Journal of Coastal Life Medicine 2014; 2(10): 826-840 826

Journal of Coastal Life Medicine

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Document heading doi:10.12980/JCLM.2.2014C1221 2014 by the Journal of Coastal Life Medicine. All rights reserved. 襃 tinctoria R. Br.-a review on its ethnobotany, pharmacognosy and pharmacological profile

1* 2 Mahendra S. Khyade , Nityanand P. Vaikos 1Department of Botany, Sangamner Nagarpalika Arts, D. J. M. Malpani Commerce and B. N. Sarda Science College, Sangamner, Sangamner-422 605 (MS), 2Department of Botany, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, India. Presently at Sonchafa, Plot No. 15B Mahavir Nagar, Osmanpura Aurangabad, India.

PEER REVIEW ABSTRACT

Peer reviewer W. tinctoria Different parts of R. Br. () ( ), have been extensively Prof. Chumbhale DS, Department of used in Indian systems of medicine such as Ayurveda, Siddha and Unani for the treatment of Pharmacognosy, Amrutvahini College jaundice, malaria, psoriasis and many other ailments. The present review has been primed to 422 608 of Pharmacy, Sangamner- , describe the existing data on the information on the traditional uses, botanyW., p htinctoriaarmacognosy, Maharashtra, India. phytochemical constituents, pharmacological activities and toxicology of . The Tel: +91 9922256665 information was gathered via electronic search (using Google Scholar, NOPR, Pubmed, Elsevier, E-mail: [email protected] Medline Plus and Web of Science) and library search for the books on traditional medicine as well Comments as the articles published in peer-reviewed journals. The is rich in compounds containing O ( ) alkaloids, saponins, inβdoxy yielding -glycoside s , phenolics, flavonoids, isatin tryptanthrin, T h e p r e s e n t r e v i e w p r o v i d e s anthranillate, rutin, -isatin, tryptophan, indigotin, indirubin, wrightial and sterols. TW.he comprehensive information on the tinctoriavast number of literature found in database revealed that the extracts of different parts of traditional uses, ethnopharmacology, showed significant pharmacological actions. Clinical studies indicated a broad range pharmacognosy, phytochemistry, of applications in the treatment of psoriasis and other skin diseases. We suggest that there is a biological activities, pharmacologicW.al need for further investigations to isolate active principles that confer pharmacological action. atinctoriactivities and toxicology of Therefore, identification of such active compound is useful for producing safer drugs in the . The data provided in the treatments of various ailments. present manuscript is worthy and KEYWORDS written in good format of the journal. Wrightia tinctoria Details on Page 836 , Ethnobotany, Traditional uses, Pharmacognosy, Pharmacological profile

1. Introduction to have medicinal properties and have a long history of use by indigenous communities in India[2]. The medicinal Wrightia tinctoria W. tinctoria R. Br., (Apocynaceae) ( ), value of this plant for the treatment of a large number e.g. a small deciduous is known by various names, of human ailments is mentioned in Ayurveda, Siddha, Ivory tree, Easter tree, Sweet indrajao and Pala indigo- Unani and folk medicine[3-6]. In the last more than three plant (English). In India, it is locally recognized by its decades, several studies have been carried out on this different vernacular names, the most commonly used ones medicinal plant species to facilitate evidence in favor of are Indrajava, Svetkutaja, Krsnkutaja (Sanskrit), Kalakuada its conventional uses. The rationale of this review is to (Marathi) and Mitha indrajau (Hindi)[1]. The whole plant provide comprehensive information on the traditional uses, or its specific parts (bark, , seed and root) are known ethnopharmacology, phytochemistry, pharmacological

*Corresponding author: Mahendra S. Khyade, Department of Botany, S. N. Arts, D.J. Article history: Malpani Commerce and B.N. Sarda Science College, Sangamner -422 605 (MS), India. Received 23 Feb 2014 E-mail: [email protected] Received in revised form 20 Mar, 2nd revised form 2 Apr, 3rd revised form 19 Apr 2014 Tel: +91 9421482234 Accepted 6 Jun 2014 Fax: +91 2425 225893 Available online 25 Sep 2014 Mahendra S. Khyade and Nityanand P. Vaikos/Journal of Coastal Life Medicine 2014; 2(10): 826-840 827 W. tinctoria research and toxicology of to explore its Stamens are at the top of the corolla tube. Filaments are therapeutic potential, highlight the lacunae in our present short, dialated, anthers exserted, sagittate conniving around knowledge and explore future research possibilities. and adhering to the stigma. The ovary is of 2 carpels, free or connate; ovules many in each carpel. Fruits are made of 1.2. Geographical distribution and ecology 2-distinct pendulous, follicles 20-40 cm long, cylindrical, slightly tapering to both ends, glabrous, striate, cohering at W. tinctoria The plant of is widely distributed in Asia, first at the tip only. Seeds are 1.2-2.0 cm long, pointed at the Africa and and are known to be the native of apex with deciduous coma often more than 3.0-3.7 cm long Australia, India, , and [1]. The plant at the base[9,10]. mostly occurs in the Western, Central and Peninsular India[7]. The plant grows well in arid, semi-arid and moist regions 2. Traditional uses with a wide range of soil types. This plant is especially common along hillsides and valleys and is often found as i.e W. undergrowth in deciduous forests. The timber . white wood Numerous traditional uses have been recorded for tinctoria is of high quality and value for turnery, carving, toy making, [2]. In Karnataka and Tamilnadu (states of India), the “ ” matchboxes, small boxes and furniture. , flowers, tree named as jaundice curative tree , since the juice of fruits and roots constitute the source of an indigo-yielding its tender leaves is used as an effective drug for treatment glucoside, which produces a blue dye or an indigo dye[8]. of jaundice[11]. Fresh leaves are pungent and when crushed fresh leaf filled in the cavity of decayed tooth or chewed 1.3. Botanical description under tooth relieves toothache. Juice of leaves is also employed against serpent bite and considered febrifuge, W. tinctoria is a small deciduous tree, 5-8 m tall and has stomachic and tonic[2,3,11-13]. a scaly, smooth bark. Leaves are variable, 6-15 cm伊3-6 In Siddha medicine, the plant is widely used in the cm, elliptic-lanceolate or oblong-lanceolate, acuminate, treatment of psoriasis and other skin diseases[4,7,14]. Leaves glabrous or the young leaves puberous beneath, base acute soaked in coconut oil are kept in hot sunlight for a day and or rounded; main nerves 6-12 pairs and petioles 3-4 mm then this oil is used for the treatment of psoriasis[15-17]. Oil long. Flowers are white, fragrant, in lax terminal cymes, 777 prepared from fresh leaves of plant with coconut oil bracts minute, ovate. Calyx is glabrous, glandular inside, has been assigned to be analgesic, anti-inflammatory and segments or teeth 2.2-5.0 mm long, oblong, rounded at the antipyretic activities[18], to be effective in the treatment of apex and with membranous margins. Corolla tube is short, psoriasis[19]. 2.5-3.0 mm long, white, lobes 6-8 mm long, oblong and Bark is used as tonic, anthelmintic, antidiarrheal, obtuse. Corona consists of numerous linear scales, some febrifuge and aphrodisiac; it is used in treatment of seminal inserted with the filaments and some on the corolla-lobes weakness, flatulence, colic diarrhea, leprosy, psoriasis, (Figure 1). haemorrhoids dipsia, helminthiasis fever, digestive, stomachic, constipating, depurative, febrifuge, burning sensation and dropsy[4,11,12,20,21]. Seeds are useful as a tonic, carminative, anthelmintic, astringent, aphrodisiac and febrifuge and for treatment of stomach disorder[20-22]. In Unani medicine, the seeds of Wrightia “ ” are differently known as Lisanul-e-Asafir , Inderjao Shireen, and Meetha Inderjao and have been reported to have used for cure disorders of central nervous system and claimed to have analgesic, aphrodisiac, tonic W. tinctoria and emmenagogue actions[3,5,6,21]. have been recommended for the treatment of infections of the chest (in asthma), colic and as diuretic[3]. Extracts of the root and leaves possess hypotensive activity[1]. According to an ethnobotanical information, the plant Figure 1. W. tinctoria. Flowering twig of bark is of considerable medicinal value for bronchitis, piles Mahendra S. Khyade and Nityanand P. Vaikos/Journal of Coastal Life Medicine 2014; 2(10): 826-840 828 3. Pharmacognostical studies and is used in scorpion sting and snakebite[23]. In Nasik district of Maharashtra state of India, infusion of bark is 3.1. Leaves administered to mothers for a week to increase lactation[24]. People inhabiting in Seshachalam hills of Andhra Pradesh, India apply a paste of crushed stem bark along with bark The leaf is dorsiventral and amphistomatic. The stomata Ailanthus excelsa of on wounds once in a day for 3 d[25]. are paracytic. The trichomes are 3-7 celled, thick walled and In tribal villages of Chitheri Hills of Dharmapuri district uniseriate. Adaxial epidermis has striations. Mesophyll is in Tamilnadu, the bark decoction is given to cure piles, differentiating into 1-layered palisade and spongy tissue of whereas bark and seeds are used together to treat various loosely arranged cells. Midrib shows an arc shaped vascular ailments[26]. A crushed fresh leaf when filled in the cavity of bundle. In quantitative microscopy, the stomatal indexes decayed tooth relieves toothache[27]. The native practitioners have been found to be 21.0. Vein islet number and vein-let in and around Chitoor district, India, have claimed that termination number are 21.0 and 21.8 respectively[58-60]. The W. tinctoria the leaves of are used for treating diabetes[28]. histochemical color reactions were carried out in transverse Tribes of Southern Rajasthan use the latex of plant externally section of the fresh leaf. The results indicated the presence of on vagina for easy delivery[29]. These claims of medicinal lignin, starch, fats, alkaloids, saponins, tannins, flavonoids and properties are to be substantiated by clinical trials in calcium oxalate crystals. Histochemical localization of certain humans. Table 1 summarizes ethnomedicinal uses reported important compounds enables to get a preliminary idea of type W. tinctoria for [30-57]. of compounds and their accumulation in the plant tissues[60].

Table 1 W. tinctoria. Ethnomedicinal uses of Plant part Method of preparation Use References Leaf Paste Skin diseases; external and internal application [30] Paste Toothache and swelling gums [31,32] Pounded leaves mixed with coconut oil Eczema, psoriasis and other skin diseases [33-39] Unspecified Skin disease, wound healing [40] Juice mixed with lime and turmeric powder Swellings [25,41] Infusion from coconut oil Chronic wounds (veterinary medicine) [31] Santalum album Allium cepa Paste with and Chronic wounds (veterinary medicine) [31] Juice Jaundice [42] W. tinctoria Azadirachta indica Oil obtained from the paste of leaves of and Eczema [33,43] Half a teaspoon of dried leaf powder Respiratory ailments [44] Ailanthus excelsa Stem bark crushed with those of , paste applied daily once Bark Boils, wounds [25] for 3 d Powdered and mixed with coconut oil Wounds [45] Unspecified Galactogogue, abdominal pain [46] Unspecified Antipyretic [47] Unspecified Cure skin diseases, wounds [40,48] Unspecified Antidote for snake poison [49] Decoction Antidysenteric, antidiarrhoeal and antihaemorrhagic agent [50,51] Paste Skin diseases, ringworm and in leprosy [52] Infusion Stomach disorder [53] Stem Unspecified Toothbrush [31] Decoction Cure stomach disorder [44] Latex Unspecified Skin disease, wound healing [40] Root Decoction Epilepsy [54] Unspecified Laxative [40] Decoction Cure stomach disorder [44] Whole plant Unspecified Antioxidant, Antinociceptive [55] Seed Powdered and mixed with coconut oil Wounds [45] Unspecified Piles, worm infestation and pain [51] Juice Indigestion [56,57] Unspecified Decoction Wounds [45] Mahendra S. Khyade and Nityanand P. Vaikos/Journal of Coastal Life Medicine 2014; 2(10): 826-840 829 3.2. Bark presence of bioactive phytoconstituents in leaf, bark, W. tinctoria root and seed of . Preliminary phytochemical Transverse section of bark consists of tangentially screening of the leaves showed the presence of alkaloids, elongated thick walled, suberised 6-8 layers of cork cells, cardiac glycosides, flavonoids, tannins, terpenoids[60,66-68]. arranged in radial alignment or rows followed by phellogen Further detailed phytochemical characterization studies composed of tangentially elongated parenchyma cells. reveal presence of triacontanol and tryptanthrin[69] along Phelloderm is a wide, parenchymatous and interspaced with indigotin, indirubin, tryptanthrin, isatin, indoxyl- with phloem fibers and stone cells. The ground tissue has yielding O-glycosides, rutin and anthranillate[70]. However, stone cells in old bark. Starch grains and prisms of calcium indirubin has been reported only in the dried leaves and oxalate crystals are present in parenchyma cells. Phloem not in freshly collected ones[70]. Furthermore, content of fibers and medullary rays are mostly uniseriate and few are indigotin and indirubin depends on seasonal variation. biseriate[59,61,62]. Interestingly, taxol, an anticancer drug, which in vitro exhibited strong cytotoxic activity in the apoptosis 3.3. Seed Phyllostica assay; isolated from a leaf spot fungus, tabernaemontanae W. tinctoria , of leaves of [71]. Similarly, a Holarrhena antidysenterica “ ” Seeds of are well known new protease named Wrightia purified from the latex of W. W. tinctoria to treat dysentery and are confounded with those of the plant is thought to be a potential candidate tinctoria . A comparative pharmacognostical study was for various applications in food and biotechnological “ ” carried out on seeds of both the species. The seeds of industries[72]. The 777 oil , a coded drug of Siddha the former taxon have been characterized by having system of medicine, has been derived from the leaves of W. tinctoria W. tinctoria hairs on the micropylar whereas in they are by insulation with coconut oil as a base. This developed at the chalazal end. The seeds of these two process of preparation in the Siddha medicine is called “ ” et al taxa have different patterns of folding of cotyledons and Sooriya Pudam [15]. Alam . suggests modifications “ ” W. tinctoria spermodermal ornamentation as well. Heavy tanniferous in 777 oil by employing the bark of instead deposition in the outer epidermal cells of the seed coat of leaves[73]. Thin layer chromatography characterization H. antidysenterica W. in and its scanty deposition in of both the products reveals that they are chemically tinctoria is also an additional character to be used as a identical. W. tinctoria distinguishing feature[63-65]. The stem bark of reported to contain β β -amyrin, lupeol, -sitosterol, stigmasterol, campesterol 3.4. Root and a triterpenoid, flavonoid, steroids, alkaloids and phenolics[59,62,74-76]. Root epidermis is composed of compactly arranged The mature powdered pod showed the presence of co- β smaller cells. Periderm formation has been observed. Many occurrence of -amyrin, ursolic acid and oleanolic acid β layered cork is made up of radially aligned rectangular along with -sitosterol[77]. The wrightial, a new terpene cells. Below it lies many layered cortex and phloem. and other phyto constituets such as cycloartenone, β β Phloem cells show the presence of starch and oxalate cycloeucalenol, -amyrin and -sitosterol were isolated crystals. Secondary growth is more. Xylem occupies a from methanol extract of the immature seed pods[78]. α considerable part. Medullary rays are made up of 1-2 rows In addition to this, a new sterol 14 -methylzymosterol of cells. Vessel elements in the roots are variable in length along with four rare plant sterols, desmosterol, and diameter with simple perforations. Pits are simple, clerosterol, 24-methylene-25-methylcholesterol and alternate and thickly arranged. The tail is short or long 24-dehydropollinastanol have also been obtained from with mostly pointed end[59]. seeds[79]. The hexane extract of seed pods contains oleonolic acid[77]; whereas ursolic acid and isoricinolic acid have been further separated from the seedpods and 4. Phytochemistry W. tinctoria seed oils[80]. Thus far, root of received less research interest pertaining to phytochemical constituents. Most of the health promoting and disease curing potential However, our preliminary phytochemical studies of root of and their plant products are associated to their reported the presence of cardiac glycosides, saponins, phytoconstituents. Accumulating evidence showed the pseudotanins and terpenoids[59]. Mahendra S. Khyade and Nityanand P. Vaikos/Journal of Coastal Life Medicine 2014; 2(10): 826-840 830 5. Biological and pharmacological activity Staphylococcus aureus and 0.25 mg/mL for ) whereas, hexane extract found to be potent against dermatophytic W. tinctoria Trichophyton rubrum Trichophyton So far, has been reported to possess an array fungi such as and tonsurans of biological and pharmacological properties that include at 2 mg/mL[85]. Similarly, in another study, etc. in vitro antidiabetic, antimicrobial, antimalarial, anthelmintic, antibacterial activities of the petroleum ether, W. chloroform, methanol and water extracts of leaves of 5.1. Antidiabetic activity tinctoria Staphylococcus aureus S. were studied against ( aureus Escherichia coli E. coli ) (Gram-positive) ( ) (Gram- Diabetes is one of the prevalent diseases of carbohydrate negative) as test organisms[86]. The chloroform extract of W. tinctoria E. metabolism, resulted into hypoglycemic condition. It has registered the highest zone (24 mm) against coli S. aureus been observed that hyperglycemic condition leads to , followed by aqueous extract with (12 mm) and E. coli various complications such as retinopathy, nephropathy, (14 mm). The antibacterial study of different solvent etc et al . Zito . studied ocular aldose reductase inhibitory extracts such as petroleum ether, chloroform, acetone and W. tinctoria W. tinctoria activity to at 1 mg/mL as aldose reductase methanol of leaf has been carried out in our and sorbitol dehydrogenase to accelerate the formation of laboratory. It was a chloroform extract that exhibited the S. aureus sorbitol from glucose in insulin-sensitive tissue leading to highest antibacterial activity against (24 mm), i.e E. coli Salmonella typhi Pseudomonas aeruginosa the development of cataracts in lens . one of the common , and P. aeruginosa nephropathic condition in diabetes[81]. The results of this ( )[87], followed by acetone and methanol W. tinctoria study showed that strongly inhibits aldose extracts. Interestingly, the observed antibacterial activity µ et reductase (92.92%) with IC50 5 g/mL[81]. Similarly, Kumar is almost equal, and/or more when compared to standard al W. . have reported alpha glucosidase inhibitory activity of ampicillin[87]. Indirubin isolated from the chloroform extract tinctoria W. tinctoria [82]. Results showed that the bark ethanol extracts of leaves of tested for its antibacterial activity in vitro S. aureus P. aeruginosa etc. have significant intestinal alpha glucosidase on , and efflux pump inhibitory inhibitory activity at 1 500 mcg/mL[82]. (EPI) activity. Indirubin showed antibacterial activity against et al Raj . investigated the hypoglycemic and both Gram-positive and Gram-negative strains; and drug W. S. aureus hypolipidemic activity of petroleum ether extract of resistant to ; the observed MIC was 12.5 mg/mL for tinctoria S. aureus Streptococcus epidermidis W. in alloxan induced diabetes in albino Wistar and 25 mg/mL for . tinctoria rats[83]. Oral administration of petroleum ether leaves had significant EPI property and further clearly extracts at doses 200 and 400 mg/kg exhibited a significant showed the synergistic effect along with ciprofloxacin. This reduction in elevated levels of serum glucose, total indicated that indirubin has the capacity to block the Nor cholesterol, and triglycerides. The results of this work A efflux pump, which leads to cell susceptibility, due to W. tinctoria confirmed have significant application in increasing concentration of ciprofloxacin within the cell[88]. Pityrosporum ovale P. ovale diabetes mellitus illness and its related complications[83]. ( ) is a yeast causing infection Later, these investigators also reported the antidiabetic of skin and scalp leading to dandruff. Krishnamoorthy W. tinctoria in vitro effect of petroleum ether extract of leaves in and Ranganathan studied antifungal activity of the W. tinctoria Hibiscus streptozotocin induced diabetic rats[84]. oil made from leaf extracts of and rosasinensis P. ovale against [89]. The results of this study 5.2. Antimicrobial activity µ indicated MIC ranges between 500-1 000 g/mL indicating fungicidal action of the drug. et al Antimicrobial effect investigations provide rationale Anbuganpathi . also studied the antibacterial and W. tinctoria information for the traditional uses of in antifungal effect of chloroform and aqueous extracts of W. tinctoria treating microbial infections such as the dental diseases, [90]. Interestingly, the authors reported no dysentery, respiratory ailments, psoriasis and other skin antifungal activity of all the studied extracts, but good diseases. The leaves hold potent antimicrobial properties bactericidal activity was reported to all the studied et al et al in vitro against dermatophytic microbes. Kannan . screened extracts[90]. Similarly, Krishnamoorthy . studied in vivo different solvent extracts against skin bacteria and and antifungal effect of the Dano, a poly-herbal hair W. tinctoria Cassia alata dermatophytes[85]. The methanol and ethanol extracts were oil, containing extracts of , and Azadirachta indica found to be more active against studied bacteria (at MIC [91]. The results of this study also showed Bacillus subtilis, Staphylococcus epidermidis P. ovale Candida 0.5 mg/mL for that Dano inhibited the growth of and Mahendra S. Khyade and Nityanand P. Vaikos/Journal of Coastal Life Medicine 2014; 2(10): 826-840 831 albicans Culex quniquefasciatus with MIC at 30 mg/mL and 50 mg/mL respectively. against [98]. Further clinical studies on 10 volunteers with severe 5.4. Anthelmintic activity dandruff in the age group of 18-22, showed mild traces to nil scaling with successive days of treatment[91]. Vijaykumar et al W. tinctoria .[92] carried out an investigation of leaf Anthelmintic activity of crude petroleum ether and W. tinctoria extracts along with other species for the antimycotic activity chloroform extracts of leaves of using P. oval Pheretima posthuma against and showed the antifungal property as they as a model organism were studied at P. ovale progressively inhibited the growth of on saboured three concentrations (2.5, 5.0, 7.5 mg/mL) of each extract. W. tinctoria dextrose agar medium[92]. It was reported that the methanol Petroleum ether and chloroform extract of and chloroform extract prepared from the woody stem bark caused significant paralysis (125.83 and 94.5 seconds) and W. tinctoria Pheretima posthuma of indicated the broad spectrum and significant death (162.33 and 140.28 seconds) of . antimicrobial activity against various microbes used[74]. respectively[99] Minimum time taken by the methanol W. tinctoria In addition, we have demonstrated potent antibacterial extract of leaves (100 mg/mL) were 13.97 activity of chloroform extract followed by acetone and and 23.3 min to cause paralysis and death of the worms methanol extracts, while petroleum ether indicated negative respectively[100]. et al inhibition[93]. Jayechandran . screened the antibacterial W. tinctoria viz. 5.5. Analgesic and anti-inflammatory activity potential of using various solvents , hexane, petroleum ether, ethyl acetate, chloroform, acetone and E. coli et al methanol on bacterial cultures of (MTCC 1195), Reddy . evaluated the antinociceptive activity of Klebsiella pneumoniae Enterobacter aerogens (MTCC 2405), petroleum ether, chloroform, ethyl acetate, acetone and S. typhi Proteus vulgaris W. tinctoria (MTCC 2823), (MTCC 733), (MTCC 1771), methanol extracts of bark on acetic acid- P. aeruginosa S. aureus Bacillus (MTCC 2642), (MTCC 1430), induced writhing test in mice[101]. The ethyl acetate, acetone cereus (MTCC 1272)[94]. Petroleum ether, chloroform, acetone and methanol extracts showed significant antinociceptive and hexane extracts showed the highest inhibition zone activity and were comparable with acetylsalicylic acid[101]. E. coli, Proteus mirabilis et al between 19-22 mm against and In the study of Bigonia . in 2008, the ethanol (70%) Klebsiella pneumoniae W. tinctoria , respectively, while the moderate extract of bark showed significant analgesic ’ antibacterial activity was attributed to hexane, acetone and activity in Eddy s hot plate reaction and tail flick method. chloroform extracts[94]. In another study, hexane, methanol, The authors claim the observed analgesic activity could be W. chloroform, ethyl acetate and water extracts of leaves of due to the presence of steroids in the extract and concluded tinctoria in vitro W. tinctoria were subjected to antibacterial screening that bark extract is effective against acute against plant pathogenic bacteria using disc diffusion phasic pain[102]. et al method[95]. Results showed that ethyl acetate and methanol In another experiment, Tharkar . investigated for extracts have significant antibacterial activity against anti-inflammatory activity of bark in carrageenan-induced µ Xanthomonas Gram-negative bacteria with MIC 50 g/mL for rat paw oedema and cotton pellet induced granuloma campestris Erwina and sp. animal models[103]. The results of this study exhibited that the aqueous and chloroform extract treated group showed 5.3. Antimalarial activity P significant ( <0.05) reduction in paw oedema from 4-5 h, while methanolic extract and diclofenac sodium treated W. P Tryptanthrin, an indolquinazolin isolated from group showed a significant reduction ( <0.05) in paw tinctoria Plasmodium leaves[70], was tested against oedema from 2-5 h when compared to control group[103]. falciparum . Further, tryptanthrin and several of its Further, the observed anti-inflammatory activity of Plasmodium falciparum W. tinctoria analogues were also tested for chloroform extract of bark was attributed to the and showed very low IC50 values: 69 ng/mL for tryptanthrin presence of the flavonoid[104,105]. Jain and Bari investigated and 0.43-10 ng/mL for analogues. These compounds were anti-inflammatory activity of petroleum ether and methanol W. tinctoria particularly active against atovaquone-, chloroquine- or extracts of bark using carrageenan and mefloquine-resistant strains[96]. Valanite reported that the histamine-induced paw edema animal models[106]. The observed antimalarial activity of tryptanthrin could be due results of this study exhibited that the extract possessed to its immunostimulating potential[97]. In addition to this, significant dose dependent anti-inflammatory activity. W. tinctoria et al leaves of are known to possess larvicidal effects Aleykutty . studied analgesic and anti-inflammatory Mahendra S. Khyade and Nityanand P. Vaikos/Journal of Coastal Life Medicine 2014; 2(10): 826-840 832 W. tinctoria effects of leaf extract in rats and mice[107]. The The plant methanolic extract showed significant gastro anti-inflammatory effect was investigated by human red protective activity (65.89%), when compared with the blood cell membrane stabilization method and carrageenan standard drug famotidine (20 mg/kg). The results suggested W. tinctoria induced hind paw edema method. Ethyl acetate fraction that the methanolic extract of leaves possess showed 67.21% protection at concentration 400 mg/kg. anti-ulcer effect[112]. The ethyl acetate fraction was studied for its analgesic 5.7. Immunomodulatory activity effect on acetic acid-induced writhing test and hot plate method in mice and was found to be effective. Above W. tinctoria et al W. findings justify the traditional use of leaves Bigonia . reported immunomodulatory activity of tinctoria against inflammation and pain in psoriasis, hemorrhoids bark alcohol extract on nonspecific and specific and swelling gums[107]. The leaves revealed different immune responses, studying the parameters such as survival constituents such as flavonoids, steroids, glycosides, study, carbon clearance test, delayed type hypersensitivity W. tinctoria saponins, sterols, tannins and phenolics. Phenolics possess and hemagglutinating antibody titer[113]. extract various biological properties such as antioxidant, anti- at 400 mg/kg body weight increased the survival rate of E. coli inflammatory and estrogenic activities[108]. Phenolics rats against induced abdominal sepsis up to 15 d and flavanoids were used for the prevention and cure of post infection. The extract showed significant homeopathic various diseases, and mainly associated with free radicals. activity and raised neutrophils count significantly, which Flavanoids are known to possess anti-inflammatory was further confirmed by increased phagocytic response W. tinctoria activity by inhibiting the cycloxygenase responsible for the against inert particles. exhibited decreases in synthesis of inflammatory prostaglandins[109]. In addition, delayed type hypersensitivity response. Further, extract W. tinctoria flowers of depicted anti-inflammatory activity enhanced both primary and secondary humoral responses as revealed by Sethuraman[110]. in rats sensitized with bovine serum albumin. The results of W. tinctoria this study substantiate that bark extracts have 5.6. Antiulcer activity moderate non-specific immunostimulant[113]. In another et al study, Thabah . investigated the immunomodulatory et al. Bigonia reported antiulcer activity to bark ethanol activity of the bark extracts such as petroleum ether, W. tinctoria extract against experimental induced acute gastric ulcer ethanol and aqueous alcohol of by using model[111]. The extract significantly reduced the ulcer index delayed type hypersensitivity reaction and carbon clearance induced by both pyloric ligation and ethanol at 100 mg/ assay[114]. Petroleum ether and aqueous alcohol extracts p.o. kg dose; similarly, extract treatment significantly reduced (200 and 400 mg/kg, ) produced a significant increase the secretary parameters such as volume and pH of gastric in delayed type hypersensitivity in response to sheep red juice, free and total acidity. The extract has a significant blood cells. Petroleum ether extract showed better activity effect on gastric mucous substances. By increasing than aqueous alcohol in delayed type hypersensitivity total carbohydrate content and decreasing total protein response. Aqueous alcohol extracts at dose 200 and 400 mg/ p.o content in pyloric ligated ulceration, all these effects are kg, ., showed a significant dose dependent increase in comparable to ranitidine (20 mg/kg). The results indicated the phagocytic activity. The results revealed that aqueous W. tinctoria that bark extract protects gastric mucous alcohol possesses immunostimulant activity in carbon membrane by improving microcirculation, increased clearance assays whereas the petroleum ether extract and capillary resistance or by precipitating microproteins. In aqueous alcohol showed immunomodulatory activity in the another study, Divakar and Devi evaluated antiulcer activity delayed type hypersensitivity model[114]. W. tinctoria of leaves of evaluated against experimentally 5.8. Wound healing activity induced acute gastric ulcer model in albino rat[112]. The antiulcer activity of methanol was evaluated by comparing W. with carboxy methyl cellulose, pylorus control, aspirin and The aqueous and alcoholic extracts of the stem bark of tinctoria standard famotidine, by employing aspirin plus pylorus were investigated for their antipyretic and wound ligation induced ulcer model. The biochemical parameters healing potential in albino rats using excision model. such as volume of gastric juice secretion, pH, free acidity, Wound healing activity was assessed by the percentage of total acidity, ulcer index and percentage inhibition were wound contraction and the period of epithelization; there studied at the concentration of 200 mg/kg body weight. was wound contraction activity by using extracts from the Mahendra S. Khyade and Nityanand P. Vaikos/Journal of Coastal Life Medicine 2014; 2(10): 826-840 833 14th day of topical application. Further, yeast induced 5858372), obtained from the pharmaceutical preparation for pyrexia model was used for evaluation of antipyretic topical treatment of skin disorders, particularly psoriasis, activity in albino rats and fall in body temperature of comprises the ingredients of latex extracted from the leaves W. tinctoria febrile rats was taken as an indication of antipyretic action. of , urea and polyethylene glycol[121]. The drug extracts had significant antipyretic activity[115]. In the case of allergies of externally manifesting as Jain and Bari reported the potential effect of petroleum urticaria, eczema and psoriasis, a specific plant drug store W. tinctoria ether and methanolic extracts of bark in wound healing in cottage ( ) has been tried in the form of an oily Wistar albino rats[116]. The wound healing parameters were extract for the treatment of psoriasis with encouraging evaluated by using incision wounds in extract-treated rats, results. Fresh leaves of the plant are crushed and kept standard and controls. Both 5% and 10% doses of petroleum embedded in coconut oil under the sun for 5-7 d and the ether and methanol extract significantly increased wound oil is subsequently filtered out. This oil is used for local breaking strength when compared with the control group application and for oral administration in doses of 5 mL and the ethanol extract indicated, wound healing effect in twice a day for 3 months. Trials made in a series of 40 the rats[117]. The observed significant wound healing activity patients showed significant relief in symptoms, reduction in was attributed to the presence of antioxidant compounds scaling and shrinkage of the affected surface area. The drug such as flavonoids and saponins. The enhanced wound does not show any side effects[16]. healing may thus be due to the free-radical scavenging 5.10. Other activities action of the plant, enhanced level of antioxidant enzymes in the tissues, antimicrobial potential which control W. tinctoria microbial colonization and subsequent proliferation. was reported to have hepatoprotective activity[122]. Further, Bigoniya and Rana investigated the 5.9. Effect against psoriasis and other skin diseases hepatoprotective effect of triterpene fraction isolated from W. tinctoria β the stem bark of (containing lupeol, -amyrin β Psoriasis is a chronic recurrent problem affecting the and -sitosterol) against CCl4-induced hepatotoxicity skin, nails, and joints and it is one of the papulo-squamous in comparison with known standard sylmarin in the disorders. The current treatments available for psoriasis rat[123]. Pretreatment with triterpene fraction 125, 250 p.o. include local application of emollients, moisturizers, and 400 mg/kg, once a day for 4 d before CCl4 and tars, anthralins, topical corticosteroids, vitamin A and continued further 3 d, attenuated the CCl4-induced acute D analogs and systematic treatment in the form of increase in serum serum glutamic pyruvic transaminase, corticosteroids, methotrexate, cyclosporine, etretinate and serum glutamic-oxaloacetic transaminase and alkaline other immunomodulators as well as hydroxyurea. Photo- phosphatase activities and considerably reduced the chemotherapy and alternative medicine have been also histopathological alterations. Further, triterpene fraction extensively used for health care and are supporting to be a reduced thiopentone-induced sleeping time, suggesting new era of medication. There are increasing research efforts the protection of liver metabolizing enzymes. The authors to develop herbal formulations to treat psoriasis. Clinic claim triterpenes administration changed the tissue redox and histopathlogical evaluation of ointment formulation system by scavenging the free radicals and by improving W. tinctoria Cocos nucifera prepared from and (RegSoR) the antioxidant status of the liver replenished the depleted suggests superior efficacy of herbal formulation with a hepatic glutathione and superoxide dismutase. Triterpene best result of formation of the granular layer and marked pretreatment improves bromsulphalein clearance of disappearance of the spongiform pustules, dermal vessel the CCl4-intoxicated liver and increases the cellular tortuosity and normalization. The reduction of the dermal viability. These effects substantiate protection of cellular infiltrates observed with herbal treatment. The formulation phospholipid from peroxidative damage induced by is found to be safe and non-toxic to liver, kidney, and highly reactive toxic intermediate radicals formed during W. tinctoria haemopoietic system[118]. Emulsion of showed biotransformation of CCl4. Triterpene fraction afforded reversal of parakeratosis to orthokeratosis in mouse-tail test protection against the hepatic abnormalities due to the β with enhanced hyperplasia and diminished parakeratotic presence of lupeol and -amyrin. The study supports the W. tinctoria scales with tendency for separation forming healthy layer traditional use of bark in treatment of liver et al beneath the response that matches with standard method diseases. Sathianarayanan . investigated diuretic of treatment of retinoids[15,119,120]. United States Patent (No. activity on male albino rats using water and alcoholic Mahendra S. Khyade and Nityanand P. Vaikos/Journal of Coastal Life Medicine 2014; 2(10): 826-840 834 W. tinctoria extract of leaves of [124]. The extracts showed anticonvulsant activity of test drug with LD50 determined a potent diuretic effect with increase in electrolyte to 891.25 mg/kg in the mice. These results indicate that concentration in urine, when compared to standard drug the drug has central depressant, muscular relaxant and et al (frusemide) in albino rats[124]. anticonvulsant activity[128]. Murugnandan . also studied W. tinctoria Antidiarrheal potential of ethanol bark extract and anxiolytic and antidepressant effect of leaves W. tinctoria isolated steroidal alkaloid fraction of was on brain monoamines and metabolites in rats[129]. In another et al investigated on different experimentally induced diarrhea interesting study, Selvam . have attempted antiviral W. tinctoria models of rats, isolated rat ileum, and on enteric bacterium. activity and cytotoxicity of [130]. Different The extract at 500 and 1 000 mg/kg dose, and steroidal extracts of leaves selected against replication of HIV-1 (IIIB) alkaloid fraction at dose 50 and 100 mg/kg, significantly in MT-4 cells and hepatitis C virus in Hue 5.2 cells. The inhibited the frequency and wetness of faecal droppings in cytotoxicity of leaves also tested against mock-infected castor oil-induced diarrhea. Further, extract and steroidal MT-4 cells and Hue 5.2 cells. These extracts of the leaves alkaloid fraction decreased propulsion of charcoal meal have been evaluated for anti HIV-activity and cytotoxicity and reduced prostaglandin E2-induced enteropooling. against HIV-1 (IIIB) replication in acutely infected MT-4 Steroidal alkaloid fraction reduced amplitude, frequency, cells. None of the extracts exhibited anti-HIV activity and tone of spontaneous gut movement; also inhibited in acutely infected MT-4 cells. However, the chloroform acetylcholine-induced contraction of rat ileum. The extract exhibited a maximum protection at 48% of the MT-4 results of this study confirmed good antidiarrheal activity cells against the cytopathic effect of HIV-1 (IIIB) at subtoxic W. tinctoria of against secretory, osmotic, motility related, concentration. The anti-hepatitis activity revealed that 50% and inflammatory diarrhea[125]. The bark extract plays effective concentration for the inhibition of hepatitis C virus an important role in infertility. The ethanol extract and subgenomic replicon replication in Huh 5.2 cells (luciferase µ its hexane-soluble, chloroform-soluble, water-soluble assay) by chloroform extract was 10 g/mL, whereas ether W. tinctoria and water-insoluble fractions of the bark of and ethanol extracts inhibits hepatitis C virus RNA synthesis µ when administered orally during pre-implantation, peri- at the concentration (EC50) of 23 and 29 g/mL, respectively. implantation and early post implanation in adult female The concentration of extracts reduced the growth of of Sprague-Dawley rats showed anti-implantation effect exponentially proliferating Huh 5.2 cells by 50% was greater µ with moderate to potent estrogen-agonistic activity at 250 than 50 g/mL[130]. mg/kg dose; indicating antifertlity activity of extract[126]. However, authors suggested that further studies on clinical 6. Toxicological assessment and isolation of active natural products for development of newer agent from natural origin are required to identify contraceptive agents from natural sources lacking potent Lakshmi and Divakar screened the toxicological profiles et al W. tinctoria estrogenic activity. Kumar . evaluated the reducing of leaves of by employing brine shrimp assay Artemia salina power and free radical scavenging activity of ethanol extract method ( Leach) using seven different W. tinctoria In vitro of bark[127]. antioxidant evaluation was leaves to extract, namely ethanol (70%) methanol, water, done by measuring the reducing power and inhibition of petroleum ether, dichloromethane, ethyl acetate and superoxide production. The study demonstrates that the chloroform[131]. Among the seven different solvent leaf W. tinctoria ethanol bark extract has significant antioxidant and free extracts of , the ethanolic (70%) and methanolic µ radical scavenging activity[127]. leaf extracts showed an LC50 of 471.604 g/mL and 517.038 µ Moreover, neuropharmacological potential of seeds g/mL. The other remaining solvent extracts taken from the W. tinctoria of has also been studied[128]. 50% alcoholic leaves showed no toxicity in brine shrimp assay method. extract when studied for central action on mice, the drug The percentage mortality LC50 was also calculated by diminished the alertness, grooming and spontaneous constructing graphs considering log concentration versus locomotory activity and pain response in gross behavioral percentage mortality. However, after 24 h, all the samples studies. Analgesiometer test using hot wire for providing showed a significant lethality but these were not accepted thermal stimulus in the rats showed significant analgesia for safer and more accurate result. Because after 24 h, in all the doses studied (150, 200, and 300 mg/kg, body some nauplii may die normally as their life span is 24-48 weight). The higher dose of 200 and 300 mg/kg showed h. The toxicity that was found in the other vials of different significant supramaximal electroshock seizure indicating concentrations might be due to the toxic property of the Mahendra S. Khyade and Nityanand P. Vaikos/Journal of Coastal Life Medicine 2014; 2(10): 826-840 835 W. tinctoria plant extracts. may contain some cytotoxic prospects of isolating and using EPIs clinically from leaves W. tinctoria constituents that may be soluble in methanol and (70%) of , since a compound indirubin from the In vivo S. ethanol than other solvents used. safety and efficacy leaves of this species has shown such activities against W. tinctoria aureus of bark extracts of at dose 1 000 mg/kg have [88]. The extracts obtained from different organs in also been studied on some haematological, histological, above mentioned pharmacological studies using various biochemical and antioxidant enzyme status of rat liver and solvents have been evaluated for multi-effective property W. tinctoria kidney[132]. of the plant . It is worth to isolate some pure phytopharmaceuticals which in turn can be used as lead molecules for synthesizing novel agent having good 7. Conclusion therapeutic value. A critical analysis of the present study indicates the W. Biologically active compounds from the natural sources fact that although the number of diseases, for which tinctoria have attracted the scientists working on the health acts as a medicine in one or other way are large, W. tinctoria W. problems. is one of the plants, with a great yet, in view of the wide range of medicinal uses of tinctoria medicinal potential claimed to contain the varieties of mentioned in ethnobotanical survey, Ayurveda, phytochemicals, which play an important role in one or Siddha, Unani system and otherwise, it is mandatory that other ways in different biological activities. The traditional more clinical and pharmacological studies should be application of leaves in human beings for the treatment conducted to investigate the unexploited potential of the of jaundice and recent study performed on human cell plant. Furthermore, with regard to the development of line (Huh 5-2) evidenced the antihepatitis viral property quality herbal medicine, the standardization of extracts, of leaf extracts[130] validates its traditional claim against phytopharmacology of different extracts, isolation and jaundice. However, the findings obtained on concentrating characterization of active phytopharmaceuticals, elucidation W. tinctoria the activity of extract requires further detailed of mechanism of action of the isolated compound as well as investigation. Various poly-herbal formulations containing clinical trials of the compounds are much needed. W. tinctoria W. tinctoria are available in the markets for psoriasis, represents a most valuable medicinal plant diarrhea, dysentery, dandruff and for rejuvenation of sheltering a variety of the important chemoconstituents W. tinctoria joint function. It is the leaf extract of which which confer most of the characteristics of the plants. Based forms the major constituent in the Siddha preparation for on the facts, it is concluded that this plant species may the treatment of psoriasis. The experimental evidence of form a good potential source in the drug development. antimicrobial property has been produced in the laboratory against the skin microorganism supports the claims of the Conflict of interest statement plants used in the cure of psoriasis in the Siddha system[85]. In vitro studies on the extracts from this species have shown a range of antimicrobial activities. However, in some We declare that we have no conflict of interest. studies the type of inhibitory activity, the concentrations of inhibition, the method used for screening and positive Acknowledgements controls are not well defined. This suggests that there is a need for some of these to be re-evaluated using accepted research methods. Thanks to the Head Department of Botany, Dr. Babasaheb There is an increased interest in the search of plant Ambedkar Marathwada University, Aurangabad for all compounds that may inhibit the bacterial efflux pump, laboratory facilities (financially supported by University since efflux is a common resistance mechanism employed Grants Commission, New Delhi). We are also thankful to Dr. by bacteria. An effective EPI could have significant Deepak M. Kasote, Department of Pharmaceutical Sciences, benefits, including restoration of antibiotic sensitivity Tshwane University of Technology, Pretoria, South Africa, in a resistant strain bacteria and a reduction in the dose for his thorough revision of this review and providing us of antibiotic required for inhibition, possibly reducing with his invaluable suggestions. One of authors, MSK, adverse drug effects[133,134]. Another significant role of sincerely thanks to the Principal, S. N. Arts, D. J. Malpani EPI is that when used with an antibiotic it delays the Commerce and B. N. Sarda Science College, Sangamner for emergence of resistance to that antibiotic[135]. There are help and encouragement. Mahendra S. Khyade and Nityanand P. Vaikos/Journal of Coastal Life Medicine 2014; 2(10): 826-840 836 Comments immunomodulator, anti-inflammatory, analgesic and anthelmintic activities together with the wound healing Background property, besides its traditional uses. A clinical study W. tinctoria belonging to family Apocynaceae, is an further suggests that the plant has broad range of important medicinal plant used by indigenous communities applications in the treatment of psoriasis and other skin in India. Different parts of this plant such as stem bark, diseases. leaf, seed and root are known to have medicinal properties. Innovations and breakthroughs The medicinal value of this plant for the treatment of a large number of human ailments is mentioned in The authors collected the pertinent data from the entire Ayurveda, Siddha, Unani (codified drug system) and folk world, where the plant species is distributed; moreover medicine (non codified drug system). In the last more the authors shared their own contribution in the form of than three decades, several studies have been carried out research on pharmacognosy and antimicrobial activity. The on this medicinal plant to facilitate evidence in favor of lacunae left in the research can be a future perspective in its traditional uses. The authors wanted to discuss future the field of phytochemistry and pharmacology. research opportunities through the present review in the Applications form of its comprehensive information on the traditional uses, ethnopharmacology, phytochemistry, pharmacological Such type of review provided comprehensive information research and toxicology. to industry, research organization and institutes as well as beginners in the field of phyto pharmacology research. Research frontiers Peer review The voluminous data on traditional uses, ethnopharmacology, phytochemistry, pharmacological research and toxicology The present review provides comprehensive information can be a foundation for future research opportunities. The on the traditional uses, ethnopharmacology, pharmacognosy, root of this plant is less studied organ and consists of many phytochemistry, biological activities, pharmacological W. tinctoria phytochemical constituents. Moreover, many traditional activities and toxicology of . The data provided uses of this plant are still not substantiated or validated by in the present manuscript is worthy and written in good in vivo in vitro studying and methods. So further study in this format of the journal. regard can be available for future studies.

Related reports References

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