Hindawi Evidence-Based Complementary and Alternative Medicine Volume 2018, Article ID 8426752, 21 pages https://doi.org/10.1155/2018/8426752

Research Article Antiobesity and Antioxidant Potentials of Selected Palestinian Medicinal Plants

Rana M. Jamous , Salam Y. Abu-Zaitoun, Rola J. Akkawi, and Mohammed S. Ali-Shtayeh Biodiversity and Environmental Research Center (BERC), Til, Nablus, State of Palestine

Correspondence should be addressed to Mohammed S. Ali-Shtayeh; [email protected]

Received 25 February 2018; Revised 9 May 2018; Accepted 15 May 2018; Published 13 June 2018

Academic Editor: Daniela Rigano

Copyright © 2018 Rana M. Jamous et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

We evaluated the antioxidant and porcine pancreatic lipase inhibition (PPLI) activities of 90 plants extracts. Te antioxidant activity was measured using the free-radical scavenging capacity (DPPH) and reducing power (RP) assays. Te pancreatic lipase inhibition assay was used to determine the PPLI activity of plant extracts. Among the 90 plant extracts examined, 41.0 % crude extracts showed antilipase activity of more than 50%. Te most active plants by means of IC50 value were Camellia sinensis (0.5 mg/ml), Ceratonia siliqua (leaves) (0.8 mg/mL), Curcuma longa (0.8 mg/mL), Sarcopoterium spinosum (1.2 mg/mL), and Mentha spicata (1.2 mg/mL). Te antioxidant activity of plant extracts using the DPPH and RP assays reveals comparable results. Te most active antioxidant extracts using both assays were the leaves and fruit epicarp of Rhus coriaria,arealpartsofSarcopoterium spinosum,andleavesof Ceratonia siliqua. Our results suggest natural resources that possess strong antioxidant and pancreatic lipase inhibitory activities with potential applications in the treatment and prevention of obesity and overweight. Te extracts of Camellia sinensis, Ceratonia siliqua, Curcuma longa, Sarcopoterium spinosum, and Mentha spicata were proved to have a great potential as antioxidants and antiobesity agents.

1. Introduction of these over 650 million were obese. Over 340 million children and adolescents aged 5-19 were overweight or obese, Overweight and obesity are defned as abnormal or excessive while 41 million children under the age of 5 were overweight fat accumulation that may impair health. Body mass index or obese in 2016. Most of the world's population lives in (BMI)isacrudepopulationmeasureofobesitythatis countries where overweight and obesity kill more people commonly used to classify overweight and obesity in adults; than underweight; obesity has reached epidemic proportions it is defned as a person’s weight in kilograms divided by the globally, with about 2.8 million people dying each year as a square of their height in meters (kg/m2). A person with a BMI result of being overweight or obese [1]. of 30 or more is generally considered obese, while a person Overweight and obesity were once considered a high- with a BMI equal to or more than 25 is considered overweight income countries problem; however, it is now also prevalent [1]. in low- and middle-income countries [1]. Te factors leading Te prevalence of obesity difers from one country to to this widespread increase in obesity have been suggested to another and depends on several factors including gender, include economic growth, modernization, westernization of age, educational accomplishment, annual household income, lifestyles (high calorie diet including processed foods higher employment status, and social class [2, 3]. Obesity is consid- in fats and refned sugars and decrease in exercise levels), ered an extremely costly health problem, the direct medical and the globalization of food markets [5, 6]. Other factors cost of overweight and obesity combined is approximately mayalsocontributetothisproblemincludingfamilialsus- 5.0% to 10% of US health care spending [4]. ceptibility, endocrine disorders, and environmental factors According to the recent WHO report, more than 1.9 [7], with women being suggested to be especially at risk billion adults, 18 years and older, were overweight in 2016, [8, 9]. 2 Evidence-Based Complementary and Alternative Medicine

In Palestine, the prevalence of overweight and obesity nonnutrient biologically active phytochemicals including was estimated as 58.7% and 71.3% among men and women, polyphenols and anthocyanins, which are involved in a wide respectively[10].Tiscanbeattributedtoseveralfactors range of health benefts such as decreasing the rates of cardio- including decreased physical activity, increased consumption vascular diseases, lowering the risk of cancer, stroke, and type of high caloric foods, particularly with an increase in energy 2 diabetes, and preventing obesity [28, 29]. Antioxidant-rich coming from fat, smoking, and urbanization [11]. A cross- fruits help in the prevention of free-radical induced oxidative sectional study was carried out in Palestine to investigate the stress [30–32]. prevalence of overweight and obesity among school children Plant derived products may also contain phytochemicals aged from 6-12 years. Te study revealed that the prevalence that act as enzyme inhibitors [33]. Tese compounds have of overweight and obesity among male students was 13.3% the ability to bind to enzymes and inhibit their activity. and 7.9%, respectively, while it was 13.6% and 4.9% among Te presence of inhibitors of carbohydrate and glycerides female students, respectively [12]. hydrolyzing enzymes such as �-glucosidase, �-amylase, and Diferent powerful synthetic chemical drugs used against lipase in plant derived products helps in the control of blood obesity are available in the pharmaceutical market; the FDA glucose level in patients with type 2 diabetes and to prevent has approved fve prescription medications for long-term obesity [20, 34]. use for the treatment of overweight and obesity, includ- Knowledge of herbs has been inherited and transferred ing orlistat, lorcaserin, phentermine-topiramate, naltrexone- from generation to generation for thousands of years. In bupropion, and liraglutide [13]. However, the cost of these Palestine as in many other countries herbal medicine is still products generally keeps them out of reach of most people; the primary form of therapy in the practiced traditional more importantly, many of these products have adverse medical systems [35–39]. Tree hundred ninety-six plant side efects including cardiovascular events and strokes, specieshavebeenreportedtobeusedinTraditionalArabic coughing, dizziness, mouth dryness, anxiousness, fatigue, Palestinian Herbal Medicine (TAPHM) for the treatment of fatulence, headache, insomnia, leakage of oily stools, nausea, various diseases [40]; of these 39 plants were reported to be and hepatic adverse efects [14–17]. Tat is the reason for used for the treatment of obesity [41] (Table 1). Accordingly, the withdrawal from the market of some older drugs such the aim of this study was to evaluate in vitro the antioxidant as Sibutral, rimonabant, isomeride, ponderal, and Xenical and PPL inhibitory activities of some Palestinian medicinal [16, 18]. Hence, the use of naturally occurring inhibitors is plants that have been reported in TAPHM for the treatment considered to be safer [19]. of obesity and other chronic diseases and to explore newly Pancreatic lipase plays a key role in the efcient digestion potent and safe natural therapeutic agents for the treatment of triglycerides [20]. Lipases are involved in the hydrolysis of obesity. of glycerides to glycerol and free fatty acids. Te enzyme inhibition is one of the approaches used to treat obesity due 2. Materials and Methods to the fact that 50-70 % of total dietary fat hydrolysis was performed by pancreatic lipase [21].Te mechanism involves 2.1. Plant Materials. Plants material were either collected inhibition of dietary triglyceride absorption, as this is the from Nablus area in Northern Palestine or purchased from main source of excess calories [22]. Besides, pancreatic lipase traditional drug stores (Attarin Shops) in Nablus city. Tax- inhibition does not alter any central mechanism which makes onomic identifcation of the plant materials was kindly it an ideal approach for obesity treatment [23]. Tis enzyme confrmedbyProfessorM.S.Ali-Shtayeh,plantbiologist, has been widely used for the determination of the potential BERC. Te voucher specimens have been deposited at the efcacy of natural products as antiobesity agents [15]. Orlistat HerbariumoftheBiodiversity&BiotechnologyResearch is the synthetic clinically approved drug used for obesity Institute,BERC,Til,Nablus,Palestine. management. Tis molecule acts by the inhibition of PL Seventy-eight plant species used in TAPHM, of which activity and reduction of triglyceride absorption, and its long- 39 species were reported to be used for the treatment of term administration accompanying an energy restricted diet obesity (Table 1) [41], have been analyzed in this study for resultsinweightloss[24]. their antioxidant and pancreatic lipase inhibition potentials. Te impact of overweight and obesity from a public health Plant parts were dried in the shade, ten grams from each dried perspective is enormous and continue to increase. Numerous material was ground and incubated separately with 100 ml ∘ studies have verifed the association of overweight and of 70% ethanol at 35 C for 3 hours. Te extracts were then ∘ obesity in the development of diferent metabolic disorders fltered and evaporated under vacuum at 50 Ctodryness.Te ∘ including diabetes mellitus, atherosclerosis, cardiovascular powdered extracts were stored at −20 Cforfurtheranalyses. diseases, hypertension, and cancer [25–27]. It is therefore essential to develop ways of preventing more people from 2.2. Pancreatic Lipase Inhibition Assay becoming obese by fnding natural inhibitors of digestion and absorption of dietary lipids which reduce energy intake 2.2.1. Lipase Preparation. Te enzyme solution was prepared through gastrointestinal mechanisms without altering any immediately before use following the method described by main mechanisms [22]. Bustanji et al. [42] with some modifcations. Crude porcine Plant derived products (fruits and vegetables) constitute pancreatic lipase type II (Sigma, USA, EC 3.1.1.3) was sus- an important part of the human diet all over the world and pended in 20 mM tris-HCl bufer pH 8 to give a concentration provide nutrients that are essential for life. Plants contain of 10 mg/ml. Te suspension was mixed using a stirrer for Evidence-Based Complementary and Alternative Medicine 3

Table 1: Plants used in Traditional Arabic Palestinian Herbal Medicine for the treatment of obesity.

Plant Derived Product (Family) English Common Name Plant Part Mode of Preparation (i) A decoction is prepared from the plant; take 1 cup Alchemilla xanthochlora Rothm. twice daily. (Alchemilla vulgaris auct.) Lion’s Foot, Lady’s – Mantle AP (ii) A decoction is prepared from plant mixed with (Rosaceae) rosemary, and wild thyme. 1-2 cups are taken daily (i)Add1teaspoonoftheplantjuicetoacupoffruit Allium cepa L. (Liliaceae) Onion FLE juice to sweeten the taste, and drink 1 cup daily Allium sativum L. (Liliaceae) Garlic GLV (i) Eaten raw before breakfast (i) Eaten raw as salad, or cooked as vegetables. Brassica oleracea L. (Brassicaceae) Wild Cabbage AP (ii) A decoction is prepared from the plant leaves. 1 cup is taken daily for 4-5 months Brassica oleracea var. botrytis L. Caulifower FR (i) Eaten raw as salad (Brassicaceae) Camellia sinensis (L.) Kuntze Tea LE (i) A standard decoction is prepared from the plant. (Teaceae) Take 2 cups daily (i) Mix equal amounts of the leaves of senna, cumin, fennel, and anise leaves; eat one teaspoon daily afer Cassia senna L. (Fabaceae) Senna LE, SD lunch. (ii) A decoction is prepared from the leaves or the seeds; 1 cup is taken daily. (i) A decoction is prepared from the leaves. Take 3 cups daily. Cichorium pumilum Jacq. Dwarf Chicory AP (ii) Smash 5 teaspoons of the roots, mix with 1 L of (Asteraceae) water, and boil for 15 minutes. 1 cup is taken before meals Cinnamomum verum J. Presl Cinnamon Tree BRK (i) A standard decoction is prepared from the plant. (Lauraceae) Take 2 cups daily Citrullus lanatus (Tunb.) Matsum Watermelon FR (i) Eaten raw between meals & Nakai (Cucurbitaceae) (i) A juice is prepared from the fruit; one teaspoon is Citrus limon (L.) Burm. Fil Lime, Limon Tree FR taken daily before breakfast (Rutaceae) (ii) A standard decoction is prepared from the leaves. 1 cup is taken daily before breakfast. (i) Fruits are eaten raw or drunk as a juice 1- 2 cups Citrus paradisi Macfad. (Rutaceae) Grapefruit FR daily before breakfast Crataegus aronia (L.) Bosc. ex DC. Hawthorn LE (i) A decoction is prepared from the leaves. 1-3 cups are (Rosaceae) taken daily Cucumis sativus L. (Cucurbitaceae) Cucumber FR (i) Eaten raw between meal (i) Mix equal amounts of the seeds of cumin, fennel, anise, and senna leaves; eat one teaspoon daily afer lunch. Cuminum cyminum L. (Apiaceae) Cumin SD (ii) Soak the ground seeds overnight in boiled water and lemon. Drink the fltrate in the morning before breakfast for a month Cynara scolymus L. (Asteraceae) Artichoke FR (i) Fruits are eaten raw as salad (i) A decoction is prepared from the plant leaves and Eriobotrya japonica L. (Rosaceae) Medlar Tree LE olive leaves. Drink 1 cup twice a day. Eruca sativa Miller (Brassicaceae) Garden Rocket AP (i) Eaten raw with salad (i) Leaves are eaten with salad. Foeniculum vulgare Miller Fennel LE (ii) Seeds are boiled in water for 20 minutes; drink 2 (Apiaceae) cups daily for 3-4 weeks Lactuca sativa L. (Asteraceae ) Lettuce AP (i) Eaten fresh with salad. 4 Evidence-Based Complementary and Alternative Medicine

Table 1: Continued. Plant Derived Product (Family) English Common Name Plant Part Mode of Preparation (i) Seeds are soaked in water for few days and then eaten raw. Lupinus albus L. (Fabaceae) Lupine SD (ii) 1 teaspoon of the grinded seeds is taken daily. (iii) Te ground seeds are mixed with fenugreek seeds and honey; 1 teaspoon is taken daily. Malva sylvestris L. (Malvaceae) Common Mallow LE (i) Cooked as vegetables (i) Leave are soaked in hot water for 2 hours. Drink 1 Matricaria aurea (L.) Sch. Bip. Golden Cotula AP cup twice daily. (Asteraceae ) (ii) Add 3 teaspoons of the fowers to boiling water, fltrate, and have 1 cup twice a day for 1 month (i) A decoction is prepared from the plant. 1 cup is Mentha spicata L. (Lamiaceae) Peppermint AP taken when needed (i) A decoction is prepared from the plant leaves and Olea europaea L. (Oleaceae) Olive LE meddler tree leaves. Drink 1 cup twice a day. (i) A decoction is prepared from the plant; take 1 cup twice daily. Origanum syriacum L. (Lamiaceae) Wild Tyme, Mother of Tyme AP (ii) A decoction is prepared from plant mixed with Lion’s Foot, rosemary, and wild thyme. 1-2 cups are taken daily Paronychia argentea Lam. Silvery Whitlow- Wart AP (i) A decoction is prepared from plant mixed with lion’s (Caryophyllaceae) foot, rosemary, and wild thyme. 1-2 cups are taken daily (i) A standard decoction is prepared from the plant; Petroselinum sativum Hofm. Parsley AP take 1-3 cups/day. (Apiaceae) (ii) Eaten raw with salad (i) Mix equal amounts of the seeds of anise, cumin, Pimpinella anisum L. (Apiaceae) Anise SD fennel, and senna; eat one teaspoon daily afer lunch. Pistacia palaestina Boiss. Palestinian pistachio LE (i) A standard decoction is prepared from the plant; (Anacardiaceae) take 2 cups three time a day Portulaca oleracea L. Purslane SD (i) A standard decoction is prepared from the seeds; (Portulacaceae) take 1-2 cups daily (i)Tehuskisdried,ground,andthensoakedinwater. Punica granatum L. (Punicaceae) Pomegranate HS 1cupistakendaily. (i) Add one teaspoon of apple vinegar to a glass of Pyrus malus L. (Rosaceae) Apple FR water; drink 3 times daily afer meals. (ii) Drink 1 teaspoon of apple vinegar before breakfast. (i) A decoction is prepared from the plant; take 1 cup twice daily. Rosmarinus ofcinalis L. Rosemary AP (ii) A decoction is prepared from plant mixed with (Lamiaceae) Lion’s Foot, Silvery Whitlow-Wart, and wild thyme. 1-2 cups are taken daily (i) A standard decoction is prepared from the plant. Salvia fruticosa Mill. (Lamiaceae) Common Sage LE Take2-3cupsdailyforamonth. Teucrium capitatum L. (T. polium Cat Tyme LE (i) A standard decoction is prepared from the plant; L.) (Lamiaceae) take 1 cup/day when needed. (i) A decoction is prepared from 1 teaspoon of the seeds Trigonella berythea Boiss. & in 500 ml of water; take 1-2 cups daily. Blanche(T. foenum- graecum L.) Fenugreek SD (ii) Te ground seeds are mixed with fenugreek seeds (Fabaceae) and honey; 1 teaspoon is taken daily. Varthemia iphionoides Boiss & (i) A standard decoction is prepared from the plant. 1 Blanche (Chiliadenus Common Varthemia AP cup is taken twice a day iphionoides)(Asteraceae) Zingiber ofcinale Rose. Ginger Rz (i) A decoction is prepared from the rhizomes. 1 cup is (Zingiberaceae) taken daily ∗RZ: rhizome; HS: husk; AP: aerial parts; LE: leave; FR: fruits; SD: seeds; BRK: bark; FLE: feshy leaves; GLV: gloves. Evidence-Based Complementary and Alternative Medicine 5

15 min and centrifuged at 1500 g for 10 min and the clear where AS is the absorbance of the sample; AC is the supernatant was recovered. absorbance of the negative control (methanol without the sample). 2.2.2. Lipase Inhibition Reaction. Te ability of the plant Te IC50 value, which is defned as the concentration of extracts to inhibit PPL was measured using the modifed extract (mg mL-1) required to scavenge 50 % of DPPH, was method previously reported by Bustanji et al. [42]. Te calculated using the graph by plotting inhibition percentage lipase activity was determined by measuring the hydrolysis against serial extract concentration (1.0-0.016 mg/ml) [44]. of p-nitrophenol butyrate (pNPB) to p-nitrophenol at 410 Te antioxidant activity index (AAI) was calculated by nm using UV-VIS spectrophotometer. Lipase assays were dividing the DPPH fnal concentration (0.1 mg/ml) by the performed by incubating 200 �l of plant extract (5mg/ml IC50 of the plant extract [45]. ∘ ethanol) with 100 �lofPPLsolutionfor5minat37C; then 10�L of the pNPB substrate (100 mM in acetonitrile) was 2.3.2. Reducing Power Capacity Assessment. Te reducing added. Te volume was completed to 1 mL using the bufer. power (RP) was evaluated following the method of Oyaizu Te release of pNPB is estimated as the increment increase in [46]. In this technique, 1.0 ml of various concentrations of absorbance against blank. Te percentage of residual activity plants extracts (1.0-0.016 mg/ml) were mixed with 2.5 ml of of PL was determined by comparing the lipase activity in potassium bufer (0.2 M, pH 6.6) and 2.5 ml of potassium thepresenceandtheabsenceofthetestedinhibitors.Orlistat ferricyanide [K3Fe (CN) 6] (1 %) solution. Te mixture was ∘ (200 �g/ml) was used as a positive standard inhibitor control, incubatedfor30minat50C,andthen2.5mloftrichloro whereas plant extract was replaced by ethanol to be used as acetic acid (10 %) solution was added to the mix. Te total negative control. All experiments were repeated twice. mixture was centrifuged at 3000 g for 10 min. Ten 2.5 ml Inhibition of the lipase activity was expressed as the per- supernatantsolutionwaswithdrawnfromthemixtureand centage decrease in the activity when PPL was incubated with mixedwith2.5mlofdistilledwaterand0.5mlofFeCl3(0.1%) thetestcompounds.Lipaseinhibition(%)wascalculated solution. Blank sample was similarly prepared by replacing according to the following formula: extract with 60% ethanol, to calibrate the instrument (6800 (Δ −Δ ) UV-VIS spectrophotometer). Te absorbance of the solution = 100 × AControl ASample Lipase I% Δ wasmeasuredat700nm;higherabsorbanceindicateshigher AControl RP. BHT and ascorbic acid were used as standards. (1) Δ AControl= AControl− ABlank Te efective concentration at which the absorbance was 0.5 for reducing power (EC50) was obtained by interpolation Δ = − ASample ATest ABlank from linear regression analysis [47]. Increased absorbance of the mixture reaction indicates increasing RP [48]. 2.2.3. Minimum Inhibitory Concentration IC50. Te con- centration of most active plant extracts giving 50% lipase 2.4. Statistical Analysis. All results were expressed as mean ± inhibition (IC50) was performed using several concentrations standard deviation (n=3). Signifcance of diferences from the of the extracts, ranging from 0.156 to 5.0 mg/mL and the control was determined by Duncan’s test and a pvalue< 0.05 percentages of residual activity of PL data were used to was considered signifcant. evaluate the IC50 values. Te IC50 value of the extract was calculated from the least squares regression line of the semilogarithmic plot against percentage inhibition curve 3. Results using Microsof Excel version 10 sofware. All assays were repeated twice on diferent occasions, and the calculated Table 2 summarizes the results of antioxidant and antilipase inhibition percentages were the mean of 2 observations. inhibitory assays using ethanolic extracts from 78 medicinal plants (90 plants extracts) commonly administrated orally or topically to treat diverse diseases. 2.3. Antioxidant Capacity Assays Using the pancreatic lipase inhibition assay, the pancre- 2.3.1. DPPH (�, �-Diphenyl-�-picrylhydrazyl) Assay for Scav- atic lipase inhibition activity was determined by measuring enging Activity. DPPH radical scavenging activity was deter- the hydrolysis of pNPB to p-nitrophenol at 410 nm [42]. mined according to the method described by Choi et al. Te antioxidant activity was measured using the free-radical [43]. Briefy, 1 ml of the ethanolic plants extract (1mg/ml) or scavenging capacity (DPPH) and RP assays. Te RP was eval- standards (BHT and ascorbic acid) were mixed with 1.5 ml uated by measuring absorbance at 700 nm afer mixing the (0.02%)ofDPPHsolutioninmethanol.Temixturewas samples with ferric compounds; higher absorbance indicates incubatedinthedarkfor30min,andtheabsorbancewas higher RP. Te scavenging efects on DPPH radicals were measured at 517 nm in the spectrophotometer (6800 UV-VIS determined by measuring the decay in absorbance at 517 nm spectrophotometer) using methanol as blank. Te percentage due to the DPPH radical reduction, indicating the antioxidant of scavenging of DPPH radicals was calculated by using the activity of the compounds in a short time [49, 50]. following formula [27]: Pancreatic lipase inhibition was expressed in percentage (%) and IC50, whereas antioxidant activity was expressed �� ���V������ ���������� (%) = 100 − [( ) �100] (2) as AAI and EC50 using DPPH and RP capacity assessment �� techniques, respectively. 6 Evidence-Based Complementary and Alternative Medicine ± 0.2 ± 0.1 ± 0.3 ± 0.5 ± 0.2 ± 0.2 IC50 (mg/ml) ± 4.1± 0.6 1.31 ± 8.0± 0.4 0.76 ± 5.6 1.97 ± 0.9 ± 15.0± 0.2 1.17 ± 14.5 1.65 ± 14.8 1.28 ± 0.3 ± 22.2 1.92 M). Lipase inhibition (5mg/ml) % Inhibition ± 0.01 79.2 ± 0.01 94.9 Reducing Power ± 0.4 0.18 ± 0.1 84.0 ± 8.1 1.99± 0.8 ± 0.02 NA± 12.8 81.8 ± 0.5 2.32 ± 0.1± 0.1 2.33 0.13 ± 0.01 78.5 ± 0.9 2.56 ± 0.03 0.04 ± 0.0 95.3 ± 0.05 0.87 ± 0.03± 0.1 0.59 ± 0.8 97.4 ± 0.3 0.82 NA± 0.01 0.37 NA 72.7 NA 0.8 ± 0.03 NA± 2.6 74.9 1.45 NA 0.47 NA 0.46 ± 0.1 NA 96.8 ± 2.2 1.51 4.67 ± 0.1± 0.03 2.61 0.005 ± 0.0 95.1 ± 7. 6 1 . 24 Antioxidant capacity ± 0.10 0.23 ± 0.03± 0.06 0.52 ± 0.02 1.19 ± 10.8 82.2 2.46 ± 0.2 ± 0.01 ± 0.01 0.96 ± 0.1 1.87 ± 0.01 0.94 ± 0.00 1 ± 0.02 2.26 ± 0.1 0.11 ± 0.0± 1.5 99.0 0.45 DPPH IC50 (mg/ml) AAI ABS-700 nm EC50 (mg/ml) ± 7.7± 0.01 0.02 4.08 ± 4.1 0.10 ± 6.1 0.12 ± 0.01± 0.1 0.82 1.66 ± 0.02 0.41 ± 3.1 0.04 ± 0.00± 0.1 2.63 2.6 ± 0.1 0.05 ± 0.1 95.4 ± 1.2 NA ± 0.5 0.09 ± 0.02 1.11 ± 0.3 2.28 ± 0.08 0.16 ± 0.2 0.21 ± 0.03± 0.05 0.47 2.04 ± 0.03 0.15 ± 0.02± 2.0 92.5 ± 1.0 1.19 ± 0.9± 0.10 0.39 0.26 ± 3.30 0.05 ± 0.01 2.04 ± 0.4± 0.01 2.62 ± 0.0 0.03 ± 5.8 92.5 2 ± 0.2 ± 0.12 NA 85.3 (1mg/ml) % Inhibition Je’det Alsobian LE Laimoun 84.7 ± 2.10 0.43 LE Za’tar Farsi 88.0 ± 0.2 0.07 ± 0.01± 0.2 1.39 ± 0.02 2.43 ± 0.01 0.14 78.1 LE Zaizafon± 1.8 51.9 NA LE Summaq± 3. 95.1 0.02 AP Khubeizeh 21.3 AP Jarjeer 21.7 ± 0.5∗∗ NA AP Natesh 68.2 Plant part Arabic name Tea LE Shai 86.2 Tree Inula AP Irq tayyon 86.5 ± 0. 0.11 name Senna LE Sanamaki 31.2 Carob LE Kharrob 91.2 Jujube LE Inab 84.9 ± 0.2 0.10 Sumac Barnet Tyme Rocket Leaved Sicilian Garden Mallow Capitate Oleaster Shrubby Narrow- Turmeric RZ Kurkum 79.5 Common Common Rosemary AP Hasalban 89.9 Cat Tyme AP Peppermint AP Na’na’ 74.0 Lime, Limon Pomegranate HS Rumman 78.7 Table 2: Antioxidant and pancreatic lipase inhibition activity of Palestinian plants used in Traditional Arabic Palestinian Herbal Medicine (TAPH (L) (L.) L. L. L. L. L. L. Reichb. L.) L. (L.) Miller (L.) Spach. (L.) Camellia sinensis Cassia senna (Fabaceae) Punica granatum (Punicaceae) Citrus limon Burm. Fil (Rutaceae) Ziziphus sativa Gaertn. (Rhamnaceae) Malva sylvestris (Malvaceae) Eruca sativa (Brassicaceae) Sarcopoterium spinosum (Rosaceae) Rosmarinus ofcinalis L. (Lamiaceae) Elaeagnus angustifolia L. (Elaeagnaceae) Mentha spicata Rhus coriaria (Lamiaceae) (Anacardiaceae) Kuntze (Teaceae) (Zingiberaceae) Ceratonia siliqua Curcuma longa (Caesalpiniaceae) Scientifc name (Family) (Lamiaceae) Dittrichia viscosa Greuter (Asteraceae) Teucrium capitatumL. ( T. polium (Lamiaceae) Coridothymus capitatus Evidence-Based Complementary and Alternative Medicine 7 0.1 ± 0.1 ± 1.6 ± 0.8 ± 0.4 ± 0.1 ± 0.5 ± 0.2 ± 0.0 IC50 (mg/ml) ± 1.7 2.68 ± 0.2 ± 5.2 3.01 ± 8.5 3.01 ± 4.8 2.77 ± 0.6 ± 9.7 2.88 ± ± 6.9 3.11 ± 0.1 ± 19.1 3.36 Lipase inhibition (5mg/ml) % Inhibition ± 071.2 ± 0.1± 2.1 65.8 3.45 ± 0.02± 8.9 72.7 ± 0.04 2.73 ± 0.02 0.46± 0.00± 11.8 72.9 ± 0.3 3.21 ± 0.2 1.68 ± 0.03± 0.03 0.39 ± 8.3 69.1 ± 0.2 2.81 ± 0.1 2.29 ± 0.02 0.12 ± 0.02± 2.8 55.4 3.47 NA 0.46 ± 0.01 NA 72.9 NA± 0.01 0.43 Na 77.4 NA 0.13 ± 0.01 NA 73.5 NA± 0.03 0.17 NA± 2.4 75.7 3.16 Antioxidant capacity ± 0.06 1.23 ± 1.5 2.66 ± 0.01 0.05 ± 0.02± 0.2 0.82 ± 0.13 1.51 0.4 ± 0.02 70.1 ± 0.08 0.25 ± 0.03 1.28 ± 0.01± 0.01 0.33 72.2 ± 0.04 0.71 ± 0.06 0.2 ± 0.1± 0.03 0.73 0.71 NA DPPH Reducing Power IC50 (mg/ml) AAI ABS-700 nm EC50 (mg/ml) Table 2: Continued. ± 1.4 0.60 ± 0.02± 0.01 0.17 1.42 ± 0.11± 0.03 0.35 68.7 ± 6.2 3.3 ± 0.4 ± 0.5 NA ± 0.2 0.09± 0.01 1.11 ± 0.7± 0.03 0.37 0.27 ± 0.1± 0.02 0.74 ± 0.01 0.69 83.2 ± 0.6 0.13 ± 0.00± 0.02 0.76 ± 00.32 1.51 ± 0.31 0.51 ± 1.60 0.6 ± 0.07± 0.03 0.17 0.79 ± 0.01 0.7 ± 0.02 71.3 ± 10.2 2.94 ± 0.2 ± 3.20 0.08 ± 0.23 NA ± 0.51 NA 89.0 (1mg/ml) 19.0 % Inhibition Kharrob Kaf Alasad Rijl Alasad, LE Seder 86.2 ± 2.6 0.12 LE Hindba’ 82.7 LE LE Lufe± 0.58 83.8 ± 0.03 0.49 0.2 ± 0.0 0.67 ± 0.01 0.77 ± 0.00± 9.2 76.5 ± 0.8 2.88 AP Za’tar± 2.8 82.9 0.34 ± 0.29 0.29 ± 0.4± 0.09 1.93 0.18 ± 0.01 60.9 ± 9.5 3.31 AP Maryemeyeh 91.0 Plant part Arabic name Sage name Arum Carob SD ummer Dwarf Guava LE Guava 69.6 Fennel LE Shoumer 74.9 Savory Cumin SD Kamoon 45.0 Mantle Walnut LE Jouz± 3.22 82.2 0.14 Christ’s Lady’s – Chicory S Purslane SD Baqleh 88.9 ± 0.71 0.41 Purslane AP Baqleh± 0.9 82.9 ± 0.07 0.53 ± 0.01 0.19 1.21 Common Common Artichoke FR Kharshouf 3.8 Artichoke FR Kharshouf 8.1 Hawthorn LE Za’rour Sha’ek 85.0 white sage, Palestinian Lion’s Foot, Kermes Oak LE Sendian 76.1 Sage, Garden Torn Jujube L. L. L. L. L. L. L. Mill. Rothm. L. chorium pumilum Foeniculum vulgare Miller (Apiaceae ) Ziziphus spina-christi (L.) Desf. (Rhamnaceae) Jacq. (Asteraceae) Cuminum cyminum (Apiaceae ) (Lamiaceae) Ceratonia siliqua L. (Caesalpiniaceae) Alchemilla xanthochlora ( Alchemilla vulgaris auct.) (Rosaceae) Salvia fruticosa Psidium guajava (Myrtaceae) Scientifc name (Family) Cynara scolymus (Asteraceae) Cynara scolymus (Asteraceae) Portulaca oleracea (Portulacaceae) Crataegus aronia (L.) Bosc. ex DC. (Rosaceae) Quercus calliprinos Webb (Fagaceae) Satureja thymbra Portulaca oleracea (Portulacaceae) Juglans regia (Juglandaceae) Arum palaestinum Boiss. (Araceae) (Lamiaceae) Ci 8 Evidence-Based Complementary and Alternative Medicine IC50 (mg/ml) 2.7 NA ± 5.4 NA ± 5.3 3.67 ± 0.1 ± 4.5 NA ± 2.0 NA ± 5.6 NA ± 0.9 NA Lipase inhibition 63.8 (5mg/ml) % Inhibition ± 0.02 0.88 ± 0.09± 7. 49.5 9 NA ± 0.0± 0.04 0.63 1.06 ± 0.12 35.4 ± 0.4± 0.02 2.37 0.15 ± 0.01 44.3 ± 0.0 0.22 ± 0.01 NA± 0.03 0.19 NANA 38.4 ± 3.2 0.48 ± 0.06 NA NA± 6.1 32.5 NA 0.44 ± 0.3 2.06± 0.02 0.26 ± 0.02 46.1 Antioxidant capacity ± 0.12 ± 0.04 0.1 DPPH Reducing Power IC50 (mg/ml) AAI ABS-700 nm EC50 (mg/ml) Table 2: Continued. ± 4 0.09 ± 0.03 1.11 ± 7. 6 1 . 02 ± 1.8 0.3 ± 0.08± 0.1 0.33 ± 0.03 1.02 0.57 ± 0.02± 1.6 41.5 NA ± 4.7± 0.08 0.33 0.3 ± 0.1± 0.02 0.85 ± 0.02 0.59 ± 2.8 45.8 NA ± 0.3 0.29 ± 0.00 0.34 ± 0.0 0.71 ± 0.1 0.23 ± 4.0 0.47 ± 0.01 0.21 46.5 ± 7.7 NA ± 0.778.7 0.38± 0.02 0.26 ± 0.1 1.05 ± 0.01± 0.01 0.43 68.4 ± 17.1 4.23 ± 1.1 80.2 ± 2.3 0.15 ± 0.01± 0.04 0.65 2.46 ± 0.06 0.09± 0.01 37.1 (1mg/ml) % Inhibition Rijl halabi Kabsh Koronful Sonawabar Alhamameh LE Kappar 90.47 ± 4.0± 0.15 0.24 0.42 ± 0.3 1.09± 0.02± 0.07 0.52 ± 7. 49.0 7 NA LE Kina 87.9 SD Hilbeh 60.2 SD Qezha 34.4 ± 9.0 NA AP AP Mardaqoush 82.1 AP Babounej± 14.6 75.1 ± 0.06 0.39 0.26 ± 0.04± 0.02 0.82 ± 0.09 0.69 38.5 ± AP Za’tar bari 81.4 BRK Qerfeh 86.4 ± 1.9 0.06 ± 0.02 1.54 ± 0.4 2 ± 0.18± 0.02 0.24 40.5 ± 8.6 NA Plant part Arabic name Tree Seed Wart Gum Olive LE Zaitoun 91.1 ± 2.5± 0.02 0.29 ± 0.02 0.35 ± 0.05 1.02 0.54± 0.04 36.8 ± 1.3 NA name Clove FLW Anise SD Yansoon 83.3 Caper Sweet- Cotula Silvery Spurge AP Halabloub 90.5 Tyme Cumin Golden Fig Tree LE Teen 82.2 Egyptian Whitlow- Common Red River Mother of Marjoram Fenugreek Cinnamon Nightshade AP Samweh± 4.0 83.0 0.44 ± 0.02 0.23 ± 0.01± 0.13 0.78 0.8 ± 046.3 Caper Bush, Aleppo Pine AP Wild Tyme, Nigella, Black L. L. L.) T. (L.) L. L. Mill. Boiss. L. Dehn. sDC. L. Blume. gella ciliari Olea europaea (Oleaceae) Pimpinella anisum (Apiaceae ) Scientifc name (Family) Trigonella berytheaBoiss. & Blanche( foenum- graecum (Fabaceae) Paronychia argentea Lam. (Caryophyllaceae) Capparis spinosa (Capparaceae) (Solanaceae) Solanum nigrum Origanum majorana L. (Lamiaceae) (Ranunculaceae) Syzygium aromaticum (L.) Merr. and Perry. (Myrtaceae) Pinus halepensis (Pinaceae) Euphorbia hierosolymitana (Euphorbiaceae) Eucalyptus camaldulensis (Myrtaceae) Origanum syriacum (Lamiaceae) Matricaria aurea Sch. Bip. (Asteraceae) Ficus carica (Moraceae) Ni Cinnamomum zeylanicum (Lauraceae) Evidence-Based Complementary and Alternative Medicine 9 IC50 (mg/ml) ± 2.3 NA ± 3.9 NA ± 7. 6 NA ± 3.2 NA ± 0.2 NA ± 2.6 NA ± 6.8 NA ± 2.3 NA ± 2.5 NA Lipase inhibition (5mg/ml) % Inhibition NA 17.1 Reducing Power ± 0.01 0.4 ± 0.03 20.6 ± 5.4 NA 0.28± 0.1 0.35 ± 0.03± 0.21 0.65 0.94 ± 0.06 22.9± 2.6 NA ± 0.02 0.18 ± 0.01 NA 16.1 NA 0.46± 0.18 NA 23.4 NANA± 0.13 0.43 NA 0.06 ± 0.01 NA 0.28 ± 0.17 NA± 19.6 19.9 NA 19.9 NA ± 2.5 17.5 NA Antioxidant capacity ± 0.35 0.1 NA DPPH ± 0.010.17 ± 0.02 0.59 ± 0.24 1.92 0.25± 0.02 30.2 ± 0.1 NA IC50 (mg/ml) AAI ABS-700 nm EC50 (mg/ml) Table 2: Continued. ± 7.8 0.77 ± 0.00 0.13 ± 0.0± 0.01 0.45 NA 16.7 ± 2.2 ± 0.9 0.40 ± 0.01 0.2 ± 0.0 1.12 ± 4.9 0.4 ± 0.06 0.23 ± 0.03 0.48 ± 0.16 NA 28.6 ± 0.5 0.50 ± 0.01 0.2 ± 0.0± 0.05 0.73 ± 0.07 0.82 22.5 ± 4.1 NA ± 0.7 0.60 ± 0.08 0.18 ± 6.0± 0.04 0.74 0.13 ± 0.01± 0.24 0.53 1.6 ± 0.61± 2.8 32.3 NA ± 0.2 NA ± 0.6 0.45 ± 0.00 0.22 ± 0.0± 0.22 0.75 0.87 ± 0.08± 1.2 16.5 NA ± 0.6 NA ± 14.3 1.47 ± 1.189.98 ± 0.02 0.17 0.57 ± 0.1± 0.12 1.37 ± 029.0 0.32 (1mg/ml) % Inhibition Botom Falastini LE LELE Pasifora Habaq 79.2 ± 0.5 81.1 LE Ghar 85.9 FR Kappar 20.1 SD Summaq 30.2 AP Retem 70.4 AP Kteileh 84.6 EPC Summaq± 1.3 92.8 ± 0.01 0.02 ± 1.32 4.37 2.66± 0.06 0.06 ± 025.5 Plant part Arabic name Bay Rue AP Figan± 0.4 73.8 0.34 ± 0.24 0.29 ± name Caper Carob FR Kharrob 27.0 fower Sumac Sumac Myrtle Fennel SD Shoumer 87.0 Ginger RZ Zanjabeel 79.0 Lupine SD Tormous Mor 16.2 Sicilian Sicilian Passion Retama, Egyptian pistachio, Mulberry FR Toot 69.4 Common Common Common Terebinth Varthemia Palestinian Caper Bush, Laurel, Sweet White Broom L. L. Cress SD Rashad 92.2 L. L. L. ) ) L. L. L. L. ) Morus nigra (Moraceae) Foeniculum vulgare Miller (Apiaceae ) Retama raetam (Forssk.) Webb (Fabaceae) Rhus coriaria Rhus coriaria (Anacardiaceae) ( Anacardiaceae Myrtus communis (Myrtaceae) Pistacia palaestina Boiss. (Anacardiaceae) Scientifc name (Family) Passifora incarnata (Passiforaceae) Ceratonia siliqua L. (Caesalpiniaceae Lepidium sativum Zingiber ofcinale Rose. (Zingiberaceae) Capparis spinosa (Capparaceae) Varthemia iphionoides Boiss & Blanche ( Chiliadenus iphionoides (Asteraceae) Lupinus albus L.(Fabaceae) Ruta chalepensis (Rutaceae) Laurus nobilis (Lauraceae) 10 Evidence-Based Complementary and Alternative Medicine IC50 (mg/ml) ± 1.0 NA ± 2.7 NA ± 0.7 NA ± 2.4 NA ± 2.8 NA ± 7. 4 NA ± 0..0 NA 5 . Lipase inhibition ± 0.47.4 NA 11.2 ± 1.1 NA 11.2 ± 1.1 NA (5mg/ml) % Inhibition A9 Reducing Power ± 0.04 NA 0.11 ± 0N NA 0.22 ± 0.05 NA NA 0.22 ± 0.05 NA NA± 0.04 0.32 NANA 13.7 ± 1.1 0.04 ± 0.00 NA NA 11.6 ± 0.5 NA NANA 0.07 ± 0.00NA± 0.01 0.19 NA 0.12 ± 0.01 NA 13.5 ± 2.0 NA 12.4 NA 12.4 NA± 0.01 0.17 NA 15.7 NA 0.13 ± 0.01 NA 10.1 NA 0.18 NA NA 0.18 ± 0.03 NA± 0.9 10.1 NA Antioxidant capacity NA NA NA DPPH IC50 (mg/ml) AAI ABS-700 nm EC50 (mg/ml) Table 2: Continued. ± 6 ± 1.2 0.26 ± 0.02 0.4 ± 0.03 1.5 ± 0.02± 0.01 0.33 15.2 ± 7.1± 0.11 0.33 0.3 ± 0.1± 0.23 0.75 ± 0.02 0.58 ± 11.5 14.3 NA ± 0.2 NA ± 2.7 NA ± 5.6 0.6 ± 0.02 0.16 ± 0.01 0.42 ± 0.16 NA± 2.2 9.7 NA ± 0.3 NA ± 3.2 NA ± 0.8 NA ± 0.8 ± 12.0 NA ± 0.0 ± 0.32 NA 31.9 (1mg/ml) % Inhibition Sabrah murrah FR Zaizafon 8.6 ± 0.8 NA SD Fasolia’ 25.0 RT Hindba’ 4.9 ± 0.2 NA Plant part Arabic name Aloe LE Bean name Dwarf Leaved Parsley AP Baqdounes 27.7 Lettuce AP Khass 28.6 Sesame SD Semsem 11.0 Cypress LE Saro 91.48 Chicory Oleaster Narrow- Common Common Coriander SD Kozbareh 85.9 Cucumber FR Khiar 1.0 Blackberry LE Oliq 88.1 ± 4.6 0.4 ± 0.16± 0.1 0.24 ± 0.01 0.49 NA 10.1 Caulifower FR Qernabeet 2.0 Caulifower FR Qernabeet 2.0 Tree Of Life LE Afs 82.0 Watermelon FR Bateekh 2.8 Pomegranate SD Rumman 42.9 L. L. L. L. L. L. Schreb. ea var. L. (L.) Burm. f. L. L. Phaseolus vulgaris (Fabaceae) Cucumis sativus Petroselinum sativum Hofm. (Apiaceae ) Brassica olerac (Cucurbitaceae) botrytis (Brassicaceae) Punica granatum (Punicaceae) Brassica oleracea var. botrytis (Brassicaceae) Aloe vera (Xanthorrhoeaceae) Scientifc name (Family) Elaeagnus angustifolia L. (Elaeagnaceae) (Cupressaceae) Cupressus sempervirens Tuja occidentalis (Cupressaceae) Citrullus lanatus (Tunb.) Matsum & Nakai (Cucurbitaceae) Cichorium pumilum Jacq. (Asteraceae) Coriandrum sativum L. (Apiaceae ) Sesamum indicum (Pedaliaceae) (Asteraceae) Lactuca sativa (Rosaceae) Rubus sanctus Evidence-Based Complementary and Alternative Medicine 11 IC50 (mg/ml) Lipase inhibition 2.3 ± 1.2 NA 2.5 ± 1.6 NA 1.7 ± 2.4 NA 0.1 ± 0.0 (5mg/ml) % Inhibition ± 0.2 92 ∗∗ NA: not applicable. es. ± 0.01 NA 4.4 ± 0.2 NA ± 0.02 NA ± 0.07 NA ± 0.04 NA 2.0 ± 0.2 NA NA 0.27 ± 0.06 NA 6.3 ± 5.4 NA NA 0.1 NA 0.1 NANA 0.1 0.1 Antioxidant capacity NA DPPH Reducing Power IC50 (mg/ml) AAI ABS-700 nm EC50 (mg/ml) Table 2: Continued. ± 7.6 NA ± 5.1 0.5 ± 0.05± 0.02 0.19 ± 0.07 0.62 0.98 ± 0.1 6.3 ± 0.4 NA ± 0.1 0.5 ± 0.0 0.2 ± 0.00 1.1 ± 0.08 0.34 ± 0.1 2.0 ± 1.6 NA ± 0.9 3.6 ± 1.9± 0.02 0.03 0.4 ± 0.06 NA ± 5.2 2.5 ± 0.3 NA (1mg/ml) % Inhibition ± 0± 0.0 0.03 3.9 ± 0.01 1.5 ± 0.08 0.06 ± 0.02 ± 0.57± 0.0 0.03 3.2 ± 0.51 0.8 ± 0.05 0.06± 0.00 89.2 Aljeneh Laimoon 93.4 AP Malfouf 40.0 ± 10.9 NA Plant part Arabic name Wild name Apple FR Tufah 26.1 GrapeGarlic FR GLV Inab Toum 87.5 3.1 Roselle FLW Karkadaih 89.1 Onions FLE Basal± 8.1 18.0 NA Cabbage Common Grapefruit FR Limon Tree FR Laimoun 52.5 L. L. L . L. (L.) L. L. BHT (100ug/ml) Hibiscus sabdarifa (Malvaceae) Scientifc name (Family) Brassica oleracea (Brassicaceae) Ascorbic acid (100ug/ml) (Rosaceae) Vitis vinifera (Vitaceae) Allium sativum (Amaryllidaceae) Pyrus malus Citrus paradisi Macfad. (Rutaceae) Allium cepa Citrus limon Burm. Fil (Rutaceae) (Amaryllidaceae) Orlistat (200 ug/ml) ∗ RZ: rhizome; HS: husk; AP: aerial parts; LE: leave; FR: fruits; SD: seeds; BRK: bark; FLW: fowers; EPC: epicarp; RT: roots; FLE: feshy leaves; GLV: glov 12 Evidence-Based Complementary and Alternative Medicine

Seeds, 14 Te RP was measured by direct electron donation in Aerial parts, 3+ − 6 2+ − 6 23 the reduction of Fe (CN ) –Fe (CN ) .Teproductwas visualized by forming the intense Prussian blue color complex Roots, 1 and then the absorbance was measured at the 700 nm; Rhizome, 2 a higher absorbance value indicates a stronger RP of the samples. Bark, 1 Using ferric reducing power assay, the EC50 value for the ethanolic extracts ranged between 1.6 and 0.005 mg/ml. Epicarp , 1 Te EC50 of the leaves of Rhus coriaria, fruit husk of Punica Leaves , 31 Flowers , 2 granatum,arealpartsofSarcopoterium spinosum,leavesof Quercus calliprinos,leavesofCeratonia siliqua,andepicarp of Rhus coriaria were 0.005, 0.03, 0.04, 0.05, and 0.06 Fruits, 12 mg/ml, respectively, whereas the EC50 value for the positive Glove, 1 controls ascorbic acid and BHT was 0.057 mg/ml for both Fruit Husk , 1 controls (Figure 3, Table 2). Tese results indicate the rela- Figure 1: Plant parts used in the study. tivelyhighferricreducingactivityofthesemedicinalplant extracts compared to the pure standards ascorbic acid and BHT. 100.0 90.0 3.2. Pancreatic Lipase Enzyme Inhibition Activity. Ninety 80.0 crude extracts were prepared from natural plant species, 70.0 either collected from the Nablus area or purchased from 60.0 traditional drug shops, and their antilipase activity was 50.0 investigated at a concentration of 5 mg/mL for PPL inhibition. 40.0 A variety of the tested plant extracts shows a strong inhibitory 30.0 potential to the pancreatic lipase digestive enzyme (Table 2); 20.0 the PPL inhibitory activity of the tested plant extracts ranged 10.0 DPPH percentage of inhibition percentage of DPPH 0.0 between 1.7 and 98.97 %. Te plant extracts were divided 0.00 0.02 0.04 0.06 0.08 0.10 0.12 0.14 into three categories, which were low (< 30%) inhibition, Concentration (mg/ml) medium (30-70%) inhibition, and high (> 70%) inhibition ∘ when incubated with PPL for 10 min at 37 C. Te PPL Punica granatum Rhus coriaria (epicarp) inhibition assay screening detected 29 extracts exhibiting Sarcopoterium spinosum Rhus coriaria (leaves) > Ceratonia siliqua high ( 70%) inhibition while 23 extracts with medium (30- 70%) inhibition and the remaining 38 plant extracts showed Figure 2: Antioxidant activity of the fve most active plants’ low inhibition (< 30%). All plants extracts were set at 5 mg/ml ethanolic extract using DPPH. Experiments have been performed as this concentration could give a consistent result with low in triplicate. standarddeviationintheassay. Te signifcant inhibition of PPL was observed up to 99.0 % with Camellia sinensis leaves, 97.4% with Curcuma Of the 90 ethanolic crude extracts, 31 were prepared from longa rhizomes, and 96.8 of Elaeagnus angustifolia leaves. leaves, 23 from aerial parts, 14 from seeds, 12 from fruits, two Treatment with orlistat (at fnal concentration 200 �g/mL) from each rhizomes, fruit husk, and fowers, and one from as a positive control, a well-known antilipase agent, signif- the epicarp, root, gloves, and bark (Figure 1). Te selection of icantly inhibited the PPL activity up to 92.0 %. Orlistat, a plants part was primarily dependent on the signifcant role in hydrogenated derivative of lipstatin, is the only pancreatic traditional medication or cooking purposes [41, 51]. lipase inhibitor currently approved for a long-term treatment of obesity. 3.1. Antioxidant Activity. Antioxidant activity of plant Among the 90 plant extracts examined, 37 (41 %) crude extracts using the DPPH assay ranged between 1.0 and 95.1% extracts from natural plant species showed antilipase activity for plant extracts at a concentration of 1 mg/ml. Sixty-one of more than 50%. Tese were further investigated for their extracts exhibited antioxidant activity ≥ 50 %. Te IC50 PPL inhibitory efects at diferent concentrations, and a dose- values for the leaves and epicarp of Rhus coriaria,aerialparts response curve was obtained. Figure 4 presents the top 5 plant of Sarcopoterium spinosum,leavesofCeratonia siliqua,and extractsincomparisonwithorlistatasacontrol.Temost the fruit husk of Punica granatum were 0.02, 0.02, 0.02, 0.04, active plants by means of IC50 value were Camellia sinen- and 0.05 mg/ml (Figure 2), respectively. Twenty-one plant sis (0.45 mg/ml), Ceratonia siliqua (leaves) (0.76 mg/mL), extracts exhibited AAI > 0.5; the antioxidant activity indices Curcuma longa (0.82 mg/mL), Sarcopoterium spinosum (1.17 (AAIs) for Rhus coriaria leaves and epicarp, Sarcopoterium mg/mL), and Mentha spicata (1.19 mg/mL). spinosum,andCeratonia siliqua were higher or comparable Of the 41 plant extracts used by Palestinian in TAPHM for to the AAI of ascorbic acid (3.85) (Table 2). Tis indicates the the treatment of obesity 16 plant extracts (39%) have shown high potential for free-radical scavenging of these extracts. possessing a strong PPL inhibitory activity > 70%, 7 with Evidence-Based Complementary and Alternative Medicine 13

3.00

2.50

2.00

1.50

ABS (700 nm) 1.00

0.50

0.00 0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.80 0.90 1.00 Concentration (mg/ml)

Quercus calliprinos Rhus coriaria (epicarp) Punica granatum Rhus coriaria (leaves) Sarcopoterium spinosum Syzygium aromaticum Ceratonia siliqua

Figure 3: Antioxidant activity of the seven most active plants extracts using reductive potential. Experiments have been performed in triplicate.

Curcuma longa Ceratonia siliqua (leaves) 100% 100%

80% 80%

60% 60%

40% 40%

20% 20% Percentage of inhibition of Percentage Percentage of inhibition of Percentage 0% 0% 012345 012345 Concentration (mg/ml) Concentration (mg/ml) Mentha spicata Sarcopoterium spinosum 100% 100%

80% 80%

60% 60%

40% 40%

20% 20% Percentage of inhibition of Percentage Percentage of inhibition of Percentage 0% 0% 012345 012345 Concentration (mg/ml) Concentration (mg/ml) Camellia sinensis 100% 100% Orlistat 80% 80%

60% 60%

40% 40%

20% 20% Percentage of inhibition of Percentage 0% inhibition of Percentage 0% 012345 0 0.05 0.1 0.15 0.2 0.25 Concentration (mg/ml) Concentration (mg/ml)

Figure4:Porcinepancreaticlipaseinhibitory(PPLI)activityofCamellia sinensis, Ceratonia siliqua, Curcuma longa, Sarcopoterium spinosum, and Mentha spicata. Orlistat was used as a positive control. Experiments have been performed in triplicate. 14 Evidence-Based Complementary and Alternative Medicine medium PPL inhibitory activity, while the rest (18) exhibited appetite[59].However,pancreaticlipaseinhibitoryefectis weak activity < 30 % (Table 2). one of the most widely studied mechanisms to determine the potential activity of natural products as obesity modulating 4. Discussion agents [60]. Several studies have been conducted to evaluate the pan- With more people avoiding chemical drugs for the manage- creatic lipase inhibitory activity of plant extracts; these studies ment of overweight and obesity, due to the fear of health have led to the identifcation of several plants and the isola- adverse side efects, tendency is now towards natural-based tion of natural compounds with PPL inhibitory activity [15, products; thus the development of new antiobesity molecules 27]. In our study, the most active PPLI plant extracts by means from natural products has become a necessity. Tis seems of minimum inhibitory concentration (IC50)wereCamellia doable because, in traditional herbal medicine, several plants sinensis, Ceratonia siliqua, Curcuma longa, Sarcopoterium are used for their weight- reducing efects. Te plant bioactive spinosum, Mentha spicata, Rhus coriaria L. (Anacardiaceae), constituents are expected to act as natural inhibitors of Dittrichia viscosa (L.) Greuter (Asteraceae), Rosmarinus ofc- digestive lipases [22, 52]. Antioxidant and in vitro porcine inalis L. (Lamiaceae), Eruca sativa Miller (Brassicaceae), and pancreatic lipase, PPL, inhibitory tests were conducted on Elaeagnus angustifolia L. (Elaeagnaceae) (Table 2). seventy-six plants, of which thirty-nine species with weight- In the following, we discuss some of these plants and their reducing or related potential were used in Palestinian tradi- possible action mechanisms. tional medicine, to fnd new crude antiobesity products from Camellia sinensis (tea) was among the most active plant natural sources. extractsasPPLIinthisstudybymeansofIC50.Ourresults In this study 59.3 % and 68.6 % of the plants extracts are in accordance with those of other researches which have shown possessing antioxidant activity using the RP and demonstrated that a tea-based drug (Exolise) standardized DPPH assays, respectively. Te percentages of DPPH free- with the active component catechin at 25% was proposed as radical scavenging activity and ferric reducing power were a natural antiobesity agent, showing strong PPLI activity and foundtobemaximumat1mg/mLoftheplantextract.Te increase in thermogenesis [61]. antioxidant activity of the plant extracts has shown being A randomized, double-blind, placebo-controlled clinical comparable using the DPPH and the RP assays (Table 2); trial was conducted to explore the efect of the consumption both assays revealed similar antioxidant activity of the tested of high-dose of green tea extract on weight reduction [62]. extracts except for a very small number of extracts (5 extracts, Te study revealed a signifcant weight loss, reduced waist 5.5 %). Te leaves and epicarp of Rhus coriaria exhibited the circumference, and a consistent decrease in total cholesterol highest antioxidant activity in both assays. However, only 5 and LDL plasma levels without any side or adverse efects plant extracts, Rubus sanctus, Coriandrum sativum, Zingiber in women with central obesity [62]. Diferent types of tea ofcinale, Ruta chalepensis,andRetama raetam,haveshown areamongthemostwidelyinvestigatednaturalmaterials possessing strong scavenging capacity by DPPH, while they for pancreatic lipase inhibition. Various polyphenols (e.g., exhibited low RP activity. Both DPPH and RP are known L-epicatechin, epicatechin gallate (ECG), epigallocatechin to be related to the nature of polyphenolics contributing to (EGC), and epigallocatechin gallate, EGCG) isolated from tea their electron transfer/hydrogen donating ability [53]. Tus, leaves showed strong inhibitory activity against pancreatic it is preferred to assess the antioxidant capacity of a plant lipase [63]. Te efcacy of tea polyphenols (e.g., catechins: extract by more than one method, as diferent methods epigallocatechin gallate, EGCG) in regulating multiple targets can assess scavenging capacity of diferent free radicals and concludes in inhibiting pancreatic lipase activity, reducing this can explain the diference in the antioxidant activity of nutrient absorption, impairing adipogenesis, suppressing the tested plant extracts using DPPH and RP assays. Free appetite, enhancing cellular oxidation defenses, activating radicals are involved in many disorders like cancer, diabetes AMP-activated protein kinase in the skeletal muscle, adipose mellitus, and neurodegenerative and infammatory diseases. tissues, and liver, and improving systemic infammation, Antioxidants due to their scavenging activity are useful for hyperglycemia, and insulin resistance [56–59]. Trough the management of those diseases [54, 55]. these diverse mechanisms tea catechins reduce obesity and Allplantsanalyzedinthisstudyhavebeenreportedin decrease the adverse health efects of obesity and related com- TAPHM to be used for the treatment of one or more ailments plications [59, 61]. including chronic diseases [40]. However, 39 of these plants Carob (Ceratonia siliqua)isalargeleguminoustreeofthe which possess high antioxidant activity (> 50%) by either Mediterranean area, belonging to the Caesalpiniaceae family. method, DPPH or RP, have been reported by the Palestinian Te plant is used in TAPHM for the treatment of abdominal people to be used as food, either tea (53.8 %), raw (43.6%), or pain, diarrhea, stomach ulcer, diabetes, chest pain, cough, and seasoning (41.0 %). Tis would indicate the safety of using urinary tract infections [40, 41]. Carob is utilized mainly for these plants as natural antioxidant agents for therapeutical the industrial conversion of the seeds, to obtain locust bean uses. gum or carob gum and germ four as a by-product, which Five basic mechanisms have been suggested for the are used in food preparations as a thickening agent and a weight-reducing efects of antiobesity natural products source of protein, respectively [64]. Te locust bean gum has including inhibiting pancreatic lipase activity [56], promot- been shown to possess lipid-lowering efects and to inhibit ing lipolysis [57], preventing adipogenesis [58], promoting acylated ghrelin, the hunger hormone. Tis hormone has thermogenesis and lipid metabolism [58], and controlling efectonmakingsubjectsmoresatiatedatmealsandmaking Evidence-Based Complementary and Alternative Medicine 15 satiation last a long time, decreasing postprandial responses treatment of several ailments including fatulence, intestinal of triglycerides and nonesterifed fatty acids, and altering worms, hepatitis, atherosclerosis, and skin wounds and burns respiratory amount, suggesting a change towards enhanced [41]. fatty acid oxidation [65, 66]. In the present study, the plant rhizomes exhibited strong In this study the leaves, pods, and seeds of carob were PPLI activity (97.4 %, IC50 0.8 mg/mL). Tis is in agreement analyzed for their PPLI activity; the leaves and seeds of the with those of Yadav and Chaudhurym [76] and Witkin and plant have shown possessing strong PPLI activity with IC50 Li[77]whoalsoreportedasignifcantantiobesityactivityof of0.8and3.3mg/mL,respectively.Tiscanbeattributed the plant. Curcumin is the main constituent of the plant; it tothefactthatcarobproductshavebeenfoundtocontain promotes weight loss and reduces the incidence of obesity- an array of bioactive compounds including polyphenols and related diseases by inhibiting preadipocyte diferentiation, favonoids that possess antiobesity properties [67]. On the inhibiting macrophage expansion and infltration in white other hand, the seeds of the plant have been shown to adipose tissue, suppressing infammatory adipokine secre- contain various bioactive favonoid compounds including tion from white adipose tissue, and promoting cytoprotective epicatechin, epicatechin gallate, and myricetin with higher antioxidant expression [78]. concentrations than in pods [67, 68]. Mentha spicata (spearmint) is belonging to the Lamiaceae A study performed by Vaya & Mahmood [69] has shown family. Its extracts (juice and leaf oil) are known to possess that carob leaves contain nine diferent favonoids, with several pharmacologic activities, including antioxidant [79], myricetin as the major constituent. Interestingly, Su et al. [70] antimicrobial [80], antitumor [81], anti-infammatory [82], showed that consumption of myricetin may help to prevent and diuretic [83] properties. It is commonly used in TAPHM obesity and obesity-related metabolic complications. Tey in the form of tea as a home remedy to help alleviate stomach found myricetin treatment to efectively decrease the size pain, to stimulate digestion, notably of fats, and to treat and number of epididymal adipocytes and hepatocytes and obesity, muscle spasm, headache, menstrual pain, and other reduce fat mass compared with the high-fat diet- (HFD-) digestive system ailments [41]. Mint was among the 39 plants induced obesity in mice without myricetin. It was suggested reported in TAPHM to be utilized for weight loss. Te PPLI that that myricetin may suppress the expression of adipogenic results of the mint extract in this study are in accordance and lipogenic genes, thereby regulating the onset of obesity with its traditional use in Palestine and other countries for [71, 72]. the treatment of obesity [41]. In vivo studies on the efects of polyphenol-rich infusion Te M. spicata extract contains several bioactive ingre- from carob leaves on infammation associated with obesity dients with known antiobesity properties and is potentially and dextran sulfate sodium- (DSS-) induced ulcerative colitis useful in treatment of obesity and overweight related com- in Swiss mice showed that carob leaf infusion decreased plications (e.g., diabetes and cardiovascular diseases). Tese infammation severity linked with HFD-induced obesity and compounds include favonoids such as catechin, epicatechin, dextran sulfate sodium- (DSS-) induced acute colitis desig- rutin, myricetin, luteolin, apigenin, naringenin, kaempferol, nated by reduction in proinfammatory cytokines expression and quercetin and phenolic acids such as rosmarinic, gallic, in adipose tissue, colon, and spleen [73]. Te anti-infam- chlorogenic, and cafeic acids [84–88]. Diferent mecha- matory efect of carob leaves was attributed to its polyphe- nisms can therefore be proposed to explain the weight- nols which might relieve infammation severity linked with reducing efects of M. spicata including inhibiting pancre- obesity and colitis. atic lipase activity, promoting lipolysis, decreasing nutrient Te present results as well as a review of the available absorption, reducing adipocytes diferentiation, stimulating literature have led us to believe that carob products can thermogenesis and lipid metabolism, inhibiting oxidative exert their antiobesity efect through the following main basic stress and infammation, inhibiting synthesis of plasma, hep- mechanisms (Figure 5): inhibiting pancreatic lipase activ- atic cholesterol, and triacylglycerol, and controlling appetite ity, impairing adipogenesis, promoting lipolysis, increasing (Figure 6). thermogenesis and fat oxidation, suppressing chronic low- Sarcopoterium spinosum is a widely distributed chamae- grade infammation, enhancing cellular antioxidant defenses, phyte of the Rosaceae family growing in the eastern Mediter- reducing absorption of lipids, and controlling appetite. How- ranean region. Te shrub is mentioned as a medicinal plant ever, the relative role of these mechanisms would depend on in several ethnobotanical surveys, documenting the use of the type of carob product and diet consumed by individuals as S. spinosum aqueous root extract by traditional medicinal well as the dietary conditions. Our results indicate that carob practitioners for the treatment of diabetes and pain relief products might be a powerful lipase inhibitor and could be (e.g., toothache), as well as cancer therapy [41, 89–92]. Te used as a weight control in obese patients. glucose lowering properties of the plant’s roots, leaves, and Curcuma longa (turmeric) is a rhizomatous herbaceous fruits have been demonstrated by Elyasiyan et al. [93]. Te perennial plant of the ginger family, Zingiberaceae. Turmeric plant’s glucose lowering agents (bioactive polyphenols, e.g., isacommonlyusedspiceandiswelldocumentedforits catechin) target insulin afected tissues (e.g., liver, muscle, and medicinal efects in Indian and Chinese medical systems; the adipose tissue) leading to inhibiting carbohydrate digestion, plant is recognized for its anti-infammatory, antiangiogenic, enhancing insulin secretion, and improving the transmission antioxidant, wound healing, and anticancer properties and of insulin signaling in adipocyte and myotypes, leading to health promoting properties [74, 75]. In TAPHM the rhi- enhancing glucose uptake, metabolism, and regulation of zomesoftheplanthavebeenreportedtobeusedforthe whole body energy balance [93, 94]. 16 Evidence-Based Complementary and Alternative Medicine

Termogenesis Pancreatic lipase Polyphenols and favonoids: epicatechin, epicatechin Fat oxidation gallate, and myricetin Adipogenesis

Antioxidant Appetite

Lipolysis Infammation Lipids absorption

Figure 5: Antiobesity mechanisms and related benefcial efects of Ceratonia siliqua extracts and their bioactive constituents.

Cholesterol and Antioxidant triacylglycerol

FlavonoidsFlavonoids & phenolicphenolic acids:acids: catechin, epicatechin, Adipocytes Termogenesis myricetin,myricetin, naringeninnaringenin diferentiation & rosmarinic acid Adipogenesis Lipolysis

Nutrient Pancreatic absorption lipase

Infammation Appetite

Figure 6: Antiobesity mechanisms and related benefcial efects of Mentha spicata extracts and their bioactive constituents. Evidence-Based Complementary and Alternative Medicine 17

AMP-activated Pancreatic protein kinase lipase CatechinsCatechins & triterpenoids:triterpenoids: epepigallocatechinigallocatechin gallate,gallate, epicatechinepicatechin lipid and Calorie intake ggallate,allate, epepicatechin,icatechin, protein epigallocatechinepigallocatechin & tormentictormentic acidacid absorption

Adipogenesis Hyperglycemia

Infammation Insulin Appetite resistance

Figure 7: Antiobesity mechanisms and related benefcial efects of Sarcopoterium spinosum extracts and their bioactive constituents.

In our study the plant aerial parts extracts were among possessing weak antioxidant activity by both methods. Tese the top 5 most active PPLI plant extracts by means of include Elaeagnus angustifolia, Alchemilla xanthochlora, Cas- IC50 (1.2mg/mL).Tiscanbeattributedtothefactthat sia senna, Malva sylvestris, Cuminum cyminum, Cynara scoly- the Sarcopoterium extracts contain an array of bioactive mus (fruit bulb and husk), and Eruca sativa; these plants ingredients including polyphenols and favonoids known as can be considered as potential PPL inhibitors but not as catechins, which include (−)-epigallocatechin gallate, (−)- antioxidants. On the other hand, the epicarp of Rhus coriaria, epicatechin gallate, (−)-epicatechin, (−)-epigallocatechin [92, the seeds of Lepidium sativum, and the leaves of Cupressus 95, 96], and triterpenoids such as tormentic acid [97, 98] and sempervirens and Olea europaea could be considered as �-tocopherol[99]thatpossessantiobesityproperties[93]. alternatives to antioxidants, but not as antilipase sources. Our results are in concordance with those of Tovit et al. It is worth noting that 76.9 % of the plants analyzed [100] and Rozenberg et al. [94] which also suggest that the inthisstudywerereportedtobeusedinPalestineasfood bioactive plant extracts have various benefcial antiobesity either in the form of tea, salad, and condiment or in cooked efects such as inhibiting lipolysis in an adipocyte, inducing form [51]; of these plants 41.7 % ( 25 plant extracts) possess glucose uptake in a cell, reducing plasma glucose levels, pre- PPLIactivityofmorethan50%.Teuseoftheseplants venting atherosclerosis, decreasing weight gain, decreasing asfoodsuggeststhattheyaresafeandcanbeusedinthe food consumption, and/or reducing or preventing obesity. management of obesity and as natural antioxidants. All plant Sarcopoterium-derived polyphenols are expected to species analyzed in this study for their antioxidant and PPLI reduce obesity and decrease the adverse health efects of obe- potentials were mentioned to be used in TAPHM for the sity and related complications by producing diferent physio- treatment of several human ailments [40]. On the other logical efects, including weight-reducing efects through the hand, of the 41 plant extracts reported by the Palestinians following basic mechanisms (Figure 7): inhibiting pancreatic to be used for the treatment of obesity (Table 1), 18 plant lipase activity and decreasing absorption of lipids and pro- extracts have shown to possess PPLI activity of > 50 %. teins in the intestine, thus reducing calorie intake, impairing Our results support these ethnobotanical studies and suggest adipogenesis, suppressing appetite, enhancing the activation that these plants may serve as the basis for the development of AMP-activated protein kinase in the skeletal muscle, adi- of novel antioxidants and antiobesity pharmaceuticals and pose tissues, and liver, and improving systemic infammation, nutraceuticals/functional foods. hyperglycemia, and insulin resistance [56, 58, 59, 93]. Table 2 shows that antilipase activity is not necessarily 5. 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