid, ellagic acid, ferulic acid, gallic acid, p- Willd. (syn:

T. troupii coumaric acid, and syringic acid are well-known phenolic acids with Ledeb. , Tamarix T. troupii

Willd. , T. ramosissima previously demonstrated pharmacological and biological activities which are widely found in Tamarix spp. and thus, can play a role in Ledeb. , T. laxa Ledeb. , T. laxa tamarisk therapeutic properties. Willd. (syn: Willd. , T. indica Hole) Willd. (syn: 4.1.3. Tannins Species T. elongata Т. laxa, T. hispida Ledeb. , Т. elongata indica T. indica T. elongata hispida troupii Tannins are another subcategory of phenolic compounds which are mostly known due to their astringent effects because of their properties to make complex with proteins. They are mainly classified into hydrolysable tannins, i.e. gallic acid and ellagic acid derivatives, as well as condensed tannins or the so called proanthocyanidins which include polymers of flavan-3-ol (de Jesus et al., 2012). In Tamarix spp., tannins have mostly been isolated from aqueous, hydroalcoholic, or aqueous- acetone extracts of the plant. Both gallotannins and ellagitannins are found in this genus; however, ellagitanins seem to be more prevalent (Table 2). Hirtellins and tamarixinins which are polymeric ellagitanins are widely found in aerial parts, as well as callus of the stems and shoots of different Tamarix species. Additionally, more complex structures such as the gallo-ellagitannins which comprise both gallotannins and ellagitannins are isolated from the galls of Tamarix spp. (Orabi et al., 2011, Orabi et al., 2015).

4.2. Terpenes Phytochemical name Taraxeran-14-ene-type triterpenoids methyl 3- β -al- D -fridoolean-14-en-28-oate Ursolic acid β -amyrin β -sitosterol Terpenes are a group of secondary metabolites in plants which consist of one or more isoprene subunits. Low molecular weight terpenes (mono-, sesqui- and diterpenes) are volatile compounds mostly found in the essential oil-bearing plants and are responsible for the aroma of these plants; whereas triterpenes which have higher molecular weights are usually non-volatile and are mostly extracted with non- polar solvents (Dudareva et al., 2004). Tamarix spp. contain a series of triterpenes and triterpenoids amongst which the most well-known ones are β-sitosterol, β-amyrin, and ursolic acid. Some volatile monoterpenes ( continued ) such as safranal, isocarveol, and camphene, along with sesquiterpenes like α-bisabolol and β-caryophyllene are also reported in the essential Phytochemical category

Table 2 AbbreviationsAq.: aqueous, EtOH: ethanol, MeOH: methanoL.R: EtAc: root. ethyl acetate, CHCl3: three chloromethane, L: leaves, S: stem, F: flower, B: bark, Sh: Shoot, Ap: aerial parts, Pet: petroleum, EO: essential oil, Gu: gum, oils of T. ramosissima Ledeb., T. dioica, and T. boveana Bunge. It should

11 R. Bahramsoltani, et al. Journal of Ethnopharmacology 246 (2020) 112245

Table 3 Pharmacological activities of Tamarix spp.

Pharmacological activity Plant species Part/ extract Model Dosage or concentration Results Reference

Anti-Alzheimer T. gallica L. Aerial parts/ In vivo: 100, 300 mg/kg/day ↓Spatial memory impairment, (Salissou et al., 2018) hyrometha- Homocysteine- ↓LPO, TNF-α, IL-1β, tau nolic ext induced hyperphosphorylation, Aβ Alzheimer's disease production, in rats followed by ↑SOD activity, MWM Improvement in structure & morphology of neurons Ten isolated Aerial parts/ In vitro: Aβ & 1, 10, 100 μM ↓Protein aggregation with a higher (Ben Hmidene et al., flavonoids hydroetha- hIAPP aggregation activity by the flavonoids containing 2017a) from T. nolic ext catechol moiety, gallica L. ↑SOD activity with the highest activity by tamarixetin, quercetin glucuronide & quercetin glucuronide methyl ester Anticholinesterase T. aphylla Leaf, stem/ In vitro: 1-1000 μg/ml Inhibition of acetylcholinesterase but (Mahfoudhi et al., 2016) (L.) H.Karst. several exts Acetylcholinestera- not butyrylcholinesterase se & butyrylcholinesterase inhibitory assay Antidiabetic T. aphylla Leaf/ MeOH In vivo: Normal & 100, 250, 400 mg/kg/ ↓FBS, HbA1c, (Ullah et al., 2017) (L.) H.Karst. STZ day ↑Hb +nicotinamide- induced diabetes in rats T. aphylla Leaf, stem/ In vitro: α- 1-1000 μg/ml Inhibition of α-glucosidase, with (Mahfoudhi et al., 2016) (L.) H.Karst. several exts glucosidase MeOH ext being the most active one inhibitory assay T. aphylla Aerial parts/ In vivo: STZ- 5 mg/kg/day ↓FBS, (Hebi et al., 2017b) (L.) H.Karst. Aqueous ext induced diabetes in ↑glucose tolerance, (syn: T. rats Improvement in histology of liver & articulata pancreas, Vahl) No significant change in BW T. aphylla Aerial parts/ In vivo: Normal & 5 mg/kg/day ↓FBS, TC, TAG, (Chaturvedi et al., 2012) (L.) H.Karst. flavonoid- STZ-induced ↑glucose tolerance, HDL-C (syn: T. rich ext diabetes in rats articulata Vahl) T. gallica L. Aerial parts/ In vitro: Inhibitory 1- 100 μM Inhibition of sucrase and maltase up (Ben Hmidene et al., purified activity on α- to 62.5% 2017b) flavonoids glucosidase from activity hydroethanolic ext T. articulata Aerial parts/ In vivo: Normal & 5 mg/kg/day ↓FBS, TC, TAG, (Hebi et al., 2018) Vahl flavonoid- STZ-induced ↑HDL-C, rich ext diabetes in rats ↓FBS in oral glucose tolerance test Antidiarrheal T. indica Leaf/ MeOH In vivo: Castor oil- 500 mg/kg/day Inhibition of diarrhea (Habiba et al., 2010) Willd. ext induced diarrhea in mice Antihyperlipidemic T. aphylla Aerial parts/ In vivo: Normal & 5 mg/kg/day ↑HDL-C, (Hebi and Eddouks, (L.) H.Karst. Aqueous ext STZ-induced ↓TC, TAG 2017a) (syn: T. diabetes in rats articulata Vahl) Anti-inflammatory T. aphylla Aerial parts/ In vivo: 100 mg/kg/day No significant effect on paw edema, (Qadir et al., 2014) (L.) H.Karst. hydroetha- Carrageenan- Antipyretic effects nolic ext induced paw edema & yeast- induced pyrexia in mice T. aphylla Leaf/ EtOH In vivo: 15%, 25% in gel base ↓Paw edema (Yusufoglu and (L.) H.Karst. Carrageenan- Alqasoumi, 2011) induced paw edema in rats T. gallica L. Aerial parts/ In vivo: 100, 200, 300 mg/kg/ ↓Edema in both models (Chaturvedi et al., 2012) MeOH Carrageenan- and day histamine-induced hind paw edema in rats T. smyrnensis Aerial parts/ In vitro: LPS- 0.1-100 μg/ml ↓NO release, gene transcription of (Chen et al., 2018) Bunge (Syn: four exts activated microglia iNOS, TNF-α, IL-1β, IL-6, T. cells (BV-2) Involvement of NF-κB signaling, w hohenackeri ith EtAc ext being the most active one (continued on next page)

12 R. Bahramsoltani, et al. Journal of Ethnopharmacology 246 (2020) 112245

Table 3 (continued)

Pharmacological activity Plant species Part/ extract Model Dosage or concentration Results Reference

Bunge) & four of the isolated compounds T. indica Root/ In vivo: 200, 400 mg/kg/day ↓Paw edema (Rahman et al., 2011) Willd. hyrometha- Carrageenan- nolic induced paw edema in rats Antimicrobial T. aphylla Leaf, stem, In vitro: Agar well 1 mg/ml Inhibition zones: 8.2-25.3 mm, (Khalid et al., 2017) (L.) H.Karst. bark/ diffusion method, ↓biofilm formation up to 75% of several exts micro-titer assay, control group, against 19 biofilm- Biofilm washing activity up to 78%, forming oral with strongest activity by the bark bacteria ext T. aphylla Leaf/ In vitro: 0.86-30 mg/ ml No significant antibacterial activity, (Muhammad et al., 2017) (L.) H.Karst. hydrometha- Antibacterial Antifungal activity with 54-70% of nolic ext activity against growth inhibition Escherichia coli & Staphylococcus aureus, Agar dilution method against three Aspergillus species T. Aerial parts/ In vitro: Agar well 100 mg/ml Inhibition zones: 8.2-13.7 mm (Mandeel and Taha, senegalensis EtOH ext & diffusion method 2005) DC. (syn: T. several sub- using seven fungal arabica exts species Bunge) T. Aerial parts/ In vitro: Agar 1.9- 500 μg/ ml MICs: 62.5- 250 μg/ ml for different (Benmerache et al., 2017) amplexicaulis hydrometha- dilution method isolated polyphenols Ehrenb. nolic ext against five (syn: T. bacteria balansae J.Gay) T. boveana Aerial parts/ In vitro: Agar disc 0.3-1 mg/ ml Inhibition zones: 0-8 mm, (Saidana et al., 2008) Bunge essential oil diffusion method No antibacterial effect against obtained by against six Gram + Pseudomonas aeruginosa steam and Gram - distillation bacteria T. dioica Flower & In vitro: Disc 10-1000 μg/ml MICs: 10-100 μg/ml, (Bughio et al., 2018) Roxb. ex leaf/ diffusion method Inhibition zones: 2-16 mm Roth essential oil using Staphylococcus aureus & Escherichia coli T. dioica Aerial parts/ In vitro: 7.8-500 μg/ ml MBC > 500 μg/ ml (Zaidi et al., 2012) Roxb. ex hydroetha- Bactericidal effects Roth nolic ext against clinical isolates and standard Helicobacter pylori T. dioica Aerial parts/ In vitro: Broth Serial two-fold dilutions Antibacterial activity: (Keymanesh et al., 2009) Roxb. ex hydroetha- microdilution from 10 mg/ ml MICs: 333.3-1333.3, Roth nolic ext method against 6 concentration Antifungal activity: bacterial and 3 MICs: 250- 500 μg/ ml, fungal species Not good antimicrobial activity T. dioica Leaf/ In vitro: Agar well 10 mg/ml Inhibition zones: (Khan et al., 2013) Roxb. ex different diffusion method Bacteria: 5-32 mm Roth fractions of against 7 bacterial Fungi: 7-30 mm, the and 5 fungal MICs: hydroetha- species Bacteria: 1.25-10 mg/ml, nolic ext Fungi: 0.312-10 mg/ml, MB(F)Cs: Bacteria: 2.5-10 mg/ml, Fungi: 0.625-10 mg/ml T. gallica L. Leaf & In vitro: Agar well 2-100 mg/ml Inhibition zones: (Ksouri et al., 2009) flower/ diffusion method Bacteria: 6-13 mm, MeOH ext against 5 bacterial Fungi: 6-9 mm & 5 Candida species T. gallica L. Aerial parts/ In vitro: Disc 0.25-8 mg/ml Inhibition zones: (Lefahal et al., 2010) n-butanol diffusion method Bacteria: 7.5-14.5 mm, fraction against 5 bacterial Fungi: 7.5-8 mm & 1 fungal species (continued on next page)

13 R. Bahramsoltani, et al. Journal of Ethnopharmacology 246 (2020) 112245

Table 3 (continued)

Pharmacological activity Plant species Part/ extract Model Dosage or concentration Results Reference

hydromethanolic ext T. indica Root/ In vitro: Disc 200 mg/disc Inhibition zones: 10.76-16.34 mm (Rahman et al., 2011) Willd. hyrometha- diffusion method nolic against 6 bacterial species T. Stem/ In vitro: Broth 31.3-4000 μg/ml for MICs: (Mohieldin et al., 2017) senegalensis MeOH, dilution method MIC, MeOH: 2 mg/ml, DC. (syn: T. hydroetha- using 10, 100 μg/ml for Hydroethanolic: 4 mg/ml, nilotica nolic ext Porphyromonas collagenase test Inhibition of collagenase activity (Ehrenb.) gingivalis Bunge) (Coykendall et al., 1980) Shah and Collins, 1988, Inhibition of collagenase activity assay T. Aerial parts/ In vitro: End point 1000 μg/ ml Virucidal activity against herpes (Soltan and Zaki, 2009) senegalensis hydroetha- titration technique simplex-1 virus DC. (syn: T. nolic ext against herpes nilotica simplex-1 virus, (Ehrenb.) poliomyelitis-1 Bunge) virus, and vesicular stomatitis virus T. Aerial In vitro: Well 5 mg/ ml Inhibition zones: 8-12 mm (Awaad et al., 2014) senegalensis flowering diffusion method DC. (syn: T. parts/ EtOH against 11 nilotica ext bacterial and 5 (Ehrenb.) fungal species Bunge) T. Leaf/ water: In vitro: Broth Antibacterial activity: Antibacterial activity: MICs: 12.5- (Sultanova et al., 2001) ramosissima acetone ext dilution method 12.5-100 μg/ ml, 100 μg/ ml, Ledeb. and agar tube Antifungal activity: 400 Antifungal activity: 14-75% of dilution method μg/ ml growth inhibition for bactericidal and antifungal activity against 15 microorganisms T. Bark/ In vitro: Disc 1-25 mg/ ml Antibacterial activity: (Ren et al., 2019) ramosissima ethanolic diffusion method MICs: 5-10 mg/ ml, Ledeb. extract against 7 bacterial MBCs: 10-25 mg/ ml with a better and 4 fungal effect on Gram-positive bacteria, species No significant antifungal activity Antinociceptive T. aphylla Aerial parts/ In vivo: Acetic acid- 100 mg/kg/day ↑Writhing inhibition, (Qadir et al., 2014) (L.) H.Karst. hydroetha- induced writhing, ↓paw licking, nolic ext hot plate test, & ↑reaction time in hot plate formalin-induced paw licking in mice T. gallica L. Aerial parts/ In vivo: Tail flick, 100, 200, 300 mg/kg/ ↑Pain threshold (Chaturvedi et al., 2012) MeOH ext hot plate, & acetic day acid-induced writhing in mice T. indica Leaf/ MeOH In vivo: Acetic acid- 500 mg/kg/day ↑Writhing inhibition (Habiba et al., 2010) Willd. ext induced writhing in mice T. indica Root/ In vivo: Acetic acid- 250, 500 mg/kg/day ↑Writhing inhibition (Rahman et al., 2011) Willd. hyrometha- induced writhing nolic in mice

Antioxidant T. gallica L. Shoots/ In vitro:H2O2- 0.01-50 μg/ ml ↑Cell viability, (Bettaib et al., 2017) hydroetha- induced oxidative Normalizing CAT activity, nolic ext stress in human ↓LPO, intestinal epithelial Regulation of JNK/ MAPK pathways (IEC-16) cells T. Flower/ In vivo: ALX- 100 mg/kg/day ↑GSH (Abouzid and Sleem, senegalensis hydroetha- induced diabetes in 2011) DC. (syn: T. nolic ext rats nilotica (Ehrenb.) Bunge) Anti-platelet activity T. smyrnensis Aerial parts/ In vitro: ACE 5- 100 mg/ ml Inhibition of ACE & platelet (Xing et al., 2014) Bunge (Syn: different inhibitory & aggregation mostly by flavonoids & T. fractions of platelet inhibitory phenolic compounds hohenackeri hydroetha- activity Bunge) nolic ext Antiprotease T. gallica L. Several concentrations (Jedinak et al., 2010) (continued on next page)

14 R. Bahramsoltani, et al. Journal of Ethnopharmacology 246 (2020) 112245

Table 3 (continued)

Pharmacological activity Plant species Part/ extract Model Dosage or concentration Results Reference

Leaf & bark/ In vitro: inhibitory IC50 for trypsin= 5.3 (leaf) & 1.7 hydrometha- activity on trypsin/ (bark) μg/ ml, nolic ext thrombin/ No inhibitory activity on thrombin & urokinase urokinase Antirheumatoid T. Tamaractam In vitro: Human 0.01-10 μM ↓Cell viability, (Yao et al., 2017) ramosissima isolated fibroblast-like ↑apoptosis via activation of caspase Ledeb. form aerial synoviocytes from 3/7,

parts/ RA patients (RA- ↑sub-G1 cells hydroetha- FLS) nolic ext Cytotoxicity Methylferul- Aerial parts/ In vitro: Human Up to 1.5 mM ↓Cell growth & proliferation, (Abaza et al., 2016) ate from T. MeOH colorectal cancer ↑apoptosis, cell cycle arrest at S &

aucheriana cells (SW1116 & G2/M phase, cyclin-dependent kinase (Decne. ex SW837) inhibitors, Walp.) B.R. ↓ROS, DNA-binding activity of NF- Baum κB, Synergistic effect with conventional anticancers Syringic acid Aerial parts/ In vitro: Human Up to 7.5 mg/ml ↓Cell growth & proliferation, (Abaza et al., 2013) from T. MeOH colorectal cancer ↑apoptosis, cell cycle arrest at S &

aucheriana cell lines (SW1116 G2/M phase, (Decne. ex and SW837) ↓DNA-binding activity of NF-κB, Walp.) B.R. Synergistic effect with conventional Baum anticancers T. dioica Aerial parts/ In vitro: Human 100 μg/ ml Strong inhibitory effect on H. pylori- (Zaidi et al., 2012) Roxb. ex hydroetha- gastric cancer cell induced IL-8 secretion by AGS cells, Roth nolic ext line AGS infected No direct cytoprotective effect on with H. pylori AGS cells, No bactericidal effects on H. pylori T. gallica L. Aerial parts/ In vitro: Human 0.01- 100 μg/ml ↓Cell growth & proliferation, (Boulaaba et al., 2013)

hyrometha- colon cancer cells Cell cycle arrest at G2/M phase, nolic ext (Caco-2) Involvement of cyclin B1, p38, Erk1/ 2, Chk1, & Chk2 T. gallica L. Aerial parts/ In vitro: Rat brain 50-250 μg/ml ↓Cell proliferation in a dose- (Fellah et al., 2018) EtAc tumor (C6) & dependent manner human cervix carcinoma (Hela) cells T. Flower/ In vitro: Human 0.1-1000 μg/ml Induction of cytotoxicity: EtAc & (Bakr et al., 2013) senegalensis hydrometha- liver (Huh-7) & chloroform being the most potent DC. (syn: T. nolic ext lung (A-549) cytotoxic sub-extracts nilotica carcinoma cells (Ehrenb.) Bunge) T. ND/ four In vitro: Human 3.12-100 μg/ml ↓Cell proliferation, angiogenesis, w (Hassan et al., 2014) senegalensis exts breast (MCF-7) and ith aqueous ext being the most active DC. (syn: T. colon (HCT 116) one, nilotica cancer cells, Lower toxicity for normal cells (Ehrenb.) Normal CCD & compared with cancerous cells Bunge) HUVEC cells, Rat aortic ring assay Hepatoprotective T. dioica Root/ In vivo: 100, 200 mg/kg/day ↓AST, ALT (Riaz et al. 2018) Roxb. ex aqueous ext Acetaminophen- Roth induced hepatotoxicity in mice T. gallica L. Aerial parts/ In vivo: 25 & 50 mg/kg/day ↓Tumor promotion & (Sehrawat and Sultana, MeOH ext diethylnitrosa- hyperproliferation, 2006a) mine-induced & 2- ↓AST, ALT, LDH, GGT acetyl aminofluorene- induced liver carcinogenesis in rats T. gallica L. Aerial parts/ In vivo: 25 & 50 mg/kg/day ↑GSH, Gpx, SOD activity, (Sehrawat and Sultana,

MeOH ext Thioacetamide- ↓GST, XO, H2O2, LPO, AST, ALT, 2006b) induced LDH, GGT, hepatotoxicity in ↓tumor promotion rat T. gallica L. Leaf/ In vivo: 25-100 mg/100g BW/ ↓ALT, (Tabassum et al., 2006) hydroetha- Acetaminophen- day Improvement in histology of liver nolic induced hepatotoxicity in mice (continued on next page)

15 R. Bahramsoltani, et al. Journal of Ethnopharmacology 246 (2020) 112245

Table 3 (continued)

Pharmacological activity Plant species Part/ extract Model Dosage or concentration Results Reference

T. gallica L. Leaf/ ND In vivo: 100, 200 mg/kg/day ↓AST, ALT, ALP, bilirubin, LDH, TC, (Urfi et al., 2018) Rifampicin ↑Alb, total protein +isoniazid- induced hepatoxicity in rats

T. Flower/ In vivo: CCl4- 100 mg/kg/day ↓AST, ALT, ALP (Abouzid and Sleem, senegalensis hydroetha- induced 2011) DC. (syn: T. nolic ext hepatotoxicity in nilotica rats (Ehrenb.) Bunge)

T. Aerial parts/ In vivo: CCl4- 50 & 100 mg/kg/day ↓AST, ALT, LPO, hydroxyproline, (Sekkien et al., 2018) senegalensis alcohol- induced TNF-α, NF-κB, COX-2, CAT, α- DC. (syn: T. soluble hepatotoxicity in smooth muscle actin, nilotica fraction of rats ↑GSH (Ehrenb.) the aqueous Bunge) ext Toxicity T. aphylla Leaf/ MeOH In vivo: Acute 500-2100 mg/kg/day No sign of toxicity (Ullah et al., 2017) (L.) H.Karst. toxicity study in mice T. aphylla Leaf/ EtOH In vivo: Acute 50-2000 mg/kg No sign of toxicity (Yusufoglu and (L.) H.Karst. toxicity study in Alqasoumi, 2011) rats T. aphylla Leaf/ In vivo: Brine 50-500 mg/ ml Induction of 10-70% death (Muhammad et al., 2017) (L.) H.Karst. hydrometha- shrimps nolic ext

T. dioica Aerial parts/ In vivo: Brine 10- 1000 μg/ ml LC50= 500.13 μg/ ml (Keymanesh et al., 2009) Roxb. ex hydroetha- shrimps Roth nolic ext T. dioica Leaf/ In vivo: Brine 10- 1000 μg/ml Negligible cytotoxic (Khan et al., 2013) Roxb. ex different shrimps Roth fractions of the hydroethanolic ext

T. gallica L. Aerial parts/ In vitro: Larvicidal 5-11 mg/g of diet for LC50= 5 mg/g of diet for larvicidal (Soummane et al., 2011) hyrometha- & adulticidal larvicidal activity, 10-50 activity,

nolic activity against mg/ml for adulticidal LC50= 0.03-0.05 g/ml Ceratitis capitata activity

T. Flower/ In vivo: Acute ND LD50=6.4 g/kg (Abouzid and Sleem, senegalensis hydroetha- toxicity study in 2011) DC. (syn: T. nolic ext mice nilotica (Ehrenb.) Bunge) Wound healing T. aphylla Leaf/ EtOH In vivo: Excision 15%, 25% in gel base ↑Wound contraction, (Yusufoglu and (L.) H.Karst. wound model in ↓wound closure time Alqasoumi, 2011) rats T. aphylla Leaf/ In vivo: Circular ND ↑Collagen, DNA content, & total (Ali et al., 2019) (L.) H.Karst. hydroetha- excision & linear protein of the wounded tissue, nolic ext incision wound ↑wound contraction, model in rats ↑tensile strength

Abbreviations: EtOH: ethanol, MeOH: methanol, FBS: fasting blood sugar, TC: total cholesterol, HDL-C: high-density lipoprotein cholesterol, BW: body weight, GSH: reduced glutathione, AST: aspartate transaminase, ALT: alanine transaminase, ALP: alkaline phosphatase, ALX: alloxan, STZ: streptozotocin, LD50: lethal dose 50%, LC50: lethal concentration 50%, CCl4: carbon tetrachloride, ext: extract, Gpx: glutathione peroxidase, GST: glutathione-S-transferase, XO: xanthine oxidase, SOD: superoxide dismutase, LPO: lipid peroxidation, H2O2: hydrogen peroxide, LDH: lactate dehydrogenase, GGT: γ-glutamyl transpeptidase, TNF: tumor necrosis factor, COX: cyclooxygenase, NF-κB: nuclear factor-κB, CAT: catalase, Hb: hemoglobin, MWM: Morris-water maze, Alb: albumin, ROS: reactive oxygen species, Aβ: amyloid β, hIAPP: human islet amyloid polypeptide, Chk: checkpoint kinase, Erk: extracellular signal-regulated kinase, LPS: lipopolysaccharide, MIC: minimum inhibitory concentration, NO: nitric oxide, iNOS: inducible nitric oxide synthase, EtAc: ethyl acetate, ND: not determined, JNK: c-Jun N-terminal kinase, MAPK: Mitogen- activated protein kinase.

be considered that the yield of essential oil is reported to be dramati- the presence of some alcohols and aldehydes in these plants; however, cally low (0.07–0.57%) as expected since Tamarix spp. do not usually aliphatic hydrocarbons and ketones comprise the major components of possess any special aroma (Bughio et al., 2018; Saidana et al., 2008). the essential oil. Some phytosterols including avenasterol, stigmasterol, Thus, volatile terpenes cannot be considered as major participants in and cholesterol derivatives are identified in the petroleum ether extract biological activities of these plants. of T. gallica (Andhiwal et al., 1982). Also, some simple carbohydrates such as mannose, arabinose, and sucrose were isolated from the ethyl acetate extract of the gum or gall of tamarisk (Table 2). 4.3. Miscellaneous phytochemicals

Analysis of essential oil isolated form some Tamarix species showed

16 R. Bahramsoltani, et al. Journal of Ethnopharmacology 246 (2020) 112245

Table 4 Quality assessment of animal studies on the pharmacological activity of Tamarix spp. according to Animal Research: Reporting of In Vivo Experiments (ARRIVE) guideline

Reference Validity Ethical Animals Experimental Housing & Numbers Interpretation & scientific Generalizability statement procedures husbandry analyzed implications /translation

(Abouzid and Sleem, - + + + + + - - 2011) (Ali et al., 2019) - + + - + + - - (Chaturvedi et al., 2012) - + + + + + - - (Habiba et al., 2010) - + + + + + - - (Hebi and Eddoucks, - + + + + + - + 2017a) (Hebi et al., 2017b) - + + - + + - - (Hebi et al., 2018) - + - + - - - - (Qadir et al., 2014) - + + + + + - + (Rahman et al., 2011) - + + + + + - - (Riaz et al., 2018) - + + + + - - + (Salissou et al., 2018)-- + - + + - + (Sehrawat and Sultana, - + + + + + - - 2006a) (Sehrawat and Sultana, -- + + + + - - 2006b) (Sekkien et al., 2018) - + + - + + - - (Tabassum et al., 2006)-- + - - + - - (Ullah et al., 2017) - + + + + + - + (Urfi et al., 2018) - + + + + + - + (Yusufoglu and - + + + + + - + Alqasoumi, 2011)

Fig. 1. Structure of the most important phytochemicals of Tamarix spp. a: quercetin, b: tamarixetin, c: kaempferol, d: isorhamnetin, e: ellagic acid, f: syringic acid, g: gallic acid.

5. Pharmacological activities Mahfoudhi et al. (2016) have assessed the anti-cholinesterase activity of T. aphylla extract. Amongst extracts obtained with solvents 5.1. Anti-alzheimer effect with different polarities, ethyl acetate extract showed the highest potency with 21% and 16.7% inhibition of acetylcholinesterase by the leaf Alzheimer's disease (AD) is known as the most common neurode- and stem extract, respectively; however, none of the extracts could generative disorder which is accompanied with cognitive decline and inhibit butyrylcholinesterase. This can be attributed to the presence of memory loss. At cellular level, the presence of β-amyloid plaques and phenolic acids (p-coumaric acid in the ethyl acetate extract and gallic abnormal Tau proteins are the hallmarks of AD. Current available acid and ellagic acid in polar extracts) which have previously demon- medicines for AD include acetylcholine esterase inhibitors such as do- strated acetylcholinesterase inhibitory activity (Mahfoudhi et al., nepezil, and N-methyl-d-aspartate (NMDA) receptor antagonist like 2016). Another study assessed the effect of ten flavonoids from T. gallica memantine (Cummings et al., 2015); however, they mostly act as a on the β-amyloid (Aβ) aggregation (Ben Hmidene et al., 2017a). Aβ is a symptom-therapy rather than a real treatment for AD. protein with a usual 40 to 42 amino acids length which is produced

17 R. Bahramsoltani, et al. Journal of Ethnopharmacology 246 (2020) 112245 during the routine brain metabolism; however, its abnormal accumu- with glucose intolerance and insulin resistance which is increasingly lation in brain can form Aβ plaques which are one of the important growing all over the world. Current available antihyperglycemic drugs hallmarks of AD (Panza et al., 2019). The highest in vitro inhibitory act via various mechanisms mainly include regulation of glucose ab- activity on Aβ1-42 aggregation was observed with quercetin 3-O-β-D- sorption, insulin secretion and insulin sensitivity (Rezaeiamiri et al., glucuronide, followed by naringenin with IC50 values 3.8 and 9.3 μM, 2019). There are some in vitro and in vivo evidence suggesting Tamarix respectively. Since catechol-bearing structures had a lower IC50, au- spp. to be able to manage DM. T. aphylla and T. gallica extracts have thors have suggested that catechol ring plays an important role in demonstrated inhibitory effect on α-glucosidase activity, a series of molecular interactions leading to the inhibition of Aβ aggregation. important enzymes in carbohydrate absorption from gastrointestinal Additionally, the presence of glucuronide can increase the inhibitory tract, which is a mechanism similar to acarbose drug (Ben Hmidene activity of the flavonoids on Aβ aggregation; whereas O-methylation et al., 2017a; Mahfoudhi et al., 2016). Further analyses of the in- decreases this effect (Ben Hmidene et al., 2017b). Intragastric admin- dividual compounds of T. gallica extract showed that five compounds istration of hydromethanolic extract of T. gallica also represented in vivo including quercetin, rhamnetin, rhamnazin, tamarixetin, and kaemp- anti-AD effect in homocysteine-induced AD in rats with the dose of100 ferol have mixed inhibition on sucrase and maltase enzymes; whereas and 300 mg/kg which was evident from reduction of spatial memory their O-methylated and glucuronosylated derivatives represented non- impairment in Morris-water maze. Molecular assessments showed up- competitive inhibition of these enzymes. All compounds showed a dose- regulation of the synaptic proteins and reduction of inflammation dependent inhibitory activity (Ben Hmidene et al., 2017a). T. aphylla biomarkers such as interleukin-1β (IL-1β) and tumor necrosis factor-α had IC50 values significantly lower than that of acarbose which meansa (TNF-α) which consequently decreased neurodegeneration. Aβ accu- higher potency (Mahfoudhi et al., 2016). Assessment of O-methylated mulation and Tau protein hyperphosphorylation which are two main and glucuronosylated flavonoids of T. gallica showed that catechol ring contributors of AD pathogenesis were also decreased by T. gallica ex- and glucuronic acid are important functional groups for α-glucosidase tract with a significantly better effect by the higher dose(Salissou et al., inhibitory activity. Simultanous administration of the most potent fla- 2018). It should be mentioned that only two doses were used in this vonoids with acarbose showed a synergistic effect which may suggest study; whereas use of more than two doses can provide a better clar- these flavonoids to reduce the total recommended dose and subse- ification of the dose-resonse relationship which can be considered in quently, side effects of acarbose; however, this hypothesis need tobe future studies. In addition to the above-mentioned mechanisms which further confirmed in human studies (Ben Hmidene et al., 2017b). In the are directly associated with AD, there are some evidence suggesting rat model of streptozotocin (STZ)+nicotinamide-induced DM which tamarisk to have anti-inflammatory properties against microglia in- mimics type 2 DM, methanolic extract of T. aphylla revealed anti- flammation. It is demonstrated that microglia inflammation partici- hyperglycemic effect at the doses 100–400 mg/kg, evident fromthe pates in the development of neurodegenerative diseases, including AD reduction in both fasting blood sugar (FBS) and glycosylated he- (Cameron and Landreth, 2010). T. smyrnensis Bunge (Syn: T. hohe- moglobin (HbA1c) in a dose-dependent manner which was relatively nackeri Bunge) reduced inflammation biomarkers such as ILs, TNF-α, the same as glibenclamide with the highest dose (Ullah et al., 2017). and inducible nitric oxide synthase (iNOS) in lipopolysaccharide-in- Hebi et al. (2017) also reported antihyperglycemic effect of T. aphylla duced inflammation in BV-2 microglia cells in a dose-dependent (syn: T. articulata) which was more potent than the former study since it manner. This effect seems to be mediated via nuclear factor-κB (NF-κB) could be effective at a dose of 5 mg/kg similar to 5 mg/kg ofglib- which is an important cellular signaling involved in inflammation. Also, enclamide. This higher activity might be due to the difference between 13 purified compounds were individually assessd at a concentration phytochemicals of the extracts used in the two studies since the former range between 0.1 and 100 μM; though, some of these purified phyto- has used methanolic extract; whereas the latter was an aqueous extract chemicals represented cytotoxicity at higher concentrations which de- which provides a different profile of phytochemicals. Additionally, the finitely affects their effect on LPS-induced damages. Phytochemical species and harvest area of the plants were different between the two analysis showed that four compounds, including two phenolic acids and studies which definitely play a role in the antihyperglycemic activity of two flavonoids, are the active ingredients of the extract, with quercetin the extracts. Another study also confirmed the anihyperglycemic and being the most important one (Chen et al., 2018). Although quercetin antihyperlipidemic properties of a flavonoid-rich extract from T. ar- and its derivatives are widely found in different edible plants, it has ticulata with both single and multiple dose administration to diabetic been demonstrated that the food matrix is an important determining rats at the dose of 5 mg/kg which shows the pharmacological activity of factor in the pharmacokinetics/pharmacodynamics of this phytochem- the plant, at least in part, is due to the presence of flavonoids in the ical; thus, it is not farfetched that quercetin in the matrix of tamarisk extract (Hebi et al., 2018). Since only one dose of the extract was ad- extract exert specific pharmacological activities (Hollman et al., 1997). ministered to the animals in the two latter studies, further evaluations It should be considered that in cellular assements, the cells are directly are needed to provide a dose-reponse curve and obtain the most efec- exposed to the extract/phytochemicals; whereas in a living organism, tive antihyperglycemic dose of the extract. Although STZ- and the extract would be definitely affected by several factors such asgas- STZ + nicotinamide-induced DM are considered as the animal models trointestinal enzymes and hepatic first-pass metabolism and thus, the of type 2 DM, high-fat high-carbohydrate-induced obesity and DM may concentration of each coumpound of the extract which reaches the cells be a better predictor of the efficacy in humans since type 2 DM is deeply should be analysed with pharmacokinetic evaluations in animal models involved with bad eating habits (Asrafuzzaman et al., 2017). The ex- or human studies. Also, the memory enhancing effects of Tamarix spp. tract could also be effective on the reduction of DM-related hyperlipi- should be further investigated in behavioral animal models since an- demia via decrease in total cholesterol and triacylglycerol, as well as imal responses in behavioral models like Morris water maze are very elevation of high-density lipoprotein cholesterol (Hebi and Eddouks, susceptible to environmental factors such as the operator and use of 2017a). Antidiabetic activity of Tamarix spp. can be attributed to the suitable positive and negative control groups is important to exclude phenolic compounds such as quercetin and ferulic acid which have the risk of bias. Studies assessing a series of concentrations of the test previously demonstrated protective effects on pancreatic beta cells material are needed to provide a dose-respone relationship and define (Coskun et al., 2005; Ramar et al., 2012). Antioxidant properties of the effective concentration range for human studies. these phytochemicals may be an important mechanism since previous literature have shown the importance of oxidative damage in the pa- 5.2. Effects on metabolic parameters thogenesis of DM (Rahimi et al., 2005).

One of the traditional uses of tamarisk is for the treatment of diabetes mellitus (DM). Type 2 DM is a metabolic disorder characterized

18 R. Bahramsoltani, et al. Journal of Ethnopharmacology 246 (2020) 112245

5.3. Anti-inflammatory and antinociceptive effects of Gram positive and Gram negative bacteria including Escherichia coli (Migula, 1895) Castellani and Chalmers, 1919 and Staphylococcus Inflammation is a common stage in the pathogenesis of several aureus Rosenbach, 1884; however, its effectiveness did not achieve to diseases (Hunter, 2012). Polyphenols are one of the main categories of the control drugs (Bughio et al., 2018; Saidana et al., 2008). Also, re- phytochemicals with anti-inflammatory properties; thus, Tamarix spp. markably low yield of essential oil extraction in these studies which mainly contain polyphenols as their secondary metabolites can (0.07–0.57%) suggest these herbal preparations not to be a good can- show promising anti-inflammatory properties (Rasouli et al., 2017). T. didate for further evaluations. Benmerache et al. (2017) could isolate aphylla extract has been evaluated regarding its anti-inflammatory ef- purified flavonoids from T. amplexicaulis Ehrenb. (syn: T. balansae fects in rat paw edema induced by sub-plantar injection of carrageenan. J.Gay) with good antibacterial activity. It was observed that presence of In oral administration of the extract, no significant anti-inflammatory potassium sulfate in kaempferol derivatives and rhamnopyranose in effect was observed; however, it could successfully increase pain quercetin derivatives increases the antibacterial activity (Benmerache threshold in acetic acid-induced writhing, hot plate test, and formalin- et al., 2017). Several other Tamarix species from different parts of the induced paw licking in mice, with a potency near to 100 mg/kg of world are assessed regarding their antimicrobial properties against Aspirin as the gold standard, suggesting the analgesic effects of the major human pathogenic bacteria and fungi (Table 3). Overall, it seems extract to be independent of the anti-inflammatory properties (Qadir that the antifungal activity of Tamarix spp. is stronger than its anti- et al., 2014). In another study, topical application of a gel containing bacterial properties since studies demonstrated higher activity against the plant extract could significantly reduce paw edema at 15% and25% Aspergillus spp. and Candida spp. (Awaad et al., 2014; Khan et al., 2013; concentrations in a dose-dependent manner. While the positive control Mandeel and Taha, 2005; Muhammad et al., 2017). Though, in case of drug (topical diclofenac) showed 80.7% inhibition, 15% and 25% T. gallica, the antifungal activity is not that strong and antibacterial herbal gel had 20.61% and 53.07% inhibitory activity on paw edema, properties, especially regarding the compounds extracted from n-bu- respectively (Yusufoglu and Alqasoumi, 2011). Considering that the tanol fraction, seem to be more promising (Ksouri et al., 2009; Lefahal concentration of diclofenac in the topical gel (1%) is much lower than et al., 2010). It can be concluded that the antibacterial properties of the herbal preparations, the tamarisk extract in this form is not a potent Tamarix spp. dramatically depends on the species and cultivation area, topical anti-inflammatory treatment and should be further concentrated as well as the method/solvent used for the extraction of active com- or fractionated for the purification of the active compounds and in- pounds. It is worthy to mention that most of the studies regarding an- crease the anti-inflammatory potency. T. gallica extract at 100–300 mg/ timicrobial activities of Tamarix spp. are in vitro evaluations which does kg could significantly reduce carrageenan- and histamine-induced hind not guarantee the same in vivo effects. Also, some studies did not con- paw edema in rats in a dose-dependent manner which suggest the anti- sider an antibiotic as a positive control; thus, the reported inhibition inflammatory of the extract to be mediated via antihistamine proper- zones or MICs cannot be compared with any standard drug. Even in ties. The extract was also effective in tail flick test which is ananimal those used a positive control, the inhibitory activity of the extracts model for central pain, as well as hot plate and acetic acid-induced against the microbial growth does not reach the potency of the gold writhing in mice; though, in all tests, the gold standard drugs (10 mg/kg standard so that the extract cannot be simply recommended as a re- of diclofenac and 100 mg/kg of Aspirin) were stronger than the herbal placement for conventional antimicrobial agents. In vivo models such as treatments (Chaturvedi et al., 2012). Anti-inflammatory properties in wounds infected with the specific microorganisms, as well as evaluation carrageenan model is also reported for the root extract of T. indica of antimicrobial activity against clinically-isolated strains can provide Willd. from Bangladesh at 200 and 400 mg/kg, along with an anti- more reliable results which should be considered for future studies. nociceptive activity in acetic acid-induced writhing at 250 and 500 mg/ kg (Rahman et al., 2011). Methanolic extract of T. indica leaf also 5.5. Antineoplastic properties showed the same antinociceptive potency with inhibition of acetic acid- induced writhing at 500 mg/kg in mice (Habiba et al., 2010). Anti-in- Tamarix species have been assessed in different cancerous cell lines. flammatory effects of Tamarix species is possibly due to the presence of In human colorectal Caco-2 cells, hydromethanolic extract of T. gallica flavonoids such as quercetin derivatives (Kim et al., 2004), as well as reduced cell growth and proliferation via modulation of proteins in- phenolic acids like gallic acid (Kahkeshani et al., 2019) and p-coumaric volved in cell cycle such as cyclin B1 and p38 which resulted in cell acid (Pragasam et al., 2013) which is demonstrated in several previous cycle arrest at G2/M phase and the potency was nearly the same be- literatures; though, detailed underlying mechanisms still need to be tween shoot, leaf, and flower extracts (Boulaaba et al., 2013). T. gallica investigated in further studies. Since the effective dose in most of the has also demonstrated antiproliferative properties in rat brain tumor studies is much higher than that of diclofenac (10 mg/kg), crude ex- (C6) and human cervix carcinoma (Hela) cells. Results of the study by tracts of Tamarix spp. seem to have moderate to low anti-inflammatory Fellah et al. (2018) showed that T. gallica grown in arid and humid effects. Additionally, none of the studies reviewed in this section have climates have higher phenolic content and represented more potent performed a quantitative phytochemical analysis; thus, the negative or antiproliferative activity compared with plant materials from semi-arid positive results of these studies cannot be strongly attributed to any climate which shows the effect of climate on phytochemical profile and phytochemical/phytochemical category which shows the neccessity of biological activities. Tamarisk extracts from arid and humid climates accurate phytochemical analyses to better discuss the active ingredients showed higher antiproliferative activity compared with the standard of the extracts. drug 5-flourouracil (5-FU) at the same concentrations (Fellah et al., 2018). Another tamarisk species, T. senegalensis (syn: T. nilotica), re- 5.4. Antimicrobial properties presented antineoplastic properties in human liver (Huh-7) and lung (A- 549) carcinoma cells with different extracts and the highest activity was Antimicrobial activity of Tamarix spp. has been evaluated against a observed with the ethyl acetate sub-extract followed by the chloroform series of bacterial and fungal species. Tamarix senegalensis DC. (syn: T. sub-extract, suggesting the presence of higher content of active bio- nilotica (Ehrenb.) Bunge) and T. aphylla showed antibacterial activity molecules which was also correlated with higher in vitro radical against Porphyromonas gingivalis (Coykendall et al., 1980) Shah and scavenging activity (Bakr et al., 2013). T. senegalensis (syn: T. nilotica) Collins, 1988 and biofilm-forming bacteria, respectively, which are extract also showed inhibitory effect on angiogenesis in the rat aortic important oral cavity pathogens involved in periodontitis and gingi- ring test which shows its ability to prevent the invasion and metastasis vitis, confirming the traditional use of the plant in dental infections of cancer cells. The plant extract decreased the growth and proliferation (Khalid et al., 2017; Mohieldin et al., 2017). Essential oils from T. bo- of human breast (MCF-7) and colon (HCT 116) cancer cells, with aqu- veana and T. dioica demonstrated antibacterial activity against a series eous extract being the most potent one. It is worthy to mention that the

19 R. Bahramsoltani, et al. Journal of Ethnopharmacology 246 (2020) 112245 cytotoxicity of the extract was significantly lower in normal cells that dose could only improve alkaline phosphatase (ALP), lactate dehy- shows the specificity of its cytotoxic effects for cancerous cells(Hassan drogenase (LDH), and albumin (p < 0.05). Also, the extract decreased et al., 2014). Zaidi et al. (2012) evaluated the effect of T. dioica extract systemic inflammation, evident from the reduction of LDH(Urfi et al., in AGS (human gastric cancer) cells infected with Helicobacter pylori 2018). Thioacetamide, a fungicide, is another agent which induces both (Marshall et al., 1985) Goodwin et al., 1989, a bacterium which makes hepatocellular damage and carcinogenesis. T. gallica extract at the doses gastric cells susceptible to be turned into cancerous cells. The extract of 25 and 50 mg/kg significantly reversed the elevated hepatic enzymes could significantly reduce IL-8 secretion induced by H. pylori; however, via improvement of endogenous antioxidant defense mechanisms such this effect was independent of the direct antiproliferative oranti- as GSH and superoxide dismutase activity (Sehrawat and Sultana, bacterial activity of the extract. Since IL-8 is an important mediator in 2006b). Additionally, the extract modulated hepatic xanthine oxidase the inflammatory response of gastric cells to H. pylori infection, this and glutathione S-transferase which play a role in the detoxification of finding recommends tamarisk to be a possible chemopreventive agent xenobiotics. T. gallica extract also demonstrated antihepatocarcinogenic in prevention of H. pylori-induced malignancies (Zaidi et al., 2012). effect via prevention of tumor promotion in the animals; though, dueto Methylferulate and syringic acid isolated from methanolic extract of the lack of a positive control group, the potency of the extract cannot be T. aucheriana (Decne. ex Walp.) B.R. Baum demonstrated antineoplastic discussed (Sehrawat and Sultana, 2006a). Another Tamarix species, T. activity in SW1116 and SW837 human colorectal cancer cell lines. Both senegalensis (syn: T. nilotica) have exhibited hepatoprotective properties phytochemicals induced apoptosis via cell cycle arrest at S & G2/M in carbon tetrachloride-induced liver damage at 50 and 100 mg/kg phase and decrease in DNA binding activity of NF-κB(Abaza et al., which is attributed to its antioxidant properties via elevation of GSH 2013, 2016). Additionally, methylferulate could regulate the cyclin- (Abouzid and Sleem, 2011; Sekkien et al., 2018). The extract could dependent kinase inhibitors (Abaza et al., 2016) which are today con- reduce liver fibrosis, evident from the decreased hydroxyproline considered as new targets for anticancer therapies (Law et al., 2015). tent and α-smooth muscle actin. This effect was mediated through anti- In vitro studies on the antineoplastic activities of plant extracts are inflammatory activity of the plant via reduction of TNF-α, NF-κB, and mainly valuable due to the possibility of assessing underlying me- cyclooxygenase (COX) 2 enzyme, an enzyme responsible for the pro- chanisms and only evaluating the effect on cell viability, the same as duction of pro-inflammatory mediators such as prostaglandins. The some of the reports included in our review (Table 3), is not a valuable plant also exerted antioxidant properties which decreased lipid perox- report since cell cultures are much susceptible to environmental factors idation and improved endogenous antioxidants, including GSH and such as temperature and osmotic pressure and the lower viability rate catalase (Sekkien et al., 2018). It should be noted that in all parameters, may be due to a reason other than the plant extract. Another reason for the higher dose of the extract showed a better efficacy which was si- low reliability of in vitro antineoplastic studies is that in a living or- milar to the positive control (silymarin) in most parameters. ganism, several other cells except than the target tissue are exposed to the plant extract; thus, the extract may be toxic for normal tissues as 5.7. Miscellaneous pharmacological activities well, which is one of the main reasons for several agents being pre- vented to be clinically used as an anticancer. Another problem is that Tamarix species are rich in flavonoids and tannins with astringent cancerous cells usually develop resistance in long-term exposure to properties; thus, it is not farfetched to have wound healing properties. anticancer agents which is one of the major reasons why researchers Ethanolic extract of T. aphylla leaves as a topical gel has been assessed always seek new anticancer agents. So, an in vitro antineoplastic activity in a rat model of excision wound which could increase wound healing is not equal to anticancer effect and higher level of evidence suchas rate; however, the results were compared to Betadine as positive con- antitumor properties in tumor-bearing animals should be provided to trol which is an antiseptic agent and has a different mechanism of ac- clarify whether or not a plant is worthy to be further investigated as a tion from a wound healer. Comparison of the results with a standard source of anticancer agents. wound healing agent such as gotu kola (Centella asiatica (L.) Urb.) preparations may give a better comparison regarding the wound 5.6. Hepatoprotective effects healing activity of T. aphylla (Yusufoglu and Alqasoumi, 2011). This effect is demonstrated in another study with the same model, aswell Hepatotoxicity is one of the side effects of several medicines and linear incision wound. The extract showed better tissue repair com- toxicants which is usually accompanied with oxidative stress, in- pared with the control group which was evident from increased protein flammation, and mitochondrial damage (Jaeschke et al., 2012). In content of the damaged area, as well as the improved tensile strength; acetaminophen-induced hepatotoxicity in mice which results in over- though, lack of a positive control group makes the result to be less production of N-acetyl-p-benzoquinone imine and hepatic glutathione reliable (Ali et al., 2019). Astringent properties of tamarisk are also (GSH) depletion, 100 and 200 mg/kg of T. dioica root extract could useful for the treatment of diarrhea which is also mentioned in tradi- significantly reduce abnormally increased levels of the hepatic en- tional and local uses of the plant and is demonstrated in the animal zymes, aspartate transaminase (AST) and alanine transaminase (ALT), model of castor oil-induced diarrhea in mice (Habiba et al., 2010). This in comparison to the negative control; however, there was no sig- effect may be useful for the treatment of non-infective diarrhea sinceno nificant difference between the high and low doses of the extract. Also, antibacterial effects against enteric pathogens are reported inthis no positive control group was considered in this study and the results study. Also, the potency of 500 mg/kg of the extract was lower than cannot be compared with a standard hepatoprotective agent (Riaz et al., 25 mg/kg of loperamide and thus, a high amount of the extract should 2018). T. gallica leaf extract also demonstrated hepatoprotective ac- be taken to achieve the required therapeutic effect. tivity in the same animal model at 250–1000 mg/kg. Although no po- In vitro assessment of antiplatelet activity of T. smyrnensis (Syn: T. sitive control group was used, histopathological examinations showed a hohenackeri) from China showed that the ethyl acetate fraction is the higher tissue regeneration which supports the hepatoprotective effects most active extract. Further isolation and identification of the phyto- of the plant (Tabassum et al., 2006). In the rat model of hepatotoxicity chemicals showed that chrysoeriol and dillenetin, two flavonoid induced by rifampicin and isoniazid, two main antituberculosis medi- structures, have the highest antiplatelet activity. Also, chrysoeriol and cines with concerning hepatotoxicity, T. gallica extract could recover quercetin, as well as some phenolic acid derivatives showed potent hepatic enzymes at the dose of 100 and 200 mg/kg. The higher dose inhibitory effect on angiotensin converting enzyme which suggests the showed similar efficacy to 100 mg/kg of silymarin (positive control), plant to be potentially applicable in cardiovascular problems (Xing except in case of albumin, total protein, and serum bilirubin which was et al., 2014). T. gallica hydromethanolic extract is also evaluated re- less potent than silymarin, but still showed significantly (p < 0.05) garding its antithrombin properties; however, the extract showed no better results than those of the negative control. However, the lower inhibitory activity against thrombin. On the other hand, it was a potent

20 R. Bahramsoltani, et al. Journal of Ethnopharmacology 246 (2020) 112245 inhibitor of trypsin enzyme, possibly due to the presence of tannins, effects are still questionable according to the studies included inthis which may be a candidate for gastrointestinal complications due to review due to the methological problems. Some methods used in animal hypersecretion of trypsin (Jedinak et al., 2010). studies like some of the included studies on the hepatoprotective effects Tamaractam, isolated from T. ramosissima, decreased survival of of Tamarix spp. are poorly reported and do not have an appropriate human fibroblast-like synoviocytes which is an in vitro model of rheu- design due to the lack of a positive control group which makes the matoid arthritis. This compound induced apoptosis via activation of results less reliable. Also, some pharmacological studies like those as- caspase 3 and 7 and increased sub-G1 cells which suggest it as an anti- sessed the anti-inflammatory and antinociceptive properties only used a rheumatoid agent (Yao et al., 2017). simple animal model without further investigating the undelying mechanisms of action such as the involved receptors or inter- and in- 6. Safety concerns tracellular pathways. Since most of the diseases have complicated mechanisms involved in their pathologies, it is important to clarify which Toxicity studies performed on different Tamarix species have pro- of the malfunctions is reversed by the herbal treatment so that the vided controversial results. In brine shrimp lethality test, a primary possible herb-drug interactions can be predicted in case of human use method for detection of toxicity of a new compound, T. aphylla and T. (Bahramsoltani et al., 2017). Another problem is that some of the an- dioica from Saudi Arabia and Pakistan showed negligible toxicity (Khan imal studies on Tamarix spp. have assessed only two doses/concentra- et al., 2013; Yusufoglu and Alqasoumi, 2011); however, two other tions of the extract which do not provide a reliable dose-response re- studies reported toxicities for these two species in the same model lationship. For instance, in the study by Salissou et al. (2018), 100 and (Keymanesh et al., 2009; Muhammad et al., 2017). In acute toxicity 300 mg/kg of the extract was administered, resulting in a better effect studies in rodents, no sign of toxicity has been observed in any of the by the higher dose; however, such result cannot predict the effect of studies on different Tamarix species up to high doses (Table 3). Ta- doses lower than 100 mg/kg and higher than 300 mg/kg since it may marisk is locally used by people in several countries of Asia and Africa have an invert U-shaped dose-response curve. Thus, future studies (Table 1) and is generally considered as an edible plant (Ksouri et al., should use more than two concentrations so that a more reliable dose- 2009); thus, the reported toxicities in brine shrimp may be due to other response curve can be achieved. factors such as the solvent used for extraction (Wu, 2014). Also, the Lack of phytochemical analysis of the assessed extract is a big gap in harvest area may be an important contributor in the pharmacological the current pharmacological studies which makes the main active in- and toxicological properties of this plant since environmental factors gredients to be unknown. As discussed in the study of Fellah et al. can affect the quality and quantity of its phytochemicals. (2018), even a specific species of the plant shows different potencies in biological assessements which is due to the different phytochemical 7. Conclusion profiles occurred in various climates; thus, phytochemical analyses are essential to determine which compounds are major active ingredients of Tamarisk is an edible halophyte which is easily grown is a wide the extract (Fellah et al., 2018). Another reason for low reproducibility variety of climates, including arid areas. It is traditionally used by local of the reported pharmacological effects is the lack of a reliable plant people of Asian and African countries for the treatment of several ail- identification process. The identification of the specific species hasnot ments. Several pharmacological activities have been demonstrated for been described in some of the included studies and no voucher number Tamarix spp.; however, few commercial supplements have used this is reported, so that the taxonomic validity of the voucher speciemen plant in their formulations. One of the reason for the limited use of cannot be confirmed. Tamarix spp. is the lack of clinical studies on the therapeutic and tox- Aditionally, a large number of the studies described in Table 3 are in icological properties of these species. Our literature review failed to vitro evaluations which do not provide acceptable evidence for clinical find any human study on tamarisk. There are some studies on Liv-52,a use of the plant since a long path lies ahead from bench to bedside. For commercial product used for the management of liver disorders which instance, there are millions of plant extract and phytochemicals with in contains eight ingredients, including 16 mg/tablet of T. gallica extract vitro antineoplastic activities; though, only a few could find their way (De Silva et al., 2003; Fallah Huseini et al., 2005); though, since this into clinics. The same problem exists for in vitro antimicrobial asses- product is a polyherbal preparation, the therapeutic effect is the result sements since pathogenic microorganisims have several tricks to cir- of all included ingredient, not any of the individual plants. Another cumvent the antimicrobial agents and develop resistance in vivo. Also, problem regarding the use of tamarisk in human is the controversial we did not include the studies which only assessed the in vitro anti- results of pre-clinical toxicity studies. As discussed in the previous oxidant activity of the extracts with methods such as 2,2-diphenyl-1- section, some studies suggest toxicity for tamarisk; whereas some other picrylhydrazyl (DPPH) radical scavenging test sine in vitro antioxidant revealed no sign of toxicity in animals, even for a specific species of properties do not necessarily guarantee the same effect in a living or- tamarisk. This shows that except than the species, other factors such as ganism. the geographical region in which the plant is harvested, as well as the It is worthy to mention that the evaluated animal dose in some environmental pollutants have a crucial role in the composition and studies seem to turn into a very high equal human dose which may consequently, pharmacological activities of tamarisk. It should be re- result in a poor patient compliance. As an example, considering the minded that Tamarix spp. possess salt-excreting glands which secrete formula for dose translation from animal to human effective dose the excessive minerals absorbed form the soil; thus, presence of soil (Reagan-Shaw et al., 2008), 500–1000 mg/kg animal dose would be pollutants such as heavy metals can affect the quality of the extract equal to around 5.7–11.4 g of the extract for a 70 kg human which is obtained from the plant and may be one of the possible explanations for relatively high and would be turned into a high number of capsules/ toxicities observed in some studies. Considering that Liv-52 is a com- tablets per day. On the other hand, due to the bitter taste of the extract mercial product which has been produced and consumed for several of tamarisk, an oral syrup is not a suitable dosage form; thus, it is better years, we can conclude that optimum cultivation conditions can result to identify the active fraction of the extract to achieve a higher potency in obtaining tamarisk with acceptable safety profile for clinical use. and lower daily dose and consequently, better patient compliance. Future studies on the possible toxicity of Tamarix spp. in human is es- Moreover, dose variation in different studies on the same animal model sential to pave the way for clinical trials on the therapeutic activities of makes the decision on the effective dose range of the extract difficult. this plant genus. In this regard, dose-escalating human studies can be As an example, studies on the antidiabetic activity of the plant have helpful to define the safe and effective dose range of the plant extract. reported a dose ranged from 5 mg/kg (Hebi et al., 2017) to 400 mg/kg As previously discussed, some of the pharmacological properties of (Ullah et al., 2017). Even considering the difference in the cultivation Tamarix spp. such as anticancer, antimicrobial, and anti-inflammatory area, species, and extraction solvent, such a wide dose range is still

21 R. Bahramsoltani, et al. Journal of Ethnopharmacology 246 (2020) 112245 questionable which further suggests the need for more accurate studies. 223. In spite of all pharmacological studies reviewed in this paper, there Abouzid, S., Sleem, A., 2011. Hepatoprotective and antioxidant activities of Tamarix nilotica flowers. Pharm. Biol. 49, 392–395. are several therapeutic properties according to traditional medicine Abouzid, S.F., Ali, S.A., Choudhary, M.I., 2009. A new ferulic acid ester and other con- which have not yet been scientifically assessed. Liver and spleen are stituents from Tamarix nilotica leaves. Chem. Pharm. Bull. 57, 740–742. two main target organs of Tamarix spp. based on the traditional med- Ahmad, M., Zafar, M., Sultana, S., 2009. Salvadora persica, Tamarix aphylla and Zizyphus mauritiana-Three woody plant species mentioned in Holy Quran and Ahadith and icine and ethnopharmaclogical studies; thus, preclinical evaluations on their ethnobotanical uses in north western part (DI Khan) of Pakistan. Pak. J. Nutr. 8, the effect of Tamarix spp. on liver and spleen disorders are re- 542–547. commended. Wound healing is another properties of tamarisk which is Ahmed, A.F., Memon, M.U., Yoshida, T., Okuda, T., 1994. Tannins of tamaricaceous not yet widely studies; whereas these species can be suitable wound plants. VI.1) four new trimeric hydrolyzable tannins from reaumuria hirtella and tamarix pakistanica. Chem. Pharm. Bull. 42, 254–264. healing agents due to the high content of flavonoids and tannins with Al-Fatimi, M., 2019. Ethnobotanical survey of medicinal plants in central abyan gover- antioxidant, anti-inflammatory, and astringent effects. The phyto- norate, Yemen. J. Ethnopharmacol. 241, 111973. https://doi.org/10.1016/j.jep. chemical profile of Tamarix spp. also suggests these plants to be helpful 2019.111973. Ali, S., Alam, S., Ahmad, S., Ali, M., Ahsan, W., Siddiqui, M.R., 2019. Wound healing in gingivitis and periodontitis, as mentioned in traditional medicine. activity of alcoholic extract of tamarix aphylla L. On animal models. Biomed. Thus, wound healing and periodontology apllications seem to be ap- Pharmacother. J. 12, 41–48. propriate priorities to be assessed in clinical studies. On the other hand, Alnuqaydan, A.M., Rah, B., 2019. Tamarix articulata (T. Articulata) - an important ha- lophytic medicinal plant with potential pharmacological properties. Curr. despite the use of tamarisk for some infectious diseases such as tu- Pharmaceut. Biotechnol. 20 (4), 285–292. berculosis, leprosy, and smallpox in traditional medicine, modern an- Alzweiri, M., Sarhan, A.A., Mansi, K., Hudaib, M., Aburjai, T., 2011. timicrobial assessments do not suggest these plants as potent anti- Ethnopharmacological survey of medicinal herbs in Jordan, the Northern Badia region. J. Ethnopharmacol. 137, 27–35. microbial agents since the extracts were inactive against several Andhiwal, C.K., Kishore, K., Itoh, T., Matsumoto, T., 1982. Unusually high ratio of sa- bacterial and fungal species and even in those inducing an inhibitory turated/unsaturated sterols in Tamarix gallica. J. Nat. Prod. 45, 222–223. effect, the potency was not comparable with standard antibiotics. Also, Aslam, M.S., Roy, S.D., Ghaffari, M.A., Choudhary, B.A., Uzair, M., Ijaz, A.S., Khan, T.R., 2014. Survey of ethno-medicinal weeds of district Rajhan pur, Punjab, Pakistan. there are several species of Tamarix which have not yet been analysed Indian. Res. J. Pharm. Sci. 1 (2), 38–45. regarding their phytochemicals and pharmacological properties which Asrafuzzaman, M., Cao, Y., Afroz, R., Kamato, D., Gray, S., Little, P.J., 2017. Animal provides a wide area of research on the plants of this genus. In arid models for assessing the impact of natural products on the aetiology and metabolic climates, Tamarix spp. are cultivated for fixing sands which needs fi- pathophysiology of Type 2 diabetes. Biomed. Pharmacother. 89, 1242–1251. Avicenna, 1991. The canon of medicine (Qanoon-fil-Tib). Translated by sharafkandi. A. nancial investments. Defining therapeutic activities for tamarisk and Tehran: Soroush 2, 167–168. preparation of products based on this plant can return part of the Awaad, A.S., Zain, M.E., Al Othman, M.R., Al-Dosary, S.K., 2014. Phytochemical analysis budget used for the cultivation of tamarisk and thus, can provide an and antimicrobial activity of medicinal plants against pathogenic microorganisms. Life Sci. J. 11, 350–354. economic added value to this plant. Aykac, A., Akgul, Y., 2010. A new analogue of fatty alcohol from Tamarix hampeana L. In conclusion, Tamarix species are valuable plants rich in several Nat. Prod. Res. 24, 34–39. phytochemicals including polyphenols and have numerous number of Baaka, N., Mahfoudhi, A., Haddar, W., Mhenni, M.F., Mighri, Z., 2017. Green dyeing process of modified cotton fibres using natural dyes extracted from Tamarix aphylla pharmacological and therapeutic properties based on both traditional (L.) Karst. leaves. Nat. Prod. Res. 31, 22–31. medicine and scientific experiments. There is currently a big gapre- Bahadur, S., Khan, M.S., Shah, M., Shuaib, M., Ahmad, M., Zafar, M., Begum, N., Gul, S., garding the clinical data supporting the therapeutic activities of Ashfaq, S., Mujahid, I., 2018. Traditional usage of medicinal plants among the local communities of Peshawar valley, Pakistan. Acta Ecol. Sin. 5 (3), 47–52. Tamarix spp. and thus, well-designed clinical trials are needed to con- Bahramsoltani, R., Rahimi, R., Farzaei, M.H., 2017. Pharmacokinetic interactions of firm the safety and efficacy of these plants in human. Future studieson curcuminoids with conventional drugs: a review. J. Ethnopharmacol. 209, 1–12. the phytochemical, pharmacological, and toxicological aspects of Bakr, R.O., El Raey, M.A.E.A., Ashour, R.S., 2013. Phenolic content, radical scavenging activity and cytotoxicity of Tamarix nilotica (Ehrenb.) bunge growing in Egypt. J. Tamarix spp. is needed to provide better knowledge of these valuable Pharmacogn. Phytotherapy 5, 47–52. plants. Barakat, H.H., Nawwar, M.A.M., Buddrus, J., Linscheid, M., 1987. Niloticol, a phenolic glyceride and two phenolic aldehydes from the roots of Tamarix nilotica. Conflicts of interest Phytochemistry 26, 1837–1838. Basas-Jaumandreu, J., López, J., De Las Heras, F.X.C., 2014. Resorcinol and m-guaiacol alkylated derivatives and asymmetrical secondary alcohols in the leaves from Authors declare that they have no conflicts of interest. Tamarix canariensis. Phytochem. Lett. 10, 240–248. Ben Hmidene, A., Hanaki, M., Murakami, K., Irie, K., Isoda, H., Shigemori, H., 2017a. Inhibitory activities of antioxidant flavonoids from tamarix gallica on amyloid ag- Authors contribution gregation related to alzheimer's and type 2 diabetes diseases. Biol. Pharm. Bull. 40, 238–241. MHF & RR designed the study, edited the main text and approved Ben Hmidene, A., Smaoui, A., Abdelly, C., Isoda, H., Shigemori, H., 2017b. Effect of O- methylated and glucuronosylated flavonoids from Tamarix gallica on alpha-glucosi- the final edition of the manuscript. RB & SMAZ performed the search, dase inhibitory activity: structure-activity relationship and synergistic potential. prepared the tables, wrote the main text, and approved the final edition Biosci. Biotechnol. Biochem. 81, 445–448. of the manuscript. MK performed the search, prepared the tables, and Benmerache, A., Benteldjoune, M., Alabdul Magid, A., Abedini, A., Berrehal, D., Kabouche, A., Gangloff, S.C., Voutquenne-Nazabadioko, L., Kabouche, Z., 2017. approved the final version of the manuscript. Chemical composition, antioxidant and antibacterial activities of Tamarix balansae J. Gay aerial parts. Nat. Prod. Res. 31, 2828–2835. Acknowledgement Bettaib, J., Talarmin, H., Droguet, M., Magne, C., Boulaaba, M., Giroux-Metges, M.A., Ksouri, R., 2017. Tamarix gallica phenolics protect IEC-6 cells against H2O2 induced stress by restricting oxidative injuries and MAPKs signaling pathways. Biomed. This study has been partially supported by Tehran University of Pharmacother. 89, 490–498. Medical Sciences; Tehran, Iran. Grant No. 96-04-86-37025. Boulaaba, M., Tsolmon, S., Ksouri, R., Han, J., Kawada, K., Smaoui, A., Abdelly, C., Isoda, H., 2013. Anticancer effect of Tamarix gallica extracts on human colon cancer cells involves Erk1/2 and p38 action on G2/M cell cycle arrest. Cytotechnology 65, References 927–936. Bughio, S.H., Samejo, M.Q., Memon, S., Bano, S., Mughal, M.A., Memon, A.A., 2018. Chemical composition of the essential oils from Tamarix dioica and determination of Abaza, M.S., Al-Attiyah, R., Bhardwaj, R., Abbadi, G., Koyippally, M., Afzal, M., 2013. its antibacterial activity. Int. J. Food Prop. 20, S2660–S2667. Syringic acid from Tamarix aucheriana possesses antimitogenic and chemo-sensi- Cameron, B., Landreth, G.E., 2010. Inflammation, microglia, and Alzheimer's disease. tizing activities in human colorectal cancer cells. Pharm. Biol. 51, 1110–1124. Neurobiol. Dis. 37, 503–509. Abaza, M.S.I., Afzal, M., Al-Attiyah, R.J., Guleri, R., 2016. Methylferulate from Tamarix Chaturvedi, S., Drabu, S., Sharma, M., 2012. Anti- inflammatory and analgesic activity of aucheriana inhibits growth and enhances chemosensitivity of human colorectal Tamarix gallica. Int. J. Pharm. Pharm. Sci. 4, 653–658. cancer cells: possible mechanism of action. BMC Complement Altern. Med. 16 (1), Chen, R., Yang, Y., Xu, J., Pan, Y., Zhang, W., Xing, Y., Ni, H., Sun, Y., Hou, Y., Li, N., 384. 2018. Tamarix hohenackeri Bunge exerts anti-inflammatory effects on lipopoly- Abdul Hakeem, Mohammad, 2002. Bustanul Mufeadat. Idara Kitab-Alshifa, Delhi, pp. saccharide-activated microglia in vitro. Phytomedicine 40, 10–19.

22 R. Bahramsoltani, et al. Journal of Ethnopharmacology 246 (2020) 112245

Coskun, O., Kanter, M., Korkmaz, A., Oter, S., 2005. Quercetin, a flavonoid antioxidant, Khalid, M., Hassani, D., Bilal, M., Butt, Z.A., Hamayun, M., Ahmad, A., Huang, D., prevents and protects streptozotocin-induced oxidative stress and β-cell damage in Hussain, A., 2017. Identification of oral cavity biofilm forming bacteria andde- rat pancreas. Pharmacol. Res. 51, 117–123. termination of their growth inhibition by Acacia arabica, Tamarix aphylla L. and Cummings, J.L., Isaacson, R.S., Schmitt, F.A., Velting, D.M., 2015. A practical algorithm Melia azedarach L. medicinal plants. Arch. Oral Biol. 81, 175–185. for managing Alzheimer's disease: what, when, and why? Ann. Clin. Transl. Neurol. 2, Khan, S., Ullah, F., Mahmood, T., 2013. In vitro antimicrobial and cytotoxic activity of 307–323. Tamarix dioica Roxb. leaves. Turkish. J. Biol. 37, 329–335. de Jesus, N.Z.T., Falcao, H.d.S., Gomes, I.F., Leite, T.J.d.A., Lima, G.R.d.M., Barbosa- Khare, C.P., 2004. Indian Herbal Remedies: Rational Western Therapy, Ayurvedic, and Filho, J.M., Tavares, J.F., Silva, M.S.d., Athayde-Filho, P.F.d., Batista, L.M., 2012. Other Traditional Usage. Springer science & business media, Botany, pp. 444. Tannins, peptic ulcers and related mechanisms. Int. J. Mol. Sci. 13, 3203–3228. Khattak, N.S., Nouroz, F., Rahman, I.U., Noreen, S., 2015. Ethno veterinary uses of De Silva, H.A., Saparamadu, P.A.M., Thabrew, M.I., Pathmeswaran, A., Fonseka, M.M.D., medicinal plants of district Karak, Pakistan. J. Ethnopharmacol. 171, 273–279. De Silva, H.J., 2003. Liv.52 in alcoholic liver disease: a prospective, controlled trial. Khorasani, M.H.A., Makhzan-al-Adviah, 1771. 124. Tehran University of Medical J. Ethnopharmacol. 84, 47–50. Sciences, pp. 529 2009. Dudareva, N., Pichersky, E., Gershenzon, J., 2004. Biochemistry of plant volatiles. Plant Kim, H.P., Son, K.H., Chang, H.W., Kang, S.S., 2004. Anti-inflammatory plant flavonoids Physiol. 135, 1893–1902. and cellular action mechanisms. J. Pharmacol. Sci. 96 (3), 229–245. El Ansari, M.A., Nawwar, M.A.M., El Dein, A., El Sherbeiny, A., El Sissi, H.I., 1976. A Ksouri, R., Falleh, H., Megdiche, W., Trabelsi, N., Mhamdi, B., Chaieb, K., Bakrouf, A., sulphated kaempferol 7,4′-dimethyl ether and a quercetin isoferulylglucuronide from Magne, C., Abdelly, C., 2009. Antioxidant and antimicrobial activities of the edible the flowers of Tamarix aphylla. Phytochemistry 15, 231–232. medicinal halophyte Tamarix gallica L. and related polyphenolic constituents. Food El Sissi, H.I., Nawwar, M.A.M., Saleh, N.A.M., 1973. Plant constituents of Tamarix nilo- Chem. Toxicol. 47, 2083–2091. tica leaves (Tamaricaceae). Experientia 29, 1064–1065. Law, M.E., Corsino, P.E., Narayan, S., Law, B.K., 2015. Cyclin-dependent kinase inhibitors El-Mousallami, A.M.D., Hussein, S.A.M., Nawwar, M.A.M., 2000. Polyphenolic metabo- as anticancer therapeutics. Mol. Pharmacol. 88, 846–852. lites of the flowers of Tamarix tetragyna. Nat. Prod. Sci. 6, 193–198. Lefahal, M., Benahmed, M., Louaar, S., Zallagui, A., Duddeck, H., Medjroubi, K., Akkal, S., Fallah Huseini, H., Alavian, S.M., Heshmat, R., Heydari, M.R., Abolmaali, K., 2005. The 2010. Antimicrobial activity of Tamarix gallica L. Extracts and isolated flavonoids. efficacy of Liv-52 on liver cirrhotic patients: a randomized, double-blind, placebo- Adv. Nat. Applied. Sci. 4, 289–292. controlled first approach. Phytomedicine 12, 619–624. Mahfoudhi, A., Prencipe, F.P., Mighri, Z., Pellati, F., 2014. Metabolite profiling of poly- Fellah, O., Hameurlaine, S., Gherraf, N., Zellagui, A., Ali, T., Abidi, A., Altun, M., phenols in the Tunisian plant Tamarix aphylla (L.) Karst. J. Pharm. Biomed. Anal. 99, Demirtas, I., SahinYaglioglu, A., 2018. Anti-proliferative activity of ethyl acetate 97–105. extracts of Tamarix gallica L. grown at different climatic conditions in Algeria. Acta. Mahfoudhi, A., Grosso, C., Gonçalves, R.F., Khelifi, E., Hammami, S., Achour, S., Trabelsi- Scientifica. Naturalis. 5, 23–31. Ayadi, M., Valentão, P., Andrade, P.B., Mighri, Z., 2016. Evaluation of antioxidant, Government of India, Ministry og Health and Family Welfare, 2009. The Unani anticholinesterase, and antidiabetic potential of dry leaves and stems in tamarix Pharmacopoeia of India, vol. vol. I. Department of Ayurveda, Yoga & Naturopathy, aphylla growing wild in Tunisia. Chem. Biodivers. 13, 1747–1755. Unani, Siddha and Homeopathy (AYUSH), Ministry of Health and Family Welfare, Mahmood, A., Mahmood, A., Shaheen, H., Qureshi, R.A., Sangi, Y., Gilani, S.A., 2011. Government of India Red Cross Building, New Delhi, pp. 51 Part I. Ethno medicinal survey of plants from district Bhimber Azad Jammu and Kashmir, Habiba, U., Bose, U., Rahman, A.A., 2010. Antinociceptive, antidiarrhoeal and cytotoxic Pakistan. J. Med. Plants Res. 5, 2348–2360. activity of Tamarix indica leaf. Pharmacologyonline 1, 275–283. Maleki, M., Djazayeri, M., 1972. Chemical characteristics and composition of „gaz” gum Hammiche, V., Maiza, K., 2006. Traditional medicine in central sahara: pharmacopoeia of from tamarix manifera. Starch ‐ Stärke 24, 296–299. tassili N'ajjer. J. Ethnopharmacol. 105, 358–367. Mandeel, Q., Taha, A., 2005. Assessment of in vitro antifungal activities of various ex- Han, Z., Yin, W., Zhang, J., Niu, S., Ren, L., 2013. Active anti-erosion protection strategy tracts of indigenous Bahraini medicinal plants. Pharm. Biol. 43, 340–348. in Tamarisk (Tamarix aphylla). Sci. Rep. 3, 3429. McGrath, J.C., Lilley, E., 2015. Implementing guidelines on reporting research using Hassan, L.E.A., Khadeer Ahamed, M.B., Abdul Majid, A.S., Baharetha, H.M., Muslim, N.S., animals (ARRIVE etc.): new requirements for publication in BJP. Br. J. Pharmacol. Nassar, Z.D., Abdul Majid, A.M.S., 2014. Correlation of antiangiogenic, antioxidant 172 (13), 3189–3193. and cytotoxic activities of some Sudanese medicinal plants with phenolic and fla- Merfort, I., Buddrus, J., Nawwar, M.A.M., Lambert, J., 1992. A triterpene from the bark of vonoid contents. BMC Complement Altern. Med. 14, 206. Tamarix aphylla. Phytochemistry 31, 4031–4032. Hebi, M., Eddouks, M., 2017a. Hypolipidemic activity of Tamarix articulata Vahl. in Miara, M.D., Bendif, H., Rebbas, K., Rabah, B., Hammou, M.A., Maggi, F., 2019. diabetic rats. J. Integr. Med. 15, 476–482. Medicinal plants and their traditional uses in the highland region of Bordj Bou Hebi, M., Farid, O., Ajebli, M., Eddouks, M., 2017. Potent antihyperglycemic and hy- Arreridj (Northeast Algeria). J. Herb. Med. https://doi.org/10.1016/j.hermed.2019. poglycemic effect of Tamarix articulata Vahl. in normal and streptozotocin-induced 100262. diabetic rats. Biomed. Pharmacother. 87, 230–239. Moghanloo, L., Ghahremani Nezhad, F., Vafadar, M., 2019. Ethnobotanical study of Hebi, M., Hajji, L., Eddouks, M., 2018. Effect of flavonoid-rich extract of tamarix ar- medicinal plants in the central district of the Zanjan county, Zanjan province, Iran. J. ticulata Vahl. On glucose and lipid metabolism in normal and diabetic rats. Herb. Drugs. 9, 121–131. Cardiovasc. Hematol. Agents Med. Chem. 16 (2), 94–105. Mohieldin, E.A.M., Muddathir, A.M., Mitsunaga, T., 2017. Inhibitory activities of selected Hollman, P.C., van Trijp, J.M., Buysman, M.N., van der Gaag, M.S., Mengelers, M.J., de Sudanese medicinal plants on Porphyromonas gingivalis and matrix metalloprotei- Vries, J.H., Katan, M.B., 1997. Relative bioavailability of the antioxidant flavonoid nase-9 and isolation of bioactive compounds from Combretum hartmannianum quercetin from various foods in man. FEBS Lett. 418 (1–2), 152–156. (Schweinf) bark. BMC Complement Altern. Med. 17 (1), 224. Hong, Z., Li, J., Biswas, S., Jiang, C.S., Huang, Y., Sun, T., Niu, Y., Yu, J.Q., Li, W.Q., Yao, Muhammad, H., Wazir, S.M., Khan, R.A., 2017. In vitro antioxidant, antifungal and cy- Y., 2018. Ramosissimin, a new flavonol from Tararix ramosissima, induces apoptosis totoxic activities of selected medicinal plants of district bannu and lakki marwat. in rheumatoid arthritis fibroblast-like synoviocytes. Die Pharmazie 73, 169–173. Ethno. Med 11 (2), 26–232. Hunter, P., 2012. The inflammation theory of disease: the growing realization that Nadkarni, K., 1976. Indian Materia Medica. Popular Publication, Bombay, pp. chronic inflammation is crucial in many diseases opens new avenues for treatment. 1193–1195. EMBO Rep. 13, 968–970. Nawwar, M.A.M., Hussein, S.A.M., 1994. Gall polyphenolics of Tamarix aphylla. Hussein, S.A.M., 1997. New dimeric phenolic conjugates from the wood of Tamarix tet- Phytochemistry 36, 1035–1037. ragyna. Nat. Prod. Sci. 3, 127–134. Nawwar, M.A.M., Souleman, A.M.A., 1984. 3,4,8,9,10-Pentahydroxy-dibenzo[b,d]pyran- Ishak, M.S., el-Sissi, H.I., el-Sherbieny, A.E., Nawwar, M.A., 1972a. Tannins and poly- 6-one from Tamarix nilotica. Phytochemistry 23, 2966–2967. phenolics of the galls of Tamarix aphylla. II. Planta Med. 21, 374–381. Nawwar, M.A.M., El Sherbeiny, A.E.A., El Ansari, M.A., 1975. Plant constitutents of Ishak, M.S., el-Sissi, H.I., Nawwar, M.A., el-Sherbieny, A.E., 1972b. Tannins and poly- Tamarix aphylla flowers (Tamaricaceae). Experientia 31 1118-1118. phenolics of the galls of Tamarix aphylla. I. Planta Med. 21, 246–253. Nawwar, M.A.M., Buddrus, J., Bauer, H., 1982. Dimeric phenolic constituents from the Jaeschke, H., McGill, M.R., Ramachandran, A., 2012. Oxidant stress, mitochondria, and roots of Tamarix nilotica. Phytochemistry 21, 1755–1758. cell death mechanisms in drug-induced liver injury: lessons learned from acet- Nawwar, M.A.M., Souleman, A.M.A., Buddrus, J., Bauer, H., Linscheid, M., 1984a. aminophen hepatotoxicity. Drug Metab. Rev. 44, 88–106. Polyphenolic constituents of the flowers of Tamarix nilotica: the structure of nilocitin, Jdey, A., Falleh, H., Ben Jannet, S., Mkadmini Hammi, K., Dauvergne, X., Ksouri, R., a new digalloylglucose. Tetrahedron Lett. 25, 49–52. Magné, C., 2017. Phytochemical investigation and antioxidant, antibacterial and Nawwar, M.A.M., Souleman, A.M.A., Buddrus, J., Linscheid, M., 1984b. Flavonoids of the anti-tyrosinase performances of six medicinal halophytes. South Afr. J. Bot. 112, flowers of tamarix nilotica. Phytochemistry 23, 2347–2349. 508–514. Nawwar, M.A.M., Hussein, S.A.M., Buddrus, J., Linscheid, M., 1994. Tamarixellagic acid, Jedinak, A., Valachova, M., Maliar, T., Sturdik, E., 2010. Antiprotease activity of selected an ellagitannin from the galls of Tamarix aphylla. Phytochemistry 35, 1349–1354. Slovak medicinal plants. Die Pharmazie 65, 137–140. Nawwar, M.A., Hussein, S.A., Ayoub, N.A., Hofmann, K., Linscheid, M., Harms, M., Kabiruddin, 2000. Makhzanul Mufradat. YNM. Ejaz Publishing House, Delhi, pp. Wende, K., Lindequist, U., 2009. Aphyllin, the first isoferulic acid glycoside and other 228–229. phenolics from Tamarix aphylla flowers. Die Pharmazie 64, 342–347. Kahkeshani, N., Farzaei, F., Fotouhi, M., Alavi, S.S., Bahramsoltani, R., Naseri, R., Orabi, M.A., Taniguchi, S., Hatano, T., 2009. Monomeric and dimeric hydrolysable tan- Momtaz, S., Abbasabadi, Z., Rahimi, R., Farzaei, M.H., 2019. Pharmacological effects nins of Tamarix nilotica. Phytochemistry 70, 1286–1293. of gallic acid in health and disease: a mechanistic review. Iran. J. Basic. Med. Sci. 22, Orabi, M.A., Taniguchi, S., Yoshimura, M., Yoshida, T., Kishino, K., Sakagami, H., Hatano, 225–237. T., 2010a. Hydrolyzable tannins of tamaricaceous plants. III. Hellinoyl- and macro- Karker, M., De Tommasi, N., Smaoui, A., Abdelly, C., Ksouri, R., Braca, A., 2016. New cyclic-type ellagitannins from Tamarix nilotica. J. Nat. Prod. 73, 870–879. sulphated flavonoids from tamarix africana and biological activities of its polarex- Orabi, M.A.A., Taniguchi, S., Yoshimura, M., Yoshida, T., Hatanoa, T., 2010b. New tract. Planta Med. 82, 1374–1380. monomeric and dimeric hydrolyzable tannins from Tamarix nilotica. Heterocycles Keymanesh, K., Hamedi, J., Moradi, S., Mohammadipanah, F., Sardari, S., 2009. 80, 463–475. Antibacterial, antifungal and toxicity of rare Iranian plants. Int. J. Pharmacol. 5, Orabi, M.A., Taniguchi, S., Terabayashi, S., Hatano, T., 2011. Hydrolyzable tannins of 81–85. tamaricaceous plants. IV: micropropagation and ellagitannin production in shoot

23 R. Bahramsoltani, et al. Journal of Ethnopharmacology 246 (2020) 112245

cultures of Tamarix tetrandra. Phytochemistry 72, 1978–1989. Shanna, S., Parmar, V., 1998. Novel constituents of Tamarix species. J. Sci. Ind. Res. 57, Orabi, M.A., Taniguchi, S., Sakagami, H., Yoshimura, M., Yoshida, T., Hatano, T., 2013. 873–890. Hydrolyzable tannins of tamaricaceous plants. V. Structures of monomeric-trimeric Soltan, M.M., Zaki, A.K., 2009. Antiviral screening of forty-two Egyptian medicinal tannins and cytotoxicity of macrocyclic-type tannins isolated from Tamarix nilotica plants. J. Ethnopharmacol. 126, 102–107. (1). J. Nat. Prod. 76, 947–956. Souleman, A.A.M., Barakat, H.H., Hussein, S.A.M., El-Mousallamy, A., Nawwar, M.A.M., Orabi, M.A.A., Yoshimura, M., Amakura, Y., Hatano, T., 2015. Ellagitannins, gallotannins, 1998. Unique phenolic sulphate conjugates from the flowers of Tamarix amplex- and gallo-ellagitannins from the galls of Tamarix aphylla. Fitoterapia 104, 55–63. icaulis. Nat. Prod. Sci. 4, 245–252. Orfali, R.S., Ebada, S.S., El-Shafae, A.M., Al-Taweel, A.M., Lin, W.H., Wray, V., Proksch, Souliman, A.M.A., Barakat, H.H., El-Mousallamy, A.M.D., Marzouk, M.S.A., Nawwar, P., 2009. 3-O-trans-caffeoylisomyricadiol: a new triterpenoid from Tamarix nilotica M.A.M., 1991. Phenolics from the bark of Tamarix aphylla. Phytochemistry 30, growing in Saudi Arabia. Z. Naturforschung C 64, 637–643. 3763–3766. Pandey, K.B., Rizvi, S.I., 2009. Plant polyphenols as dietary antioxidants in human health Soummane, H., Larhsini, M., Naamani, K., Coll, J., 2011. Studies of larvicidal and adul- and disease. Oxid. Med. Cell. Longev. 2, 270–278. ticidal activities of some halophyte plant extracts against Ceratitis capitata Panza, F., Lozupone, M., Logroscino, G., Imbimbo, B.P., 2019. A critical appraisal of (Wiedemann). J. Entomol. 8, 548–556. amyloid-β-targeting therapies for Alzheimer disease. Nat. Rev. Neurol. 15 (2), 73–88. Sultanova, N., Makhmoor, T., Abilov, Z.A., Parween, Z., Omurkamzinova, V.B., ur- Parmar, V.S., Rathore, J.S., Singh, S., Jain, A.K., Gupta, S.R., 1985. Troupin, a 4-me- Rahman, A., Choudhary, M.I., 2001. Antioxidant and antimicrobial activities of thylcoumarin from tamarix troupii. Phytochemistry 24, 871–872. Tamarix ramosissima. J. Ethnopharmacol. 78, 201–205. Parmar, V.S., Bisht, K.S., Sharma, S.K., Jain, R., Taneja, P., Singh, S., Simonsen, O., Boll, Sultanova, N.A., Abilov, Z.A., Omurkamzinova, V.B., Chaudri, I.M., 2002. Flavonoids of P.M., 1994. Highly oxygenated bioactive flavones from Tamarix. Phytochemistry 36, the aerial part of Tamarix hispida. Chem. Nat. Compd. 38, 98–99. 507–511. Sultanova, N., Makhmoor, T., Yasin, A., Abilov, Z.A., Omurkamzinova, V.B., Atta ur, R., Pragasam, S.J., Venkatesan, V., Rasool, M., 2013. Immunomodulatory and anti-in- Choudhary, M.I., 2004a. Isotamarixen - a new antioxidant and prolyl endopeptidase- flammatory effect of p-coumaric acid, a common dietary polyphenol on experimental inhibiting triterpenoid from Tamarix hispida. Planta Med. 70, 65–67. inflammation in rats. Inflammation 36, 169–176. Sultanova, N.A., Abilov, Z.A., Shul'ts, E.E., Omurkamzinova, V.B., 2004b. Biologically Qadir, M.I., Abbas, K., Hamayun, R., Ali, M., 2014. Analgesic, anti-inflammatory and anti- active compounds from Tamarix hispida. II. Chem. Nat. Compd. 40, 192–193. pyretic activities of aqueous ethanolic extract of Tamarix aphylla L. (Saltcedar) in Sultanova, N.A., Abilov, Z.A., Umbetova, A.K., Choudhary, M.I., 2013. Biologically active mice. Pakistan. J. Pharmaceut. Sci. 27, 1985–1988. terpenoids from Tamarix species. Eurasian. Chemico-Technol. J. 15, 219–226. Quattrocchi, U., 2016. CRC World Dictionary of Medicinal and Poisonous Plants: Tabassum, N., Chatturvedi, S., Agrawal, S.S., 2006. Effect of Tamarix gallica leaves on Common Names, Scientific Names, Eponyms, Synonyms, and Etymology (5 Volume experimental liver cell injury. JK Pract. 13, 43–44. Set). CRC press. Tahraoui, A., El-Hilaly, J., Israili, Z.H., Lyoussi, B., 2007. Ethnopharmacological survey of Rahimi, R., Nikfar, S., Larijani, B., Abdollahi, M., 2005. A review on the role of anti- plants used in the traditional treatment of hypertension and diabetes in south-eastern oxidants in the management of diabetes and its complications. Biomed. Morocco (Errachidia province). J. Ethnopharmacol. 110, 105–117. Pharmacother. 59, 365–373. Tomás-Barberán, F.A., Iniesta-Sanmartín, E., Ferreres, F., Tomas-Lorente, F., Trowitzsch- Rahman, M.A., Haque, E., Hasanuzzaman, M., Shahid, I.Z., 2011. Antinociceptive, anti- Kienastt, W., Wray, V., 1990. Trans-coniferyl alcohol 4-o-sulphate and flavonoid inflammatory and antibacterial properties of tamarix indica roots. Int. J. Pharmacol. sulphates from some Tamarix species. Phytochemistry 29, 3050–3051. 7, 527–531. Ullah, S., Rashid Khan, M., Ali Shah, N., Afzal Shah, S., Majid, M., Asad Farooq, M., 2014. Ramar, M., Manikandan, B., Raman, T., Priyadarsini, A., Palanisamy, S., Velayudam, M., Ethnomedicinal plant use value in the lakki marwat district of Pakistan. J. Munusamy, A., Prabhu, N.M., Vaseeharan, B., 2012. Protective effect of ferulic acid Ethnopharmacol. 158, 412–422. and resveratrol against alloxan-induced diabetes in mice. Eur. J. Pharmacol. 690, Ullah, R., Tariq, S.A., Khan, N., Sharif, N., Ud Din, Z., Mansoor, K., 2017. 226–235. Antihyperglycemic effect of methanol extract of Tamarix aphylla L. Karst (Saltcedar) Rasouli, H., Farzaei, M.H., Khodarahmi, R., 2017. Polyphenols and their benefits: a re- in streptozocin–nicotinamide induced diabetic rats. Asian. Pac. J Trop. Biomed. 7, view. Int. J. Food Prop. 20, 1700–1741. 619–623. Razi, M.I.Z., 2005. The great continens (Alhavi-fil-Tib).Transaleted by afsharipour. S. Umair, M., Altaf, M., Bussmann, R.W., Abbasi, A.M., 2019. Ethnomedicinal uses of the Tehran: Academy of Medical Sciences Islamic Republic of Iran 101 ([Persian local flora in Chenab riverine area, Punjab province Pakistan. J. Ethnobiol. Translation]). Ethnomed. 15, 7. Reagan-Shaw, S., Nihal, M., Ahmad, N., 2008. Dose translation from animal to human Umbetova, A.K., Choudhary, M.I., Sultanova, N.A., Burasheva, G.S., Abilov, Z.A., 2005. studies revisited. FASEB J. 22 (3), 659–661. Flavonoids of plants from the genus Tamarix. Chem. Nat. Compd. 41, 728–729. Ren, X., Bao, Y., Zhu, Y., Liu, S., Peng, Z., Zhang, Y., Zhou, G., 2019. Isorhamnetin, Umbetova, A.K., Choudhary, M.I., Sultanova, N.A., Burasheva, G.S., Abilov, Z.A., 2006. hispidulin, and cirsimaritin identified in tamarix ramosissima barks from southern Triterpenoids from plants of the genus Tamarix. Chem. Nat. Compd. 42, 332–335. Xinjiang and their antioxidant and antimicrobial activities. Molecules 24 (3), E390. Urfi, M.K., Mujahid, M., Rahman, M.A., Rahman, M.A., 2018. The role of tamarix gallica Rezaeiamiri, E., Bahramsoltani, R., Rahimi, R., 2019. Plant-derived natural agents as leaves extract in liver injury induced by rifampicin plus isoniazid in sprague dawley dietary supplements for the regulation of glycosylated hemoglobin: a review of rats. J. Diet. Suppl. 15, 24–33. clinical trials. Clin. Nutr. pii: S0261- 5614 (19). https://doi.org/10.1016/j.clnu.2019. Utkin, L.M., 1966. The structure of tamarixin. Chem. Nat. Compd. 2, 128–130. 02.006. 30058-5. Whitcraft, C.R., Talley, D.M., Crooks, J.A., Boland, J., Gaskin, J., 2007. Invasion of ta- Riaz, U., Sadiq, N., Tahir, M., Rajpoot, N.N., Ali, A., 2018. Hepatoprotective effect of marisk (Tamarix spp.) in a southern California salt marsh. Biol. Invasions 9, 875–879. tamarix dioica roots on acetaminophen induced hepatotoxicity in male mice. J. Wu, C., 2014. An important player in brine shrimp lethality bioassay: the solvent. J. Adv. Islamic. Int. Med. College. 13 (4), 189–193. Pharm. Technol. Research (JAPTR) 5, 57. Robbins, R.J., 2003. Phenolic acids in foods: an overview of analytical methodology. J. Xiao, L.P., Shi, Z.J., Xu, F., Sun, R.C., 2013. Characterization of lignins isolated with Agric. Food Chem. 51, 2866–2887. alkaline ethanol from the hydrothermal pretreated tamarix ramosissima. Bioenergy. Saidana, D., Mahjoub, M.A., Boussaada, O., Chriaa, J., Cheraif, I., Daami, M., Mighri, Z., Res. 6, 519–532. Helal, A.N., 2008. Chemical composition and antimicrobial activity of volatile Xing, Y., Liao, J., Tang, Y., Zhang, P., Tan, C., Ni, H., Wu, X., Li, N., Jia, X., 2014. ACE and compounds of Tamarix boveana (Tamaricaceae). Microbiol. Res. 163, 445–455. platelet aggregation inhibitors from Tamarix hohenackeri Bunge (host plant of Herba Saleh, N.A.M., El-Sissi, H.I., Nawwar, M.A.M., 1975. A rhamnetin glucuronide trisulphate Cistanches) growing in Xinjiang. Pharmacogn. Mag. 10, 111–117. from the leaves of Tamarix aphylla. Phytochemistry 14, 312–313. Yao, Y., Jiang, C.S., Sun, N., Li, W.Q., Niu, Y., Han, H.Q., Miao, Z.H., Zhao, X.X., Zhao, J., Salissou, M., Mahaman, Y., Zhu, F., Huang, F., Wang, Y., Xu, Z., Ke, D., Wang, Q., Liu, R., Li, J., 2017. Tamaractam, a new bioactive lactam from tamarix ramosissima, induces Wang, J., 2018. Methanolic extract of Tamarix Gallica attenuates hyperhomocystei- apoptosis in rheumatoid arthritis fibroblast-like synoviocytes. Molecules 22 (1), E96. nemia induced AD-like pathology and cognitive impairments in rats. Aging 10 (11), https://doi.org/10.3390/molecules22010096. 3229–3248. Yaseen, G., Ahmad, M., Zafar, M., Sultana, S., Kayani, S., Cetto, A.A., Shaheen, S., 2015. Samadi, N., Ghaffari, S.M., Akhani, H., 2013. Meiotic behaviour, karyotype analyses and Traditional management of diabetes in Pakistan: ethnobotanical investigation from pollen viability in species of Tamarix (Tamaricaceae). Willdenowia 43 (1), 195–203. traditional health practitioners. J. Ethnopharmacol. 174, 91–117. Sehrawat, A., Sultana, S., 2006a. Evaluation of possible mechanisms of protective role of Yoshida, T., Ahmed, A.F., Memon, M.U., Okuda, T., 1991. Tannins of tamaricaceous Tamarix gallica against DEN initiated and 2-AAF promoted hepatocarcinogenesis in plants: II: new monomeric and dimeric hydrolyzable tannins from reaumuria hirtella male Wistar rats. Life Sci. 79, 1456–1465. and tamarix pakistanica. Chem. Pharm. Bull. 39, 2849–2854. Sehrawat, A., Sultana, S., 2006b. Tamarix gallica ameliorates thioacetamide-induced Yoshida, T., Ahmed, A.H.F., Memon, M.U., Okuda, T., 1993. Dimeric hydrolysable tannins hepatic oxidative stress and hyperproliferative response in Wistar rats. J. Enzym. from Tamarix pakistanica. Phytochemistry 33, 197–202. Inhib. Med. Chem. 21, 215–223. Yusufoglu, H.S., Alqasoumi, S.I., 2011. Anti-inflammatory and wound healing activities of Sekkien, A., Swilam, N., Ebada, S.S., Esmat, A., El-Khatib, A.H., Linscheid, M.W., Singab, herbal gel containing an antioxidant tamarix aphylla leaf extract. Int. J. Pharmacol. A.N., 2018. Polyphenols from Tamarix nilotica: LC–ESI-MSn profiling and in vivo 7, 829–835. antifibrotic activity. Molecules 23 (6), E1411. https://doi.org/10.3390/ Zaidi, S.F., Muhammad, J.S., Shahryar, S., Usmanghani, K., Gilani, A.H., Jafri, W., molecules23061411. pii. Sugiyama, T., 2012. Anti-inflammatory and cytoprotective effects of selected Shah, A., Rahim, S., Bhatti, K.H., Khan, A., Din, N., Imran, M., Mohsin, M., Ishtiaq, M., Pakistani medicinal plants in Helicobacter pylori-infected gastric epithelial cells. J. Nabila, A., Ansari, A., Hussain, S., Zafar, M., Mushtaq, M., Mumtaz, E., Iqbal, J., Ethnopharmacol. 141, 403–410. 2015. Ethnobotanical study and conservation status of trees in the district Sargodha, Zhang, D., Yin, L., Pan, B., 2002. Biological and ecological characteristics ofTamarix L. Punjab, Pakistan. Phyton 84, 34–44. and its effect on the ecological environment. Sci. China Ser. D Earth Sci. 42,18–22.