Author’s Accepted Manuscript A comprehensive analysis on Symplocos racemosa Roxb.: Traditional uses, botany, phytochemistry and pharmacological activities Niyati Acharya, Sanjeev Acharya, Unnati Shah, Ripal Shah, Lal Hingorani www.elsevier.com/locate/jep PII: DOI: Reference: S0378-8741(16)30042-3 http://dx.doi.org/10.1016/j.jep.2016.01.043 JEP9954 To appear in: Journal of Ethnopharmacology Received date: 1 August 2015 Revised date: 30 January 2016 Accepted date: 31 January 2016 Cite this article as: Niyati Acharya, Sanjeev Acharya, Unnati Shah, Ripal Shah and Lal Hingorani, A comprehensive analysis on Symplocos racemosa Roxb.: Traditional uses, botany, phytochemistry and pharmacological activities, Journal of Ethnopharmacology, http://dx.doi.org/10.1016/j.jep.2016.01.043 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A comprehensive analysis on Symplocos racemosa Roxb. : Traditional uses, botany, phytochemistry and pharmacological activities Niyati Acharyaa*, Sanjeev Acharyaa, Unnati Shahb, Ripal Shahc, Lal Hingoranid a Department of Pharmacognosy, Institute of Pharmacy, Nirma University, Ahmedabad382481. b Department of Pharmacognosy, Pioneer Pharmacy Degree College, Vadodara-390019. c Sun Pharma Advanced Research Center, Tandalja, Vadodara-390012. d Pharmanza Herbal Pvt. Ltd., At post. Kaniya, Dist. Anand-388430. *Corresponding author Dr. Niyati S. Acharya Assistant Professor, Department of Pharmacognosy Institute of Pharmacy, Nirma University, Sarkhej Ahmedabad Highway Ahmedabad-382481, Gujarat, India Tel.: +91- 9824513258 Fax No.: 02717- 241916 E-mail: niyati20103@gmail.com, niyati.acharya@nirmauni.ac.in ABSTRACT Ethanopharmacological relevance: Symplocos racemosa Roxb. belongs to a unigeneric family Symplocaceae, known as lodhra in Sanskrit; is a small evergreen tree, found throughout the tropical and sub-tropical countries. Ethnobotanical literature indicates use of S. racemosa in treatment of eye disease, skin diseases, ear diseases, liver and bowel complaints, tumors, uterine disorders, spongy and bleeding gums, asthma, fever, snake-bite, gonorrhea and arthritis. The main aim of this review is to provide detailed phytopharmacological profile on S. racemosa in support with the traditional practices and ethnomedicinal uses. Materials & methods: All relevant worldwide accepted databases have been searched for the name “Symplocos racemosa” along with other literature from Indian Classical texts and Pharmacopoeias. The accessible literatures available on S. racemosa, were collected through electronic search on Pub med, Scopus, Science direct and traditional reports. Results: S. racemosa is important Indian traditional drug used in many Ayurvedic and herbal formulations for treatment of liver as well as uterine disorders and leucorrhoea. Majority of phytopharmacological reports are on stem bark of the plant which include anti-cancer, hepatoprotective, anti-oxidant, anti-androgenic effect, anti-inflammatory, wound healing activity and anti-diabetic effects. Phytochemical studies indicated presence of many phenolic glycosides like symplocoside, triterpenoids like betulinic acid, acetyloleanolic acid and oleanolic acid and flavonoids like quercetin which might have contributed to the observed protective effects. Conclusion: Many ethno botanical claims have been confirmed through systematic in-vitro and in-vivo pharmacological studies on different extracts of stem bark and isolated constituents. However, systematic studies on the bio-markers are desirable to establish mode of action and to validate the traditional claim in clinical practice after proper safety assessment. The conservation data of genus Symplocos showed risk of extinction due to restricted distribution in the wild hence systematic techniques should be developed for the maintenance of this plant. Keywords: Symplocos racemosa, Lodhra, Traditional uses, Phenolic glycoside, Pharmacological activities Chemical constituents with pubchem ID        Oleanolic acid: pubchem/10494 Ellagic acid: pubchem /16212384 Betulinic acid: cid: 64971 Beta-amyrin: pubchem/73145 Beta sitosterol: pubchem/122544 Salireposide: cid: 117440 Acetyloleonolic acid : cid: 151202 Graphical Abstract: 1. Introduction Symplocaceae is a unigeneric family consisting of only one genus named Symplocos; distributed in tropical and subtropical Asia, Malaysia and America. Symplocos is a genus of flowering plants in the order Ericales, containing almost 318 species, about 25 species are found to be dioecious, of which only few are of economic importance (Aranha Filho et al., 2009; Hegnauer, 1973). The genus has been found to contain many chemicals such as flavonoids (Tschesche et al., 1980; Tanaka et al., 1980, 1982; Lin et al., 1996), iridoids (Iida et al., 1990), lignans (Ishida et al., 2001), steroids (Frotan et al., 1983), triterpenoids (Ali et al., 1990), alkaloids (loturine, loturidine and colloturine) and red coloring matter (Ayurvedic Pharmacopoeia of India, 2001). The genus has been traditionally reported in the treatment of bacterial diseases (Khan, 2001), diarrhea and dysentery, eye diseases, hemorrhagic gingivitis, menorrhagia, uterine disorders (Ali et al., 1990), bowel complaints, ulcers (Dhaon et al., 1989), malaria, enteritis and snake bite (Li and Yu, 2003). It has been gaining popularity in recent times due to its diverse biological activities, particularly gynecological and digestive disorders along with antitumor and phosphodiesterase inhibitory activities (Huo et al., 2007). The species of genus Symplocos, having the biological utility and economic importance are Symplocos racemosa Roxb., S. caudata Wall. ex G. Don (S. sumuntia Buch.-Ham. ex D. Don), S. celastrinea Mart. ex Miq., S. chinensis (Lour.) Druce (S. paniculata (Thunb.) Miq.), S. glauca (Thunb.) Koidz., S. confusa Brand, S. glomerata King ex C.B. Clarke, S. lancifolia Siebold & Zucc., S. lucida (Thunb.) Siebold & Zucc., S. microcalyx Hayata, S. spicata Roxb., S. tinctoria (L.) L’Her., S. uniflora (Pohl) Benth. and S. vacciniifolia H.S. Chen & H.G. Ye (Badoni et al., 2010). S. martinicensis Jacq., S. gardeneriana Wight, S. anomala Brand, S. wikstroemiifolia Hayata, S. euryoides Hand.-Mazz., S. ovatilobata Noot., S. groffii Merr., S. fordii Hance, S. nokoensis (Hayata) Kaneh., S. hainanensis Merr. & Chun ex H.L. Li, S. heishanensis Hayata, S. ramosissima Wall. ex G. Don, S. atriolavicea Merr. & Chun ex H.L. Li, S. viridissima Brand, S. pseudobarberina Gontsch., S. adenophylla Wall. ex G. Don, S. xylopyrena C.Y. Wu & Y.F. Wu, S. modesta Brand, S. dryophila C.B. Clarke, S. crassilimba Merr., S. hookeri C.B. Clarke, S. pilosa Rehder, S. pyrifolia Wall. ex G. Don, S. sulcata Kurz, S. cochinchinensis (Lour.) S. Moore, S. paucinervia Noot., S. glandulifera Brand, S. adenopus Hance, S. stellaris Brand, S. dolichotricha Merr., S. ulotricha Ling, S. fukienensis Ling, S. austrosinensis Hand.-Mazz., S. congesta Benth, S. poilanei Guill, S. pendula Wight and S. spectabilis Brand are the other species mentioned in the text of Flora of China (Shan fan S., 1996). Symplocos racemosa is a small evergreen tree found commonly in the plains and hills of northern India and other Asian countries, up to an altitude of 1400 m. S. racemosa is known commonly as Symplocos bark in English; Lodha in Hindi (means glorious and the one which is used in opthalmia); Lodhra in Sanskrit, rodhra, lodhrah, lodhraka, sabara, pittaka in Tamil; tirita, vellilathi, vellilothram, Kaccacankai in Malayalam; pachotti in Assamese; mugam in Telugu; sapara, lodhuga in Kannada; balaloddi, shaabara mara in Urdu. (Kirtikar and Basu, 1975). The common biological synonyms of S. racemosa are S. intermedia Brand, S. intermedia Var. trichantha Hand.-Mazz., S. macrostachya Brand, S. macrostachya Brand and S. propinqua Hance. (http://www.plantlist.org) Figure 1: Symplocos racemosa: Plant and stem bark The plant contains many phytochemicals with various activities indicated in traditional system of medicines like Ayurveda and Unani. Bark has been described as an emmenogogue tonic for the persons of plethoric constitution and decoction is used as a gargle for giving firmness to bleeding and spongy gums. It also cures "Kapha" biliousness, diseases of the blood, inflammations, vaginal discharges, leprosy, elephantiasis, filaria and useful in cancers, abortions, miscarriages and vaginal ulcers (Karkar et al., 1969; Joshi, 2000; Rao et al., 2011). In Sanskrit, it is known as Lodhra which means “Propitious” or ‘Tilaka’ because it is used in making tilaka mark (bindi) on the forehead might be due to the presence of red coloring matter (Somanath, 2011). In Europe, it was formerly looked upon as a substitute for cinchona bark and has been known at various times as ‘Ecorce de latour’, ‘China nova’, ‘China californica’, ‘China brasilensis’ and ‘China paraguatan’ known as lotur bark (Watt, 1972). Some other varieties like S. createagoides Buch-Ham and S. cochinchinensis (Lour.) S. Moore were also used as the source for S. racemosa Roxb. Similarly species like S. laurina (Retz.) Wall ex G. Don, S. paniculata (Thunb.) Miq. and S. sumuntia Buch.-Ham. ex D. Don are sold in the market under the name S. racemosa (Joshi et al., 2011). A number of phytopharmacological studies are being reported on this plant S. racemosa in order to provide scientific support to various traditional uses. Majority of the reports indicated usefulness of the stem bark for the treatment of gynecological disorders, fever, inflammation and liver disorders. Several flavanol glucosides like symplocoside, symposide, leucopelargonidine-3 glucoside, ellagic acid, rhamnetin 3-digalactoside, triterpenoids like 19 α-hydroxyasiatic acid-3, 28-O-bis-β-glucopyranosides, betulin, linoleic acid, β-sitosterol and α-amyrin (Badoni et al., 2010; Nagore et al., 2012) and alkaloids like loturine, loturidine, colloturine and harmine (De Silva et al., 1979; Ishida et al., 2001) have been ascribed as chief bioactives from the plant. Traditional literature indicated that total 32 formulations contain S. racemosa bark as one of the major ingredients as mentioned in Ayurvedic Pharmacopoeia of India, 2001, for the treatment of various ailments. The coloring matter obtained from bark has been used for producing a yellow colored dye for dyeing cloths (Gaur, 1999; Kumar, 2007; Chandra Prakash Kala, 2009). The current review discuss existing knowledge on botany, traditional uses, phytopharmacology and toxicology of S. racemosa in order to highlight current research trends to fill the gaps for further future potential applications. 2. Botanical description Symplocos is a genus of flowering plants distributed in tropical and subtropical Asia, Malaysia, and America (Hegnauer, 1973). The leaves of S. racemosa are simple, glabrous, oblanceolate to narrow elliptic in shape and about 6.5-12.5 cm in length and 3-4.3 cm in width. Leaves are alternate, spiral, with narrowly acuminate apex, serrate margin and slightly recurved, canaliculated midrib with 6-12 pairs of secondary nerves. The base of leaf is acute to attenuate; having petiole up to 1.5 cm long. Bark is pale yellow to dark grey shortly fibrous, finely mottled with pale orange brown and rough. Blaze is about 7.5-13 mm in size and it occurs in channeled or curved pieces, few flat pieces also occur in thickness up to 1cm. Outer surface is uneven and rough due to fissures and cracks. The color is grayish brown to grey externally and pale to whitish-brown internally, taste is astringent and feebly bitter. Fracture is short and granular in cortical region and somewhat fibrous in inner region. The fruits are of drupe type, ellipsoid or oblong in shape, 1.5 cm long with seeds of about 1-2 cm (Ayurvedic Pharmacopoeia of India, 2001). Transverse section of mature bark of S. racemosa shows a wide thin-walled cork with rectangular cells arranged in radial rows followed by 1-3 layers of cork cambium. Secondary cortex consists of thin walled, oval and tangentially elongated parenchymatous cells towards outer side and rounded cells towards inner side with a number of stone cells, in singles or in groups scattered throughout the region having highly thickened walls with distinct pits. Prismatic and cluster crystals of calcium oxalate and simple starch grains are found to be present in a number of cortical cells. Secondary phloem is wide and consisting of sieve elements, phloem parenchyma, phloem fibres and groups of stone cells as rounded patches, thin walled oval to rectangular phloem parenchyma containing prismatic crystals of calcium oxalate. Phloem fibers are lignified with some of the isolated spindle shaped fibres with pointed ends and uni to multiseriate medullary rays consisting of rectangular cells with brown coloring matter in some cells are also present (Ayurvedic Pharmacopoeia of India, 2001). 3. Geographical distribution S. racemosa is a small evergreen tree, up to 6-8.5 m height found in the plains and lower hills throughout the North and East India, ascending in the Himalayas up to an elevation of 1400 m, Bengal, Assam and Chhota Nagpur (Sharma et al., 2000, Kirtikar and Basu, 1975). The conservation data of genus Symplocos showed that S. racemosa is vulnerable but facing the high risk of extinction in the wild; whereas S. cochinchinensis (Lour.) S. Moore was found to be near threatened medicinal plant to Karnataka and endemic plant to Western Ghats. In Pakistan only two species are found, namely S. racemosa and S. cochinchinensis (Lour.) S. Moore (Karnat, 2005). S. racemosa has been found critically endangered due to limited distribution and so highest priority has been given to conservation of this plant in Orissa as bark is recorded with high volume trade in the national level study (Envis newsletters on medicinal plants). 4. Traditional and ethno medicinal uses Ayurvedic properties reported for the barks of S. racemosa are: Taste: astringent; properties: light; potency: cool; transformation with digestion: pungent; use: good for eyes, stimulates appetite, helps in digestion and used in cough and acidity. Siddha properties reported for the barks of S. racemosa are: name: Vellilatthi, Velliloththiram, Thillakam; Taste: astringent, sweet, pharmacological action: refrigerant, antidote; uses: In ascites and bone disorders (Ayurvedic Pharmacopoeia of India, 2001). In Ayurveda, the stem bark of S. racemosa is incorporated in various formulations used for the diseases of the uterus, menorrhagia and leucorrhoea and to check abortion as well (Bhutani, 2005). The bark is boiled in water up to a gelatinous mass, and applied to treat micro fracture or dislocated bone (Manandhar, 1995). The flowering parts of S. racemosa are used against snakebite and also known for producing a yellow dye (Peter, 1993; Gaur, 1999; Kumar, 2007; Chandra Prakash Kala, 2009). In Ayurveda “Pittaja arbuda” type of tumors (tumors in small intestine and solar plexus) are reported to be treated with the bark of S. racemosa in combination with some other species like Ficus glomerata Roxb. (Moraceae), Tectona grandis L.f. (Lamiaceae), Elephantopus scaber L. (Daisy), Aglaia roxburghiana (Wight & Arn.) (Meliaceae), Caesalpinia sappan L. (Fabaceae), Terminalia arjuna (Roxb. ex DC.) Wight & Arn. (Combretaceae), Xanthium strumarium L. (Asteraceae) (Dash, 1987). “Medoja arbuda” tumors (fatty tissue tumors) also has a mention with S. racemosa, Curcuma domestica Valeton (Zingiberaceae), Triticum sativum Lam. (Poaceae) to be used in the powdered form and applied externally by mixing them with honey (Singhal, 1982). The powder of S. racemosa combined with Curcuma domestica Valeton (Zingiberaceae) and Soymida febrifuga (Roxb.) A. Juss. (Meliaceae) mixed with honey is used as an external remedy for the tumors (Murthy, 2001). Bark is mild astringent, expectorant, antiinflammatory, antifibrinolytic, febrifuge, hemostatic, emmenogogue, aphrodisiac, stomachic, constipating and supportive (Joshi, 2000, Pandey, 2011, Somanath, 2011, Singh et al., 2015). A decoction of the bark or wood is used as a gargle for giving firmness to spongy and bleeding gums and relaxed uvula (Nadkarni, 2002). The paste of bark in combination with coriander (Coriandrum sativum L. (Umbelliferae)) and sweet flag (Acorus calamus L. (Araceae)) is used for the treatment of acne and for increasing the attractiveness of the face in combination with red sander (Pterocarpus santalinus L. (Leguminosae)), Indian madder (Rubia cordifolia L. (Rubiaceae)), costus (Saussurea costus (Falc.) Lipsch. (Compositae)), beautyberry (Callicarpa americana L., (Lamiaceae)), banyan buds (Ficus benghalensis L. (Moraceae)) and lentils (Vigna mungo (L.) Hepper (Leguminosae)). The bark after heating with cow’s urine is used in combination with barley (Hordeum vulgare L. (Poaceae)), white dammar (Vateria indica L. (Dipterocarpaceae)), vetiver (Chrysopogan zizanioides (Poaceae), Reference in Flora of China), sandal wood (Santalum album L. (Santalaceae)) along with honey, butter and jaggery for increasing the attractiveness of the facial skin and in the treatment of acne (Jayalakshmi, 2011). Ethno botanical literature indicates effectiveness of bark of S. racemosa in the treatment of eye, ear, skin and gums diseases. It is also reportedly used in liver and bowel complaints, tumors, dropsy, asthma, bronchitis, fever, ulcers, nephritis, scorpion-string, snake-bite, elephantiasis, fillaria, hemorrhage, menorrhagia, leucorrhoea, hemorrhoids, gonorrhea and arthritis (Kirtikar and Basu, 1975; Raghunathan and Mitra, 2000; Nadkarni, 2002). Table 1 describes different ethnomedicinal uses of various plant parts with widely held reports advocating use of stem bark for many ailments. Table 1: Summary on ethno medicinal claims on S. racemosa Part Country/ State Local /District name Method of preparatio n Decoction, Chew Route of admin Oral (Gargle) Reference Stem bark Odisha (Sundargarh, mayurbhanj, Angur, Balangir) Lodh (Odiya) West Bengal (Purulia) Lodh Decoction with longpepper paste(3:1) --- Once a day Chakraburtty & Bhattachargee, 2006 Chhattisgarh Lodh Dye, Medicine --- Bleeding gums, Stomatitis Wound healing --- --- Chandra Prakash Kala, 2009 Ganesan, 2008 Tamilnadu Vellilethi Southern India --- --- --- Jharkhand(Mun da) Uttarpradesh (Lucknow) Nepal (Jajarkot dist.) Ludam ba Lodhra Paralysis --- --- Paste Decoction External (Thrice) - Lodh Conjunctivi tis Microfracture or dislocated bone Diarrhea Orissa --- --- Northeast India Lodhra Diarrhea --- --- Leaves Jharkhand Ludam ba Decoction Oral Seed West Bengal (Rajbanshi) Lodh Pelvic pain after child birth Diabetes Mixture (rice bear) Madhya Pradesh Lodhra Preparation of Khumra (Umbrella) --- Orally (7-10 days) --- Entire plant --- Ethnomedicinal use Gum & teeth infection (infection by CBL:34233 ); For Hard adherent teeth Abortion Singh et al., 2013 Ignasimuthu and Ayyanar, 2009 Kumar and Abbas, 2012 Shankar & Ali, 2014 Manandhar,199 5 Dash and Padhy, 2006 Laloo and Hemlalatha, 2011 Bisnoi et al, 2012 Mukherjee & Mitra, 2011 Shodhganga database Various Ayurvedic formulations containing S. racemosa are available in Indian market and used in throat and tooth disorders, skin problems, abdominal diseases, gynecological and uterine disorders (Ayurvedic formulary of India, 2000; Sekar and Mariappan, 2008). Lodharasava, one of the most common fermented liquid dosage form containing S. racemosa has been mentioned in various treatises for the management of Shvitra (vitiligo) and Madhumeha (diabetes mellitus) as one of the common medicines (Singh and Jana, 2013). Likewise other marketed Ayurvedic formulations containing S. racemosa are summarized in Table 2 with classical Sanskrit name of the formula, dose, composition of stem bark calculated on the total percentage basis (0.038-16.66%) and Ayurvedic uses along with common description. Table 2: Ayurvedic formulations containing stem bark of S. racemosa Formulation* Dose Composition Ayurvedic uses of stem bark (%) Srikhandasava 12-24mL 24g (0.055) Panatyaya (alcoholism), Pana (panchkarma) Pippalyadyasava 12-24mL 24g (0.038) Arsa (piles), Grahani (sprue), Gulma (gastritis), Pliha (spleen disorder), Udara (abdominal disease), Karsya (weight loss), Ksaya (tuberculosis), Pandu (anemia) Usirasava 12-24mL 48g (0.139) Prameh (diabetes), Raktapitta (leprosy), Krmi (worm infestation), Kustha (psoriasis), Arsa (piles), Sotha (edema) Kumaryasava 12-24mL 24g (0.115) Agnimandya (indigestion), Pattisula (duodenal ulcer), Parinamasula (ulcerative colitis), Udavartta (belching), Mutrakrcchra (dysuria), Prameh (diabetes), Raktapitta (leprosy), Asmari (renal calculi), Apasmara (epilepsy), Krmi (worm infestation), Sukradosa (morbid affection of semen genital), Smrtiksaya (memory loss), Daurbalya (general debility), Udara (abdominal disease), Karsya (underweight), Ksaya (weight loss/tuberculosis), Aruci (anorexia), Vaivarnya (skin discoloration) Candanasava 12-24mL 48g (0.146) Karsya (underweight), Ksaya (weight loss), Mutrakrcchra (dysuria), Sukrameha (spermatorrhea), Hrdroga (heart disease), Balaksaya (weakness), Agnimandya (indigestion) Dasamularista 12-24mL 960g (1.158) Aruci (anorexia), Chardi (vomiting); Grahani (sprue), Gulma (epigastricpain), Kasa (dry cough), Svasa (dyspnea), Ksaya (weight loss/tuberculosis), Dhatuksaya (general debility), Vatavyadhi (arthritis), Arsa (piles), Bhagandara (fistuala), Pandu (anemia), kamala (jaundice), Kustha (psoriasis), Meha (diebetes), Mutrakrcchra (dysuria), Karsya (underweight), Sukraksaya (oligospermia), Vandhyatwa (infertility), Daurbaly (general debility), Agnimandya (indigestion); Udara (abdominal disease), Sarkara (calculi) Rodhrasava 12-24mL 12g (0.24) Meha (diabetes), Aruchi (anorexia), Grahani (sprue), Pandu (anemia), Arsa (piles), Kustha (psoriasis), Krmi (worm infestation), Sthaulya (Obesity), Svitra (Leucorrhoea), Garbhasayaroga (uterine disorders) Sarivadyasava 12-24mL 192g (0.41) Vatarakta (gout), Meha/ Parmeha (diabetes), Upadamsa (genital disorder), Bhagandara (fistula), Raktavikara (as blood purifier), Daurbalya (general debility), Agnimandya (indigestion) Draksadi 48g 1part (5.88) Kwathchurna Jvara (fever), Chardi (vomiting), Raktapitta (leprosy), Madatyaya (alcoholism), Pipasa (thirst), Kamala (jaundice), Bhrama (vertigo), Murccha (temporarily loss of consciousness), Srama (restlessness) Nyagrodhadi Kwathchurna 48g 1part (4.76) Grahani (sprue), Raktapitta (leprosy), Trishna (thirst), (obesity), Vrana (discolouration), Yoniroga (vaginal Sthaulya disorder), Ashtibhanga (bone fracture) Jivantyadi Ghrita 12g 12g (0.044) Timira (cataract) (Anupana: warm milk, water) Nyagrodhadi 13g 1part (3.57) Churna Pusyanuga Churna Mutrakrcchra (dysuria), Mutraghata, Prameha (diabetes), (Anupana: honey, triphala kasaya) 1-3g 1part (3.84) Arsa (piles), Rajodosa (menstrual disease), Yonidosa (Vaginal disease), Svetpradara (Leucorrhoea), Asrgdara (metroragea/menorrhea) (Anupana: honey, rice water) Brhatgangadhara 1-3g 1part (7.14) churna Samangadi churna Atisara (diarrhea), Pravahika (dysentery), Grahani (sprue) (Anupana: Honey, rice water) 2-4g 1part (16.66) Raktarsa (bleeding piles) (Anupma: Goat’s milk, water) Arimedadi Taila --- 12g (0.040) Kabalagraha (gargle), Nasya (nasal drop), Dantaroga (dental disorder) Mukharoga (oral disease) Kunkumadi Taila --- 12g (0.14) Nasya (nasal drop), Abhyang (massage); Mukharoga (oral disease), Varna (discoloration), Yauvanapitika (acne), Vyanga (facial melanosis), Masaka (Mole) (External) Grahanimihira 12g 12g (1.041) Taila Atisara (diarrhea), Grahani (sprue), Hikka (hiccup), Jvara (fever), Kasa (dry cough), Svasa (dyspnea), Kamala (jaundice), Prameha (diabetes), Vali Palita (loose skin & white hair), Trsna (thirst), Chardi (vomiting), Bhram (vertigo), Kostharuja (abdominal pain), Arsa (piles); Meha (diabetes), Svayathu (swelling), sula (pain), Karsya (underweight), Sukraksaya (oligospermia), Garbhasrava (miscarriage), Garbhapata (abortion) (Anupana:Butter milk, Musta Kasaya, Dhanyaka Kasaya) Jatyadi Taila --- 10.66g (0.26) Abhyanga (massage) (External) Kacchu (blisters), Sphotaka (boil/carcubcle), Nadivarna (fistula); DustaVarana (Unhealed wound), Dant-nakha ksata (dental carries, nail injury) Pramehamihira 6-12g 12g (0.11) Taila VataVyadhi (arthritis), Visama jvara (malaria); Prameha (diabetes), Medogatavata, Majjagata (muscular pain), Dhvajabhanga (weakness & dysfunction of sexual organ), Daha (burning), Pipasa (thirst), Chardi (vomiting), Mukhasosa (dryness of mouth), (Anupana: warm milk, water, honey) & Abhyanga (External use) Bhrngaraja Taila --- 48g (1.086) Kabalagraha (gargle), Nasya (nasal drop), Dantaroga (dentestry), Mukharoga (oral disease), Karnaroga (ear disease), Netraroga (eye disease), galagraha (disease of throat), Manyastambha (cervical spondolysis), Kalitya (alopecia), Indralupta (alopecia), Siroroga (disease of head), Kesapata (hair fall) Tutthadi lepa --- 1part (8.33) Upadamsaja (gonorrhea), Vrana (wound), Damsa Vrana (insect bite) (Used with honey & applied) Khadiradi Gutika 2g 12g (0.044) Mukhadaurgandhya (hellutosis/bad smell), Mukha paka (mouth ulcer), Danta roga (dental disorders), Galaroga (disease of throat), Aruci (anorexia), Caladanta (loose tooth), Asyaroga (disease of oral cavity) (Anupana: honey) Marma gutika 2g 96g (0.98) Aghata (injury), Marma vikara (disease of vital part) Vimala vartti --- 1part (11.11) Timira (cataract), Kacca (2nd stage cataract), Netra kandu (itching of eyes), Patalaroga (eye disorders) Laghugangadhara Churna 5-10g 1part (16.66) Atisara (diarrhea), Pravahika (dysentery), (Anupana: buttermilk 250mL; jaggery 1g) Asthisandhanaka --- 120g (10) Lepa Sula (pain), Sotha (swelling), Asthibhanga (bone fracture), Asthicyata (injury), Asthicyuta (bone dislocation) Nagarjunanjana --- 1part (6.6) Patalaroga (eye disorder), Timraroga (cataract) Piyusavalli rasa 500mg 6g (4.83) Atisara (Diarrhea), jvara (fever), sotha (swelling/edema), grahani (sprue), Vibandha (constipation), Aruci (anorexia), Chardi (vomiting), Gudabhramsa, Kamala(jaundice), Udararoga (abdominal disorder), Sutikaroga (post natal disease), Pandu (anemia), Prameh (diabetes), Agnidagdha (burn) (Anupana: jaggery) * Churna is a solid powdered formulations, gutika and vartii are pills/tablets, anjana is a semisolid preparation for eye application, asava and arishta are liquid fermented preparations, lepa is a semisolid preparations and ghrita and taila are oil based liquid dosage forms of Ayurveda. 5. Phytochemistry Phytochemical investigations on this plant have shown presence of many constituents. Various researchers have isolated active constituents from this plant and systematically evaluated for the several biological activities. Majority of the flavonoids and related compounds have been isolated from aerial parts of the plant while glycosides of different types have been extracted from the polar fractions of the bark of the plant. The compounds isolated from S. racemosa are documented and listed in Table 3 and their structures are displayed in Fig. 2(a) and 2(b). Figure 2 (a): Chemical constituents of S. racemosa Figure 2(b): Chemical constituents of S. racemosa Table 3: Summary on phytochemical reports of S. racemosa Extract Plant Chemical constituents Reference Betulinic acid, acetyloleanolic acid, oleanolic acid Ellagic acid De Silva et al., 1979 De Silva et al., 1979 part Petroleum ether Bark extract Cold methanolic extract Methanol extract Petroleum ether extract ethyl extract and acetate Symposide Dhaon et al., 1989 Triterpenes: 3-oxo-urs-20cr-12,18(19)-dien-28- Ali and oic acid, 24-hydroxyolean-12-en-3-one, Srivastava, betulinic acid, oleanolic acid, 28-hydroxy-20crurs-12,18(19)-dien-3/I-yl acetate 1990 Ethyl acetate soluble fraction of methanol Phenolic glycoside of salirepin series: Benzoylsalireposide, Salireposide Triterpenes & steroids: β-amyrin, oleonolic acid, β -sitosterol Ahmad et al., Phenolic glycoside: symplocomoside, symponoside, symplososide, symploveroside Abbasi et al., Phenolic glycoside: Symploconoside A&B Ahmad et al., 2003 extract Ethyl acetate soluble fraction 2004 methanol extract Ethyl acetate soluble fraction 2005 methanol extract n-butanol soluble fraction of methanol extract n-butanol fraction of methanol extract n-butanol fraction of methanol extract Ethanol (95%) Ethyl substituted glycoside: 1-ethyl brachiose- Abbasi et al., 3’-acetate, ketochaulmoogric acid, 2005 nonaeicosanol, triacontylpalmitate, methyl triacontanoate Phenolic glycoside: symplocuronic acid Ahmad et al., symplocemoside, Salirepin 2007 Benzylated glycosides: Locoracemosides A, B &C Phenolic glycoside: 3, 5 - dihydroxy - 2(hydroxyl methyl)-6-(3,4,5-trimethoxy extract phenoxy)tetrahydro-2H-pyran-4-yl 4-hydroxy3-methoxy benzoate Ethyl acetate Aerial Quercetin-3-O-α-L-rhamnopyranoside, soluble fraction parts mearnsetin-3-O-α-L-rhamnopyranoside, of methanol quercetin-3-O-β-D-(6"-O-galloyl)extract glucopyranoside, kaempferol-3-O-β-Dgalactopyranoside, quercetin-3-O-β-Dgalactopyranoside, quercetin-3-O-β-Dglucopyranoside, kaempferol-3-O-β-D-(6"-Ogalloyl)-glucopyranoside, 3'-Omethylepicatechin-7-O-β-D-glucopyranoside, 3'-O-methycatechin-7-O-β-D-glucopyranoside, quercetin-3-O-rutinoside, quercetin-3-O-(2G-βD-xylopyranosylrutinoside,(-)epiafzelechin-7O-β-D-glucopyranoside, afzelechin-4'-O-β-Dglucopyranoside, kaempferol-3-O-β-Dglucopyranoside, quercetin-3-O-(2G-β-Dxylopyranosylrutinoside, Sympracemoside 6. Pharmacological investigation Ahmad et al., 2008 Vijayabaskaran et al., 2010 Jung et al., 2015 Most remarkably, bark has been investigated more compared to other plant part for a range of pharmacological activities and we have represented the studies described on different extracts, fractions and isolated compounds from the bark. Table 4 summarizes variety of indicated biological actions with details on study models, duration and dose range tested for S. racemosa. 6.1. Anticancer activity With reference to the traditional mention of this plant, bark has been investigated by many researchers for the protective effects in various in vitro cancer models. However these findings still require a support of preclinical investigations on different bioactives of the bark for its anticancer potential. Vijayabaskaran et al. (2010) evaluated ethanolic extract of S. racemosa bark (100 and 200 mg) against Ehrlich ascites carcinoma (EAC) bearing Swiss Albino mice. The ethanolic extract exhibited potential antitumor and antioxidant activities with increased life span (21.27%) of EAC tumor bearing mice and decreased lipid peroxidation and thereby augmented the endogenous antioxidant enzymes in the liver as compared to standard drug vincristine (0.8 mg/kg). Further ethanolic extract of S. racemosa bark (6.125-100 μg/mL) showed potent cytotoxic activity against MCF7 (75 μg/mL), moderate activity against HT29 (80 μg/mL) and less activity on HepG2 (>100 μg/mL) cell line. Raval et al. (2009) have evaluated the chloroform, n-butanol and ethyl acetate extracts (0.005-100 μg/mL) of S. racemosa bark using the sodium 3´-[1-(phenylaminocarbonyl)- 3,4tetrazolium]-bis (4-methoxy-6-nitro) benzene sulfonic acid hydrate (XTT) salt based cytotoxicity assay against HL60 (Human leukemia) and HeLa (Human cervix cancer) cell line. Butanolic extract of S. racemosa bark showed potent cytotoxic activity against HL60 (27183 ng/mL) and HeLa (22861 ng/mL) cell line. Ethyl acetate extract of S. racemosa bark showed less cytotoxic activity against HL60 (117084 ng/mL), HeLa (137151 ng/mL) cell line whereas chloroform extract has not displayed any cytotoxicity against both cell lines. Assessment of antiangiogenic activity of symplocomoside and symponoside glycosides (0-5.0 mM) isolated from the bark revealed thymidine phosphorylase inhibitory activity (IC50 value 65.45±5.08 µM and 94.17±4.05 µM) associated with angiogenesis. Thymidine phosphorylase is known as the platelet-derived endothelial cell growth factor or an angiogenic factor, that catalyses the phosphorolysis of deoxythymidine to thymine and 2deoxy-D-ribose-1-phosphate. Increased angiogenesis and poor prognosis are associated with increased thymidine phosphorylase protein expression in colorectal and endometrial cancers (Hussain et al., 2009). Subbaraju et al. (2006) have evaluated the cytotoxic potential of water, alcohol and hydro-alcoholic extracts of S. racemosa (1-5000 μg/mL) using brine shrimp bio-assay (Artima salina leach) with LC50 value (lethal concentration) 90 μg/mL. 6.2. Antimicrobial activity Antimicrobial investigations on S. racemosa are focusing on importance of bark constituents and effects of one of the herbomineral formulation containing this drug on resistant bacteria. Devmurari (2010) examined antibacterial activity of petroleum ether and ethanolic extract of S. racemosa bark (100, 300, 500 and 700 μg/well) against gram positive bacteria, Staphylococcus aureus, Enterococcus faecalis, Bacillus cereus and gram negative bacteria Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli by agar well diffusion method and ciprofloxacin was used as the standard. Ethanolic extract of S. racemosa bark exhibited overall good antibacterial activity but comparatively poor activity against gram negative microorganisms like P. aeruginosa and E. coli. Further antimicrobial potential of poly-herbo mineral formulation Jatyadi taila containing S. racemosa bark as one of the ingredient has also been reviewed by Baljinder et al. (2011). Methicillin resistant staphylococcus aureus (MRSA) is well known superbug commonly responsible for wound related infections most ominously for life threatening conditions. Jatyadi taila (100 μL) has shown promising result against methicillin resistant staphylococcus aureus using in-vitro agar well diffusion method with zone of inhibition 18.53±0.21 mm and found comparable in effectiveness to gentamicin (10 μg/100μL) as a positive control as anti methicillin resistant staphylococcus aureus (MRSA) agent (Sareena and Suchitra, 2014). 6.3. Activity against skin disorders The ethanolic extract of S. racemosa bark (100 mg/mL) was evaluated for antimicrobial activity against Propioni bacterium acne and Staphylococcus epidermidis by disc diffusion and broth dilution methods (Kumar et al., 2007). Results showed that the growth of P. acne (MIC=0.685mg/mL) was strongly inhibited by ethanolic extract in disc diffusion method which was found comparable with clindamycin (10 µg/mL). The observed effects are ascribed to tri-cyclic beta-carboline alkaloid harmine, which is reported to inhibit protein biosynthesis, microtubule formation and disturb membrane fluidity (Patel et al., 2012). 6.4. Analgesic and antiinflammatory effect Evaluation of in-vivo analgesic activity of ethanolic and aqueous extract of S. racemosa bark (200 mg/kg, p.o.) in formalin induced paw licking and tail flick models and antiinflammatory activity in carrageenan induced hind paw edema model in Wistar Albino rats showed inhibitory effects of ethanolic extract in the late phase in formalin induced paw licking model; with increase in the reaction time in tail flick model and suppressed the inflammation significantly in carrageenan induced hind paw edema model when compared to the aqueous extract of S. racemosa bark which was comparable with standard drug diclofenac sodium (5 mg/kg, p.o.). The significant suppression of inflammation indicated long duration of action of the ethanolic extract of bark might be due to prostaglandin and kinin synthesis/release inhibition and antihistamine activities which might be attributed to high levels of flavonoids and phenolics (Sharma et al., 2013). 6.5. Antiarthritic activity Choudhary et al. (2004) isolated phenolic glycosides; benzoyl salireposide and salireposide from S. racemosa bark (500-25 µM/mL) and performed cytotoxicity and kinetic studies against phosphodiesterase-I enzyme obtained from snake venom and human nucleotide pyrophosphatase phosphodiesterase-I. IC50 values of both the compounds were found to be 90 μM±0.04 and 383±0.03 μM against human nucleotide pyrophosphatase phosphodiesterase-I and 171±0.02 μM and 544±0.021 μM against snake venom phosphodiesterase respectively. Both the compounds were reported as pure competitive inhibitors of both the enzymes using Lineweaver-Burk and Dixon plots with Ki values 360 and 1000 μM against human nucleotide pyrophosphatase phosphodiesterase-I and 525 and 1100 μM snake venom phosphodiesterase respectively and found to be potential candidates for the therapy of arthritis. Further both the compounds were found to be nontoxic up to concentration of 500 μM/mL indicated by viability of more than 90% cells after 3 h of incubation period. 6.6. Antipyretic activity Vijayabaskaran et al. (2010) demonstrated antipyretic activity for ethanol extract (100 and 200 mg/kg, i.p.) of S. racemosa bark in brewer’s yeast induced pyrexia in rats. A significant antipyretic effect in maintaining normal body temperature and reducing brewer’s yeast induced elevated rectal temperature in rats by the extract was found comparable with the standard antipyretic drug, paracetamol (100 mg/kg, p.o.). 6.7. Antioxidant activity The ethanolic extract of S. racemosa (100 and 300 mg/kg) leaves and flowering tops showed significant antioxidant activity by reducing the extent of lipid peroxidation, superoxide dismutase and catalase activity in Swiss Albino mice (Devmurari, 2010). The ethanolic extract of S. racemosa bark showed potent ABTS radical scavenging activity, moderate DPPH, nitric oxide and hydroxyl radical scavenging activity compared with the standard drugs ascorbic acid and rutin (Vijayabaskaran et al., 2010). Naik et al. (2014) have evaluated the antioxidant activity of the ethanolic extract of S. racemosa bark by scavenging DPPH free radicals with IC50 value of 120 μg/mL. Kumaryasava is the Ayurvedic formulation containing Kumari (Aloe vera (L.) (Liliaceae)) as a major drug and 0.115% of S. racemosa in a fermented liquid medium. Kumaryasava (100-1000 μL/mL) has been evaluated and showed the higher antioxidant activity by DPPH and hydroxyl radical scavenging activity and total reducing power assay compared with the standard drug ascorbic acid (100 μg/mL) (Manmode et al., 2012). 6.8. Hepatoprotective activity Vijayabaskaran et al. (2010) demonstrated the ethanolic extract of S. racemosa bark (100 and 200 mg/kg, p.o.) on DMBA induced hepatocellular carcinoma in rats which showed good hepatoprotective activity by significantly reducing the levels of hepatic enzymes and total bilirubin, while increasing the levels of total proteins, reduced glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) in a dose dependent manner. The ethanol extract of S. racemosa bark (250 and 500 mg/kg, p.o.) has been shown significant hepatoprotective activity on carbon tetrachloride (CCl4) induced hepatic damage in rats which showed significant dose-dependent restoration of serum enzymes, bilirubin, albumin, total proteins and antioxidant levels (Somani et al., 2011). Another study also displayed good hepatoprotective activity of S. racemosa bark (methanolic extract at 250 and 500 mg/kg, p.o.) in carbon tetrachloride (CCl4) induced liver toxicity in rats by significantly reducing the levels of hepatic enzymes and total bilirubin and increasing the levels of total proteins in a dose dependent manner which was comparable with standard drug silymarin (100 mg/kg) (Venkidesh et al., 2011). Benzoylsalireposide; a phenolic glycoside of salirepin series, from S. racemosa exhibited α-chymotrypsin inhibitory effect in concentration dependent manner. This finding support that phenolic glycosides of bark are effective as liver protective agents as αchymotrypsin like serine protease known as NS3 protease are thought to be essential for viral replication which can lead to the progressive liver injury, cirrhosis and liver cancer (Rashid et al., 2007). 6.9. Antiulcer activity Aqueous and ethanolic extract of S. racemosa bark (250 and 500 mg/kg) were checked for antiulcer activity using pylorus ligation and aspirin induced ulcer model in rats. The experiment revealed that the aqueous and ethanolic extract have significantly reduced the ulcer index in both the models as compared to standard drug lansoprazole (8mg/kg). The study supports the traditional use of the bark in management of gastro intestinal disorders and demonstrated the role of constituents like tannins, alkaloids and flavonoids in the observed antiulcerogenic activity (Gopala Krishna et al., 2013). Saifuddin et al. (2010) evaluated aqueous and ethanolic extract of mixture of S. racemosa bark and Asarum europaeum L. (Aristolochiaceae) root (250 and 500 mg/kg) for gastric antisecretory and antiulcer activity. The extract exhibited potent antisecretory effects by decreasing pepsin secretion, gastric juice volume and acid output and showed antiulcer effects in pylorus ligated, aspirin and ethanol induced ulcer models as compared to standard drug lansoprazole (8 mg/kg). It showed significant gastro protective effects on the stomach wall in aspirin and ethanol treated rats by increasing the gastric wall mucous. The activity might be credited to the presence of flavonoids and tannins in the mixture of extracts, though there is a scope for the evaluation of protective effects at lower dose levels of the extracts and possible synergistic behavior of constituents of S. racemosa and Asarum europaeum L. (Aristolochiaceae). 6.10. Anthelmintic activity Rao et al. (2011) evaluated the anthelmintic activity of petroleum ether, chloroform and ethanolic extract (20 mg/mL) of S. racemosa bark compared to reference standard drugs piperazine citrate (15 mg/mL) and albendazole (10 mg/mL) on adult Indian earth worms, P. posthuma. Investigation revealed that the ethanol extract was endowed with potent anthelmintic activity as compared to other extracts. 6.11. Antiandrogenic effect and activity against the female disorders Antiandrogenic effect of S. racemosa bark (250, 500 and 1000 mg/kg) has been indicated in letrozole induced polycystic ovary syndrome (PCOS) in rats; (Jadhav et al., 2013) as observed by significantly decreased elevated testosterone levels in PCOS rats and restored other blood biochemical parameters such as estrogen, progesterone and cholesterol levels and histology of ovarian tissue. The ovarian weights and uterine weights were also significantly recovered after the S. racemosa bark treatment. Aqueous extract of S. racemosa bark stimulated serum follicular stimulating hormone levels along with the rise in serum LH (luteinizing hormone) level as studied in in vivo effect in immature female Sprague-Dawley rats. Moreover, histopathological studies displayed enhanced folliculogenesis, presence of mature follicles and detached oocytes. The effect of S. racemosa was found to be comparable with clomiphene citrate (1 mg/kg) (Bhutani et al., 2004). 6.12. Antidiabetic activity Treatment of methanol extract of S. racemosa bark (250 and 500 mg/kg) in streptozotocin induced diabetic rats has resulted in reduced blood glucose and triglycerides levels after administration of extract. The possible mechanism behind this effect could be insulin like effect on peripheral tissues by either promoting glucose up-take metabolism or by inhibiting hepatic gluconeogenesis (Venkidesh et al., 2001). The altered serum lipid profile was reversed towards normal after treatment with the methanol extract. Methanol extract exhibited hypocholesterolemic and hypotriglyceridemic effects, while increased the levels of HDL in streptozotocin induced diabetic rats was observed comparable to the standard hypoglycemic drug glibenclamide (0.6 mg/kg). Thirumurugan et al. (2011) have evaluated the methanol extract of S. racemosa bark in an in vitro α-glucosidase enzyme inhibition assay. Voglibose was used as the positive control. The results showed 100% inhibition along with IC50 value of 8.16 µg/mL and reflected the potential of the extract to be an effective αglucosidase inhibitor; for further use in diabetes. 6.13. Activity against cardiovascular disorder Investigation on one Indian herbal formulation named Body Revival, having suspension of Symplocos racemosa Roxb., Aegle marmelos (L.) Correa (Rutaceae), Acorus calamus L. (Acoraceae), Rubia cordifolia L. (Rubiaceae), Saussurea lappa (Decne) Sch.Bip. (Asteraceae), Blumea lacera (Burm. f.) DC. (Asteraceae), Rumex vasicarius L. (Polygonaceae), Cucumis melo L. (Cucurbitaceae) and honey showed that the formula was found to potentiate the cardio protection against isoproterenol induced myocardial ischemia and Adenosine diphosphate (ADP) or collagen induced human platelet aggregation (Sur et al., 2011). 6.14. Lipoxygenase and urease inhibitory activity In mammalian cells, lipoxygenase constitutes a family of iron containing key enzymes in the biosynthesis of a variety of bioregulatory compounds such as hydroxyeicosatetraenoic acids, leukotriene, lipoxins and hepoxylines. It has been found that these lipoxygenase products play a role in a variety of disorders such as bronchial asthma, inflammation and tumour angiogenesis; whereas urease is directly involved in the formation of infection stones and contributes to the pathogenesis of urolithiasis, pyelonephritis, ammonia and hepatic encephalopathy, hepatic coma and urinary catheter encrustation. Abbasi et al. (2005) have evaluated the activity of ethyl substituted glycoside, 1-ethyl brachiose-3’-acetate along with ketochaulmoogric acid, nonaeicosanol, triacontyl palmitate and methyl triacontanoate isolated from n-butanol fraction of methanol extract of S. racemosa bark using in-vitro lipoxygenase and urease inhibition assay. The findings on this study displayed the inhibitory potential of 1-ethyl brachiose-3’-acetate and triacontyl palmitate against lipoxygenase and urease enzyme with triacontyl palmitate showing concentration dependent effects. Baicalein and thiourea were used as the positive control (Lodhi et al., 2007) in the reported study. 6.15. Central nervous system depressant activity The aqueous extract of S. racemosa bark has demonstrated the central nervous system depressant activity by reducing the spontaneous motor activity in treated animals (Badoni et al., 2010) 6.16. Butyrylcholinesterase inhibitory activity Ahmad et al. (2006) have evaluated butyrylcholinesterase inhibitory activity of symcososide isolated from bark of S. racemosa. 6.17. Snake venom inhibitory activity Phenolic glycosides, benzoyl salireposide, salireposide, symploracemoside and symplomoside (500-25 µM/mL) from S. racemosa were evaluated for their inhibitory activity against snake-venom phosphodiesterase-I. Symploracemoside showed moderate inhibitory activity with an IC50 value of 590 mM, while symplomoside showed a weak activity with an IC50 value of 998 mM, as compared to the strong inhibitory potential of benzoyl salireposide (IC 50 , 171 mM) and moderate inhibitory activity of salireposide (IC50, 544 mM). Benzoyl salireposide and salireposide were also evaluated for their inhibitory activity against human nucleotide pyrophosphatase phosphodiesterase-I. Benzoyl salireposide showed inhibitory activity with an IC50 value of 90 mM, whereas salireposide showed a weak activity with an IC50 value of 383 mM. Phenolic glycosides, symplocomoside, symponoside, symplososide, and symploveroside isolated from S. racemosa displayed in vitro inhibitory activity against phosphodiesterase-I with IC50 values of 122, 698, 722, and 909 mM, respectively (Ahmad et al., 2003; Choudhary et al., 2004; Gupta and Pehsin, 2012). 6.18. Hypolipidemic activity Naik et al. (2013) studies on hypolipidemic activity of ethanolic extract (200 and 400 mg/kg) of S. racemosa by triton-WR 1339 (acute) and high fat diet (chronic) induced hyperlipidemic rat model showed significant reduction in the elevated serum lipids, restored the decreased high density lipoprotein (HDL) and improved the atherogenic index. In high fat diet (chronic) induced hyperlipidemic rat model, extract has prevented the increased formation of malondialdehyde in liver, restored the depleted levels of glutathione, super oxide dismutase and catalase significantly. The results were found comparable with the standard drug simvastatin (10 mg/kg p.o.). The results revealed significant hypolipidemic activity of the preparation compared to gentamicin as a standard 6.19. Wound healing activity Jatyadi taila is a medicated oil preparation containing S. racemosa popularly used for topical wounds and characterized by the presence of essential oil, flavonoids, alkaloids, steroids, tannins and glycosides. It has been found to reduce the wound area significantly and in dose dependent manner with increased proteins, hydroxyproline, hexosamine content in the granulation tissue in excision wound model in rats comparable to the topical preparation Neosporin as a reference standard (Shailajan et al., 2011). Further researchers have also evaluated the burn wound healing potential of Jatyadi taila and Jatyadi ghrita using experimentally induced burn injury in rats. The result showed the potential effect as compared to 1% silver sulfadiazine cream (Dhande et al., 2012). 6.20. Immunomodulatory activity An indigenous herbal extract IM-133N (0-125 µg/mL) containing extracts of S. racemosa and Prosopis glandulosa Torr. (Fabaceae) has been evaluated for potential immunomodulatory effects using RAW264.7 and THP-1 cells. The results indicated that noncytotoxic doses of IM-133N effectively up-regulated iNOS, TNFα, IL-6, IL-10, IL8 and IFNγ gene expression in both the RAW264.7 and THP-1 cells. IM-133N elicited doserelated increases in nitric oxide and tumor necrosis factor (TNF)-α production by RAW264.7 and THP-1 cells. These results demonstrated that IM-133N could stimulate nitric oxide and induced pro-inflammatory cytokine expression by monocytes/macrophages. As clinical studies have shown IM-133N to be an effective immunomodulator without any adverse effects, the results of the study provide further support for the potential use of S. racemosa as an immunostimulant or as an immunotherapy adjuvant (Varma et al., 2015). 6.21. Activity against GI disorders Dasamularista has been evaluated for the preliminary pharmacological activities by gastrointestinal motility test with barium sulphate milk, castor oil induced antidiarrheal test, hypnotic action of phenobarbital and acetic acid induced abdominal writhing assay. The result showed that it slightly reduced the intestinal motility, antidiarrheal property of formulation in castor oil induced Diarrhea by reducing purging index value. It did not alter the acetic acid induced abdominal writhing. The result showed significant reduction on the onset of sleeping time and increased duration of sleep in phenobarbital induced sleeping test (Rajia et al., 2006). Table 4: Summary on pharmacological reports of S. racemosa Reported PA Part used Tested substance Antiarthritic activity Bark Phenolic Phosphodiesterase-I 500glycosides: enzyme inhibition 25µM/mL benzoyl assay salireposide and salireposide benzoyl Phosphodiesterase-I 500salireposide, enzyme inhibition 25µM/mL salireposide, assay symconoside A and B Snake venom Bark inhibitory activity Model Dose References Choudhary et al., 2004 Choudhary et al., 2004; Ahmad et al., 2005 Female disorders Stem (Folliculogenesis) bark Lipoxygenase and Bark urease inhibitory activity Anticancer Antioxidant Bark Aqueous extract In-vivo effect on FSH 500-1000and LH levels in 2000 mg/Kg immature female Sprague-Dawley rats Ethyl substituted In-vitro lipoxygenase 1 mM glycoside: 1-ethyl and urease inhibition assay brachiose-3’acetate, ketochaulmoogric acid, nonaeicosanol, triacontyl palmitate and methyl triacontanoate 0.005-100 Butanolic extract In-vitro XTT assay against HL60 (Human μg/mL leukemia cell line, HeLa (Human cervix cancer cell line) Abbasi et al., 2005 Raval et al., 2009 Ethanolic extract In-vitro MTT assay 6.125 -100 against MCF-7 (breast μg/mL cancer) cell line Ethanolic extract In-vivo antitumor 100 and Vijayabaska activity against 200mg ran, 2010(b) Ehrlich ascites carcinoma (EAC) in swiss albino mice Thymidine 0-5 mM Hussain et phosphorylase enzyme al., 2009 inhibition assay phenolic glycosides: symplocomoside and Symponoside Water, alcohol Brine shrimp bio- 1-5000 and hydro- assay μg/mL alcoholic extracts Leaves Ethanolic extract Lipid peroxidation, 100 and 300 and superoxide dismutase mg/kg floweri and catalase activity in ng tops swiss albino mice Bark Bhutani et al., 2004 Ethanolic extract ABTS scavenging assay DPPH scavenging assay nitric oxide scavenging assay hydroxyl radical 0-15 mM 20-100 μg/mL 5-100 μg/mL 5-100 Vijayabaska ran, 2010(a) Subbaraju et al., 2006 Devmurari, 2010 Vijayabaska ran et al., 2010(c) activity μg/mL --- Bark Ethanolic extract DPPH scavenging assay Naik et al., 2014 Antimicrobial activity Bark Petroleum ether and Ethanolic extract Agar well diffusion 100, 300, Devmurari, method against gram 500 and 700 2010 positive bacteria μg/well Staphylococcus aureus, Enterococcus faecalis, Bacillus cereus and gram negative bacteria pseudomonas aeruginosa and Escherichia coli Activity against skin disorders Bark Ethanolic extract In-vitro disc diffusion 100 mg/mL Kumar et and broth dilution al., 2007 method against Propionio bacterium acne and Staphylococcus epidermidis Antipyretic Bark Ethanolic extract Antidiarrheal Bark Antiulcer Bark Hepatoprotective activity Bark In-vivo brewer’s yeast 100 and 200 Vijayabaska induced elevated rectal mg/kg (i.p.) ran et al., temperature in rats 2010(e) Extract Potent activity on --Semwal et induced Diarrhea al., 2011 Aqueous and Pylorus ligation, 250 and 500 Saifuddin et ethanolic extract aspirin and ethanol mg/kg (p.o.) al., 2010 of mixture of S. induced ulcer model in racemosa bark rats and Asarum europaeum L. root Aqueous and Pylorus ligation and 250 and 500 Gopala ethanolic extract aspirin induced ulcer mg/kg (p.o.) Krishna et model in rats al., 2013 100 and 200 Vijayabaska Ethanolic extract In-vivo DMBA induced hepatocellular mg/kg(p.o.) ran et al., 2010 carcinoma in rats (significantly reduced the levels of hepatic enzymes and total bilirubin and increased the levels of total proteins, reduced Anthelmintic Bark Activity against cardiovascular disorder Bark Wound healing activity --- Antidiabetic Bark Antiandrogenic Bark Analgesic and Bark Antiinflammatory Hypolipidemic activity Bark glutathione, catalase and superoxide dismutase) 250 and 500 Somani et Ethanolic extract In-vivo carbon tetrachloride (CCl4) mg/kg (p.o.) al., 2011 induced hepatic damage in rats 250 and 500 Venkidesh Methanolic extract In-vivo carbon tetrachloride (CCl4) mg/kg (p.o.) et al., 2011 induced hepatic toxicity in rats Petroleum ether, Anthelmintic activity 2.5, 5, 10, Rao et al., chloroform and against adult Indian 25 and 50 2011 ethanolic extract earthworm Pheretima mg/mL postthuma Body Revival Isoproterenol induced 200 and 400 Sur et al., formulation myocardial ischemia mg/kg 2011 and adenosine diphosphate or collagen induced human platelet aggregation Jatyadi taila Granulation tissue in --Shailajan et excision wound model al., 2011 in rats Methanolic extract Streptozotocin 250 and 500 Venkidesh, induced diabetic rats mg/kg 2012 Methanolic extract in vitro α-glucosidase --Thirumurug enzyme inhibition an et al., assay 2011 Aqueous extract Letrozole induced 250, 500 Jadhav et polycystic ovary and 1000 al., 2013 syndrome (PCOS) rat mg/kg model Ethanolic and Formalin induced paw 200 mg/kg Sharma et aqueous extract licking, tail flick al., 2013 model and carrageenan-induced rat paw oedema model Ethanolic extract Triton-WR 1339 200 and 400 Naik et al., (acute) and high fat mg/kg 2013 diet (chronic) induced hyperlipidemic rat model Immunomodulator --y activity Indigenous herbal Using RAW264.7 and 0-125 extract THP-1 cells µg/mL IM-133N Varma et al., 2015 Activity against GI --disorders Dasamularista Rajia et al., 2006 α-chymotrypsin inhibitory effect Locoracemoside A,B,C Bark Gastrointestinal 10 mL/kg motility test with barium sulphate milk, castor oil induced antidiarrheal test, hypnotic action of phenobarbital and acetic acid induced abdominal writhing assay In-vitro α- --chymotrypsin assay Rashid et al., 2007 7. Standardization report on S. racemosa Nagore et al., (2014) have developed quantitative high-performance thin-layer chromatography (HPTLC) method for the determination of loturine in different bark extracts of S. racemosa. Analysis of loturine was performed on HPTLC aluminium plates pre-coated with silica gel 60 F254 as a stationary phase, chloroform: acetonitrile: triethylamine (7:5:2 v/v/v) as mobile phase followed by densitometric scanning at 280 nm using Camag TLC scanner-3. Loturine was appeared as bluish colored chromatographic zones on a florescent background at Rf value 0.60. Also a simple RP-HPLC (reverse phase 288 mm × 4.6 mm, 5μ, Zorbax SB C-18 column) method was developed for determination of loturine from extract and formulation with scanning wavelength 288 nm using photodiode array detector (PDA). Loturine was separated using mobile phase 50 mM of ammonium acetate in water at pH 8.7 with triethylamine (solvent A) and acetonitrile (solvent B) at flow rate 1 mL min-1. Also they have developed RP- HPLC method for the quantification of Gallic acid at wavelength 280 nm using Inertsil C8-4 (250 x 4.6) mm, 5µ column. The Gallic acid was satisfactorily resolved with retention time at 8.5 minutes. Shah and Shailajan, (2010) have developed a simple, sensitive and accurate HPTLC method for quantification of β- sitosterol from the stem bark of S. racemosa using precoated silica gel 60 F254 with toluene- methanol, as a mobile system followed by 10 % methanolic sulphuric acid reagent and detection and densitometric quantitation was done at 366 nm. The concentration of β- sitosterol was found to be 0.222 mg g-1 in the stem bark collected from Madhya Pradesh, 0.1281 mg g-1 from Kutch (Gujarat) and 0.1685 mg g-1 from Mahabaleshwar (Maharashtra), while the concentration of βsitosterol was 0.0780 mg g-1 in wama tablets (containing Lodhra (S. racemosa, Ashok (Saraca indica L. (Leguminosae)), Ulatkamal (Abroma augusta (L.) L.f. (Malvaceae)), Daruharidra (Berberis aristata DC. (Berberidaceae)), Devdaru (Cedrus deodara (Roxb) Loud. (Pinaceae)), Tagar (Valeriana wallichii DC. (Valerianaceae)), Chandraprabha powder, Hirabol (Commiphora myrrha (Nees.) Engl. (Burseraceae)) used for menopausal problems and 0.11 mg g-1 in lucorin formulation used against Leucorrhoea. Physicochemical analysis and HPTLC has been reported for Laghugangadhar churna. (Rathi et al., 2010) Ayurvedic formulation Nyagrodhadi churna has been standardized by modern scientific quality control method. The obtained chemical and physical parameters can be adopted to lay down for the new pharmacopoeial standards (Gopala Simha and Laxminarayan, 2007). 8. Toxicological aspects on S. racemosa According to Ayurvedic system of medicine, the clinical dose of S. racemosa for adult is 3-5g of powder and 20-30g of decoction per day (Ayurvedic Pharmacopoeia of India, 2001). The acute oral toxicity study of ethanol extract of S. racemosa bark (2000 mg/kg) according to OECD (The Organisation for Economic Co-operation and Development) guideline 423 in Swiss albino mice, showed that extract did not show any signs or symptoms of toxicity and mortality after for 14 days (Vijayabaskarn et al., 2010; Somani et al., 2011). One of the report by Hussain et al. (2009) have focused on the toxicity assay of symplocomoside and symponoside, glycosides isolated from the bark of S. racemosa. The result revealed that both the compounds were found to be non-cytotoxic. Gopala Krishna et al., 2013 have evaluated aqueous and ethanolic extract of S. racemosa bark for acute oral toxicity study according to OECD guideline 420 using Albino Wister mice and found safe up to 2000 mg/kg body weight. Further, Saifuddin et al. (2010) have also demonstrated safety of aqueous and ethanolic extract of mixture of S. racemosa bark and Asarum europaeum L. (Aristolochiaceae) root without any signs or symptoms of toxicity and mortality. 9. Patent information on S. racemosa Various herbal drug formulations containing S. racemosa have been patented and having wound healing activity, skin whitening property, immunostimulant property and also indicated in gynecological and uterine disorders. Herbal drug composition containing S. racemosa has been patented for the management of gynecological disorders by Dabur research foundation (Patent no: US 6455077 B2) and wound healing property has also been patented (Patent no: EP 2 112 929 B1, US 200900748 79 A1). Patent no: US 20050238736 A, US 7943181 B2 on the composition comprising of extract of S. racemosa and/or plant Prosopis glandulosa Torr. (Fabaceae) showed natural immunostimulant effects. A cosmetic skin lightening formula comprising an extract of plants from the genus of Symplocos or Rubia has been patented by Lever Hindustan Ltd. (Patent no: 20060228309, WO 2004105718 A1) supporting the mention of the traditional claim on this drug to be used for skin whitening. Herbal formulation containing S. racemosa and other agents, has been patented by Shiseido Co. Ltd. (Patent no: US 20040038859 A, US 20060159782 A1) as it was reported to exhibit skin basement membrane stabilizing, matrix metalloproteinase inhibitory and artificial skin formation effects. The herbal drug formulations containing S. racemosa manufactured and marketed by local companies situated at Maharashtra, Madhya Pradesh, Uttar Pradesh, Uttarakhand, Gujarat (India) which are used in various uterine disorders, gynecological disorders, GI disorders and skin disorders. Table 5 summarizes the marketed herbal formulations with the details of part of S. racemosa used with dose and indications along with brand name and company name. Table 5: Marketed herbal formulations containing S. racemosa Name Company name Part Dose Indications 5mL thrice a day Menorrhagia, Irregular used M2-tone Charak Pharma, Bark syrup Mumbai, India and menstruation, Dysmenorrhea, leaves Leucorrhoea, Gynecological disorder M2-tone Charak Pharma, Bark Tablets Mumbai, India and 2 tablets twice a Menorrhagia, Irregular day leaves menstruation, Dysmenorrhea, Leucorrhoea, Gynecological disorder M2-tone Charak Pharma, Bark Forte syrup Mumbai, India 5mL twice a day Polycystic ovarian disorder and leaves Evecare Himalaya Herbal Bark syrup As directed by Premenstrual syndrome, physician Menorrhagia, Irregular menstruation, Dysmenorrhea, Leucorrhoea, Uterine disorder Evecare Himalaya capsule India Styplon Himalaya tablets India Herbal, Bark 2 capsules twice Uterine disorder, a day Herbal, Bark Gynecological disorder As directed by Bleeding gum, Hemorrhoids, physician Epistaxis, Hematuria Himfertin Himalaya veterinary India Herbal, Bark capsules Anoestrus, sub/silent oestrus, Uterine disorder daily for 2 days 2-3 capsules Lueco rest Pranacharya bhavan, Bark As directed by Leucorrhoea Tablets physician U.P., India Lueco rest Pranacharya bhavan, Bark As directed by Leucorrhoea syrup U.P.,India physician Lukol Himalaya syrup India Herbal, Bark As directed by Leucorrhoea associated with physician pelvic inflammatory, bacterial vaginitis Mucuskure Tansukh syrup U.P.,India Herbal, Bark extract 1-2 teaspoon 2-3 Colitis, Amoebiasis, Diarrhea, times a day Ulcerative colitis, Antiinflammatory, Antispasmodic Mucuskure Tansukh Capsule U.P.,India Herbal, Bark 2 capsules 2-3 Colitis, Amoebiasis, Diarrhea, times a day Ulcerative colitis, Antiinflammatory, Antispasmodic Eve syrup pro Ayusearch drugs & Bark laboratory Haryana, extract India 2-3 teaspoonful Menorrhagia, Irregular 3 times a day menstruation, Dysmenorrhea, Leucorrhoea, Uterine disorder, Gynecological disorder, Tension, Anxiety, Calcium & iron deficiency Lukosar Ayusearch drugs & Bark capsules laboratory Haryana, extract India Lukosar Ayusearch drugs & Bark tablets laboratory, Haryana, extract India Adult: 1-2 Leucorrhoea teaspoonful 3 to 4 times a day Child: ½-1 teaspoonful 3 to 4 times a day 1-2 tablets thrice Leucorrhoea a day Femisar Ayusearch drugs & Bark syrup laboratory, Haryana, extract 2-3 teaspoonful Menorrhagia, Irregular 3 times a day menstruation, Dysmenorrhea, India Leucorrhoea, Uterine disorder, Gynecological disorder Deogrip Sethi Rasayan shala, Satva 3-4 drops Antiaging agent, lotion drop M.P.,India (External) Rejuvenating agent, Tighten the vagina for women Femi cure Sure syrup Bark 10-20 mL twice Anemia, Menstrual disorder, a day cure remedies, M.P., Leucorrhoea India Rup nikhar Sethi Rasayan shala, Bark 1 teaspoon (with Antiaging agent, Skin lep milk M.P.,India or rose whitening property water & 1 drop glycerin) Ampucare Venus remedies, Bark lotion Chandigarh External use (U.T.), Wound healing agent, Antimicrobial India Diaron Mahesheari Bark 2-4 teaspoonful Antidiarrheal, Antidysenteric, syrup/Tab Pharmaceuticals, twice a day/ 2-4 Antispasmodic, U.T., India tablets twice a Antidysenteric day Arogita Alna vedic, Tvak Uterine Chandigarh syrup India Colovin Solankiz capsules Care, Gujarat, India 2 teaspoonful Uterine tonic (U.T.), (skin/b thrice a day ark) Health Bark 2 capsules daily Colitis, Amoebiasis, Diarrhea, Ulcerative colitis, Antiinflammatory, Antispasmodic Gynova tablets Millennium Herbal, Mumbai, India Bark 2 tablets twice a day after meal Dysmenorrhea, Oligomenorrhoea, Infertility, Premenstrual syndrome Gynova syrup Millennium Herbal, Mumbai, India Bark 10-15 mL twice a day after meal Dysmenorrhea, Oligomenorrhoea, Infertility, Premenstrual syndrome Fairness cream Vasu Herbal, Gujarat, India Bark External use Cleaning and soothing agent 10. Clinical studies on S. racemosa Many clinical study reports are available on the polyherbal formulations containing S. racemosa for the treatment of skin disorders, menstrual irregularities, acne, bedsores and vitiligo. Exher is a uterine tonic formulation containing S. racemosa was evaluated for its oestrogenic (250 and 500 mg/kg p.o.) effects using in-vivo and in-vitro experimental model for a period of 21 days. The result showed that it possesses oestrogenic activity only in the presence of functional ovary. It also displayed preventive effects on uterine fibroids, abnormal uterine bleeding and can be used in menstrual irregularities as it was found safe on rat oestrus cycle by maintaining the regular oestrus cycle (Hanumantharayappa et al., 2014). Siriwardena et al. (2009) have assessed the efficacy of S. racemosa on asrugdara with specific reference to menorrhagia in a clinical study on 52 females aged between 16-45 years suffering from excessive and or irregular vaginal bleeding. The treatment of 5 g drug powder twice a day orally for the duration of one month has resulted in significant reduction in cardinal symptoms at the end of the study and was found to be effective in menorrhagia. Umarji and Patki, (2012) have also described efficacy and safety of Evecare Syrup, a formula with S. racemosa in menstrual irregularities in one clinical study on 1,000 female patients aged between 18-45 years. Singh et al. (2013) have evaluated efficacy and safety of Ampucare lotion containing S. racemosa; in patients with bedsores. They have selected one hundred patients of either sex having more than 18 years of age and advised to apply lotion locally once a day. The result showed that it markedly accelerates wound healing in patients with bedsore after the treatment. Soni et al. (2011) have explained safety and efficacy of poly herbal fairness cream containing S. racemosa on fifty subjects. The findings showed significant reduction in dark complexions, increase in skin softness and skin glowing effect at the end of the study with no adverse effects reported with twice a day application for 30 days. Lodhra and Nyagrodha have been evaluated in 40 diagnosed patients of shveta-pradar between age group 18-45 years. The finding showed that the treatment of vaginal wash with decoction of lodhra bark exhibited better effect than the treatment of lodhra twak churna with Nyagrodha twak kasaya (Sharma et al., 2015). One more formulation, Tutthadi lepa has also been evaluated in the psoriasis patients. 20 patients have been selected for the study and have been given Tutthadi lepa with mustard oil at bed time for the local application for a period of 4 months. The result revealed that 75% patients have been relieved and 25% patients have been improved whereas no side effects have been observed in psoriasis patients except mild irritation (Agarwal et al., 2008; Singh et al., 2014.). Keratoconus is a common corneal disease that leads to progressive dimness of vision due to central corneal thinning. Jeevantyadi ghrita containing S. racemosa has been evaluated in the management of Keratoconus. Thirty patients have been selected with total 53 eyes affected among them. The findings showed the effectiveness of the formula in the improving corneal thickness and overall associated symptoms of Keratoconus (Manju sree and Ashwini, 2013). Acne vulgaris is a distressing condition considered as an adolescent disorder related to pilosebaceous follicle. One formula “Sarivadyasava” has been evaluated in the 20 patients with acne vulgaris, where the patients were given 25mL of Sarivadyasava orally thrice in a day for 28 days. The results revealed significant response in reducing signs and symptoms of Acne vulgaris (Rathod and Kamat, 2012). Candanasava has been evaluated in the treatment of urinary tract infection in 40 patients in the age group between 21-30 years. Study showed significant symptomatic improvement with marked changes in urinary alterations with the use of Candanasava (Goel and Singh, 1991). Rakta pradara or abnormal uterine bleeding, regular or irregular with alterations in amount or duration of menstrual loss, commonly implies to excessive regular menstrual bleeding or essential menorrhagia. Ayurvedic formulation lodhrasava has been evaluated in the patients of rakta pradar. Total 46 cases age ranging between 15-45 years, and duration of illness 6-24 months were included in the study after thorough examination. Lodhrasava has been given 30 mL thrice in a day. The efficacy of Lodhrasava was found to be highly significant may be due to presence of loturine alkaloid and α-spinosteral (Prameela Devi, 2007). 11. Conclusion This scientific and systematic study on S. racemosa focuses on the ethnobotanical and traditional uses, phytochemistry, pharmacologic potential, toxicity studies of different extracts, Ayurvedic and herbal formulations to provide the link between ongoing research and ethnobotanical claims. Ethno botanical literature indicates that S. racemosa is used in treatment of uterine disorders, eye, ear and skin diseases, liver and bowel complaints, tumors, asthma, fever, snake-bite, gonorrhea and arthritis. The systematic and scientific research has been desirable to prove and validate the unexplored ethnobotanical claims and traditional utility of different plant parts. Furthermore, phytochemistry of bioactives has been reported and studied well for various in vitro and in vivo therapeutic claims. Varieties of Ayurvedic and herbal formulations are available in the market for treating different ailments, but only few are standardized and evaluated systematically, however some formulations have been patented by various researchers. Moreover, non-medicinal uses on S. racemosa have also been reviewed systematically in this report. Recent reports on S. racemosa have focused on anticancer, antibacterial, analgesic & antiinflammatory, antipyretic, antioxidant, hepatoprotective, antiandrogenic and antiulcer activity ascribed to the presence of phenolic glycosides, flavonoids, steroids and triterpenoids. However scientific evidences on its effectiveness against gonorrhea, bowl complaints and varied type of cancer are still lacking. The comprehensive information as presented in this review on phytochemistry and pharmacological activities of the plant strongly recommends a huge biological potential of the bark thorough indication of its potential in different diseases. It has been found that studies on bark of S. racemosa have been extensively focused by various research groups for activity guided isolation of bioactives but the aerial parts remained unexplored for pharmacological assessment in spite of phytochemical review suggesting presence of more than fifteen different types of flavonoid glycosides in ethyl acetate soluble fraction of methanol extract. These facts clearly demonstrate the need for further exploration of aerial parts for pharmacological activities. S. racemosa bark is a rich source of different types of phenolic glycosides and many of them have been studied extensively for specific effects for e.g. benzoyl salireposide and salireposide were reported with phosphodiesterase inhibitory activity, ethyl substituted glycoside: 1-ethyl brachiose-3’-acetate, ketochaulmoogric acid, nonaeicosanol, triacontyl palmitate and methyl triacontanoate displayed lipoxygenase and urease inhibitory activity and phenolic glycosides like symplocomoside and symponoside have been reported with thymidine phosphorylase inhibitory activity. Phenolic glycosides like symplocomoside, symponoside, symplososide, and symploveroside have been reported for their in vitro snake venom inhibitory effects. These reports indicate potential of different bioactives from bark in various ailments. Apart from this bark has been found to contain triterprnoids such as ursolic acid, oleonolic acid, betulinic acid, β-amyrin and steroids such as stigmasterol and βsitosterol. These phytoconstituents have been responsible for the anticancer, antiviral, antibacterial, antimalarial, antiinflammatory, anticholesteremic activities. There are very few in vitro studies showing protective effects using various cell line model of cancer have been reported nonetheless detail preclinical assessment of extract as well as bioactives is mandatory to establish anticancer effects of bark. The research has been needed to prove and validate the efficacy of bio-markers through the well -designed clinical studies. It has been used as a drug of choice in the treatment of gynecological conditions like menorrhagia, leucorrhoea and other menstrual complaints. It is also useful in abortions, miscarriages and vaginal ulcers. Various Ayurvedic and herbal formulations containing bark of S. racemosa are available in market for treating different ailments and some formulations have been patented also by various researchers, but only few have addressed the systematic evaluation of bioactives with special reference to individual drug. The systematized studies can be planned for the unexplored bio-markers to establish their efficacy and to validate the traditional claim of this drug in clinical practice after proper safety assessment. However, efforts are required in developing the clinical studies on bio-markers with evaluation of pharmacokinetic and pharmacodynamic parameters to fulfill the Western standards of evidence-based medicine. The profound review on literature mirrors the potentiality and thrust areas for related studies of bark and its active constituents like phenolic glycosides. S. racemosa is vulnerable but facing the high risk of extinction in the wild due to limited geographical distribution. However, S. racemosa has been regenerated by the researchers at the location Talacauvery in Karnataka using seed propagation and vegetative propagation method for the development of the seedlings. But it was observed that the fruits of this plant have severely infested with larvae of beetles and emergence was observed after one day of collection, seeds could retain viability for 3 months only. So, to overcome these problems advanced bio technological practices should be developed. It also demands maintenance of the natural flora with the advent of tissue culture techniques for the preservation of the specie and to increase the trade (commercialization) as S. racemosa is meeting the high risk line of extinction in the wild due to limited geographical distribution. 12. 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