Rev. Inst. Med. Trop. Sao Paulo 54(5):273-280, September-October, 2012 doi: 10.1590/S0036-46652012000500007

PHARMACOLOGICAL EFFECTS OF mukorossi

Aparna UPADHYAY & D.K. SINGH

SUMMARY

Sapindus mukorossi is an extremely valuable medicinal , distributed in tropical and sub-tropical regions of Asia. The aim of present review is to form a short compilation of the phytochemical composition and pharmacological properties of this multipurpose . The main phytoconstituents isolated and identified from different parts of this plant are triterpenoidal of , and tirucullane type. The structure and chemical names of all the types of triterpenoidal saponins reported in are included in this review. Many research studies have been conducted to prove the plant’s potential as being spermicidal, contraceptive, hepatoprotective, emetic, anti-inflammatory and anti-protozoal. The present review highlights some of the salient pharmacological uses of Sapindus mukorossi.

KEYWORDS: Sapindus mukorossi; Pharmacology; Saponins.

INTRODUCTION pericarp” and in China “wu-huan-zi”, the “non-illness ”37. The major compounds isolated from Sapindus mukorossi are triterpenoidal saponins Sapindus mukorossi Gaertn., a member of the family , is of mainly three oleanane, dammarane and tirucullane types. Recently commonly known by several names such as soapnut, soapberry, washnut, many of the pharmacological actions of this plant have been explored reetha, aritha, dodan and doadni. It is a tree widely grown in which includes the antimicrobial19, cytotoxic29, molluscicidal16,42, upper reaches of Indo-Gangetic plains, Shivaliks and sub Himalayan insecticidal12,26, piscicidal44 and fungicidal37,41 activities. One of the most tracts at altitudes from 200 m to 1500 m. The Sapindus mukorossi is a talked about activities of this plant is the contraceptive activity of the fairly large, deciduous tree with a straight trunk up to 12 meters in height, saponins extracted from the pericarp of the fruit11,27. sometimes attaining a height of 20 m and a girth of 1.8 m, with a globose crown and rather fine leathery foliage. Bark is dark to pale yellow, fairly Sapindus mukorossi is well known for its folk medicinal values30. smooth, with many vertical lines of lenticels and fine fissures exfoliating Pericarps of Sapindus mukorossi have been traditionally used as an in irregular wood scales. The blaze is 0.8-1.3 cm, hard, not fibrous, pale expectorant as well as a source of natural surfactant20. Due to the presence orange brown, brittle and granular. are 30-50 cm long, alternate, of saponins, soapnut is well known for its detergent and insecticidal paripinnate; common petiole very narrowly bordered, glabrous; leaflets properties and it is traditionally used for removing lice from the scalp. 5-10 pairs, opposite or alternate, 5-18 by 2.5-5 cm, lanceolate, acuminate, The are of considerable importance for their medicinal value for entire, glabrous, often slightly falcate or oblique; petioles 2-5 m long. treating a number of diseases like excessive salivation, pimples, epilepsy, Inflorescence is a compound terminal panicle, 30 cm or more in length, chlorosis, migranes, eczema and psoriasis21. The powdered are with pubescent branches. are about 5 mm across, small, terminal, employed in the treatment of dental caries, arthritis, common colds, polygamous, greenish white, subsessile, numerous, mostly bisexual. constipation and nausea8. The seeds of Sapindus mukorossi are used in Sepals 5, each with a woolly scale on either side above the claw. Fruits are Ayurvedic medicine to remove tan and freckles from the skin. It cleanses globose, fleshy, 1-seeded drupe, sometimes two drupels together, about the skin of oily secretion and is even used as a cleanser for washing hair 1.8-2.5 cm across. Seeds are 0.8-1.3 cm in diameter, globose, smooth, as it forms a rich, natural lather. The leaves are used in baths to relieve black and loosely placed in dry fruit7. joint pain and the roots are used in the treatment of gout and rheumatism. Since ancient times Sapindus mukorossi has been used as a detergent for The fruit is valued for the saponins (10.1%) present in the pericarp shawls and silks. The fruit of Sapindus mukorossi was utilized by Indian and constitutes up to 56.5% of the drupe known for inhibiting tumor cell jewelers for restoring the brightness of tarnished ornaments made of gold, growth37. In China and Japan it has been used as a remedy for centuries. silver and other precious metals33. In Japan its pericarp is called “enmei-hi”, which means “life prolonging

Malacology Laboratory, Department of Zoology, DDU Gorakhpur University, Gorakhpur, 273009, U.P. . Correspondence to: Prof. D.K. Singh, Malacology Laboratory, Department of Zoology, DDU Gorakhpur University, Gorakhpur, 273009, UP, India. Tel: +91 551 2202187(O)/0509(R). E-mail: [email protected] UPADHYAY, A. & SINGH, D.K. - Pharmacological effects of Sapindus mukorossi. Rev. Inst. Med. Trop. Sao Paulo, 54(5): 273-80, 2012.

PHYTOCHEMICAL CONSTITUENTS et al.24 reported the presence of Sapimukosides E-J24. The structures of Sapimukosides A-J are shown in Fig. 1 to Fig. 10 respectively. Table 1 The major constituents of Sapindus mukorossi fruit are saponins shows whole view of all the saponins isolated from Sapindus mukorossi. (10%-11.5%), sugars (10%) and mucilage10. Saponins are secondary plant metabolites with divergent biological activities10. Sapindus saponins are a mixture of six sapindosides (sapindosides A, B, C, D and mukorozi saponins (E1 and Y1), with sapindoside B as one of the major constituents, isolated by n-butanol extraction of the ethanolic extract of fruit pericarp of Sapindus mukorossi and identified by liquid chromatography and mass spectroscopy28. Saponins are a large family of structurally-related compounds of or triterpenoid aglycone () linked to one or more oligosaccharide moieties by glycosidic linkage. The aglycone, or sapogenin, may contain one or more unsaturated C-C bonds. The oligosaccharide chain is normally attached at the C3 position (monodesmosidic), but many saponins have an additional sugar moiety Fig R R at the C or C position (bidesmosidic)10. The great complexity of the 1 2 2,6 2,8 3-Ara H structure arises from the variability of the aglycone structure, the 1 Glc nature of the side chains and the position of attachment of these moieties 2-Rha on the aglycone10. The carbohydrate moiety consists of pentoses, hexoses or uronic acids. Due to this complexity, saponins are difficult to classify. 2 Glc6-Rha H Because it is no longer customary to classify compounds based on their 3-Ara physicochemical or biological properties, a state of the art classification 3 Glc Et based on the biosynthesis of the saponin carbon skeletons was proposed 2-Rha by VINCKEN et al.43. 3-Ara 4 Glc Me Different types of , saponins of oleanane, dammarane and 2-Rha tirucullane type were isolated from the galls, fruits and roots of Sapindus 3-Ara mukorossi. Oleanane type triterpenoid saponins named Sapindoside A&B 5 Glc Et 6 (Fig. 34 & 35) were reported from the fruits of Sapindus mukorossi . 2-Rha3-Ara Sapindoside C (Fig. 36)4, Sapindoside D (Fig. 37)5, which is a hexaoside 3-Ara of , and Sapindoside E (Fig. 38)3, a nonaoside of hederagenin, 6 Glc Et was isolated and identified from the methanolic extract of the fruits of 2-Rha3-Xyl Sapindus mukorossi. 3-Ara 7 Glc Me

Dammarane-type saponins, named Sapinmusaponins A & B (Fig. 11 2-Rha3-Xyl & 12), C-E (Fig. 15, 16, 17), together with three known phenylpropanoid 8 3-Ara Et , were isolated from the galls of Sapindus mukorossi45. Glc Tirucallane-type saponins, sapinmusaponins F-J (Fig. 18-22), were 2-Rha3-Ara isolated from the galls of Sapindus mukorossi as reported by HUANG 9 3-Rha Me 17 et al. . The structures of these saponins were elucidated on the basis of Glc spectroscopic analysis including 1D and 2D NMR techniques. 2-Rha3-Ara 10 Glc -Rha Et Triterpene saponins of oleanane type like, Sapinmusaponin K-N (Fig. 6 25-28), Mukorozisaponin G & E1 (Fig. 29-30), Sapindoside A & B along Abbreviations with dammarane types like Sapinmusaponin O and P (Fig. 13 & 14) were Glc:β-D-Glucopyranosyl isolated from fruits and the galls of Sapindus mukorossi as per HUANG Rha:α-L-hamnopyranosyl et al.15. In another study by NAKAYAMA et al.23, Mukorozisaponin Y1 Ara:α-L-rabinopyranosyl (Fig. 31), Y2 (Fig. 32), X (Fig. 33) were isolated from the pericarp of Xyl:β-D-Xylopyranosyl Sapindus mukorossi.

Fractionation of an ethanolic extract of the galls of Sapindus mukorossi BIOLOGICAL EFFECTS has resulted in the isolation of two tirucallane type triterpenoid saponins, sapinmusaponin Q and R (Fig. 23-24), along with three known oleanane 1. Anti-bacterial activity: IBRAHIM et al.19 evaluated that type triterpenoid saponins: sapindoside A, sapindoside B, and hederagenin- ethanolic and chloroform extracts of Sapindus mukorossi inhibited 3-O-[β-D-xylopyranosyl-(1→3)]-α-L-rhamnopyranosyl-(1→2)+-α-L the growth of Helicobacter pylori (both sensitive and resistant), at arabinopyranoside14. The roots of Sapindus mukorossi contain tirucallane- very low concentrations, when given orally for seven days to male type triterpenoid saponins like Sapimukoside A & B38, Sapimukoside C wister rats. In the in vitro study, the isolates show a considerable zone &D25. Further investigation of the roots of Sapindus mukorossi by NI of inhibition at very low concentration (10 µg/mL) and in the in vivo

274 UPADHYAY, A. & SINGH, D.K. - Pharmacological effects of Sapindus mukorossi. Rev. Inst. Med. Trop. Sao Paulo, 54(5): 273-80, 2012.

Table 1 List of Saponins isolated from Sapindus mukorossi

Saponins Chemical name Tirucullane/oleanane/ Structure Reference dammarane type Sapindoside A Hederagenin-3-O-α-L-arabinosyl-(2→1)-α-L- Oleanane 34 Chirva et al., 1970 a rhamnopyranoside B Hederagenin-3-O-α-L-arabinosyl-(2→1)-O-α-L- Oleanane 35 Chirva et al., 1970 a rhamnopyranosyl-(3→1)-β-D-xylanopyranoside C Hederagenin-3-O-β-D-glucosyl(1→4)-β-D-xylosyl Oleanane 36 Chirva et al., 1970 b (1→3)-α-L-rhamnosyl(1→2)- α-L-arabinoside Sapinmusaponin A 3,7,20(S),22-tetrahydroxydammar-24-ene-3-O-a-L- Dammarane 11 Yao et al., 2005 rhamnopyranosyl-(1→2)-D-glucopyranoside B 3,7,20(S),22,23-pentahydroxydammar-24-ene-3-O-a-L- Dammarane 12 Yao et al., 2005 rhamnopyranosyl-(1→2)-D-glucopyranoside C 3,7,20(S),22,25-pentahydroxydammar-23-ene-3-O-a-L- Dammarane 15 Yao et al., 2005 rhamnopyranosyl-(1→2)-D-glucopyranoside D 25-methoxy-3,7,20(S),22-tetrahydroxydammar-23-ene-3-O-a- Dammarane 16 Yao et al., 2005 L-rhamnopyranosyl-(1→2)-D-glucopyranoside, E 25-methoxy-3,7,20(R)-trihydroxydammar-23-ene-3-O-a-L- Dammarane 17 Yao et al., 2005 rhamnopyranosyl-(1→2)-D-glucopyranoside F 21 β-methoxy-3-β-21(S), 23I-epoxy tirucall-7,24-diene-3-O- Tirucullane 18 Huang et al., 2006 α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranosyl G 21α-methoxy-3-β-21(S), 23I-epoxy tirucall-7,24-diene-3-O-α- Tirucullane 19 Huang et al., 2006 L-rhamnopyranosyl-(1→6)-β-D-glucopyranosyl H 21α-methoxy-3-β-21(S), 23I-epoxy tirucall-7,24-diene-3-O- Tirucullane 20 Huang et al., 2006 α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranosyl I 21β-methoxy-3-β-21(S), 23I-epoxy tirucall-7,24-diene-3-O- Tirucullane 21 Huang et al., 2006 α-L-dirhamnopyranosyl-(1→2,6)-β-D-glucopyranosyl J 21α-methoxy-3-β-21(S), 23I-epoxy tirucall-7,24-diene-3-O- Tirucullane 22 Huang et al., 2006 α-L-dirhamnopyranosyl-(1→2,6)-β-D-glucopyranosyl K hederagenin-3-O-(3-O-acetyl-alpha-L-arabinopyranosyl)- Oleanane 25 Huang et al., 2008 (1→3)-alpha-L-rhamnopyranosyl-(1→2)-alpha-L- arabinopyranoside L hederagenin-3-O-(4-O-acetyl-alpha-L-arabinopyranosyl)- Oleanane 26 Huang et al., 2008 (1→3)-alpha-L-rhamnopyranosyl-(1→2)-alpha-L-arabino- pyranoside, M hederagenin-3-O-(2,3-O-diacetyl-beta-D-xylopyranosyl)- Oleanane 27 Huang et al., 2008 (1→3)-alpha-L-rhamnopyranosyl-(1→2)-alpha-L- arabinopyranoside N hederagenin-3-O-(2,4-O-diacetyl-beta-D-xylopyranosyl)- Oleanane 28 Huang et al., 2008 (1→3)-alpha-L-rhamnopyranosyl-(1→2)-alpha-L- arabinopyranoside O 3,7,20(S)-trihydroxydammar-24-ene-3-O-alpha-L- Dammarane 13 Huang et al., 2008 rhamnopyranosyl-(1→2)-beta-D-glucopyranoside P 3,7,20(R)-trihydroxydammar-24-ene-3-O-alpha-L- Dammarane 14 Huang et al., 2007 rhamnopyranosyl-(1→2)-beta-d-glucopyranoside Q 21α-methoxy-3β, 21I, 23(S)-epoxytirucall-7,24-diene-3-O-β- Tirucullane 23 Huang et al., 2007 D-glucopyranosyl-(1→2)-β-D-glucopyranoside R 21α-methoxy-3β, 21I, 23(S)-epoxytirucall-7,24-diene-3-O-α- Tirucullane 24 Huang et al., 2007 L-rhamnopyranosyl-(1→6)-β-D-glucopyranosyl-(1→2)-β-D- glucopyranoside

275 UPADHYAY, A. & SINGH, D.K. - Pharmacological effects of Sapindus mukorossi. Rev. Inst. Med. Trop. Sao Paulo, 54(5): 273-80, 2012.

Table 1 List of Saponins isolated from Sapindus mukorossi (cont.)

Sapinmukoside A 3-O-α-L-rhamnopyranosyl-(1→2)-*α-L- Tirucullane 1 Teng et al., 2003 arabinopyranosyl-(1→3)+ – β-D-glucopyranosyl-21, 23R-epoxyl tirucall-7, 24R-diene-3 β, 2-diol B 3-O-α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranosyl-21, Tirucullane 2 Teng et al., 2003 23R-epoxyl tirucall-7, 24R-diene-3 β, 21-diol C 3-O-α-L-rhamnopyranosyl-(1→2)-[α-L-arabinopyranosyl- Tirucullane 3 Teng et al., 2004 (1→3)]-β-D-glucopyranosyl (21,23R)-epoxyl tirucalla-7,24- diene-(21S)-ethoxyl-3β-ol D 3-O-α-L-rhamnopyranosyl-(1→2)-[α-L-arabinopyranosyl- Tirucullane 4 Teng et al., 2004 (1→3)]-β-D-glucopyranosyl (21,23R)-epoxyl tirucall-7, 24-diene-(21S)-methoxyl-3β-ol . E 3-O-α-L-arabinopyranosyl-(1→3)-α-L-rhamnopyranosyl- Tirucullane 5 Ni et al., 2006 (1→2)-[α-L-arabinopyranosyl-(1→3)]-β-D-glucopyranosyl (21,23R)-epoxyl tirucalla-7,24-diene-21β-ethoxyl-3β-ol} F {3-O-β-D-xylanopyranosyl-(1→3)-α-L-rhamnopyranosyl- Tirucullane 6 Ni et al., 2006 (1→2)-[β-L-arabinopyranosyl-(1→3)]-β-D-glucopyranosyl 21,23R-epoxyl tirucalla-7,24-diene-21β-ethoxyl-3β-ol} G {3-O-β-D-xylanopyranosyl-(1→3)-α-L-rhamnopyranosyl- Tirucullane 7 Ni et al., 2006 (1→2)-[α-L-arabinopyranosyl-(1→3)]-β-D-glucopyranosyl (21,23R)-epoxyl tirucalla-7,24-diene-21β-methoxy-3β-ol} H {3-O-α-L-arabinopyranosyl-(1→3)-α-L-rhamnopyranosyl- Tirucullane 8 Ni et al., 2006 (1→2)-[α-L-rhamnopyranosyl-(1→3)]-β-D-glucopyranosyl 21,23R-epoxyl tirucalla-7,24-diene-21β-ethoxy-3β-ol} I {3-O-α-L-arabinopyranosyl-(1→3)-α-L-rhamnopyranosyl- Tirucullane 9 Ni et al., 2006 (1→2)-[α-L-rhamnopyranosyl-(1→3)]-β-D-glucopyranosyl 21,23R-epoxyl tirucalla-7,24-diene-21β-methoxy-3β-ol} J {3-O-α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranosyl Tirucullane 10 Ni et al., 2006 21,23R-epoxyl tirucalla-7,24-diene-21β-ethoxyl-3β-ol} Mukorozi-saponin G Hederagenin-3-O-(2-O-acetyl-β-D-xylanopyranosyl)-(1→3)- Oleanane 29 Huang et al., 2008 α-L-rhamnopyranosyl-(1→2)-α-L-arabinoside. E1 Hederagenin-3-O-α-L-arabinosyl-(1→3)-α-L- Oleanane 30 Huang et al., 2008 rhamnopyranosyl-(1→2)-α-L-arabinoside. study the Helicobacter pylori infection was cleared with minimal dose 3. Spermicidal activity: Saponins from Sapindus mukorossi are extracts of 2.5 mg/mL. known to be spermicidal11,27. Morphological changes in human ejaculated spermatozoa after exposure to this saponin were evaluated under scanning 2. Insecticidal activity: Saponins possess insecticidal activity, electron microscopy. The minimum effective concentration (0.05% in spot causing mortality and/or growth inhibition in the insects tested, the test) did not affect the surface topography after exposure for one minute. cotton leafworm Spodoptera littoralis caterpillars and the pea aphid However, incubation of spermatozoa for 10 minutes resulted in extensive Acyrthosiphon pisum. In the experiments with Acyrthosiphon pisum, vesiculation and a disruption of the plasma membrane in the head region. 0.1% saponin killed all aphids, whereas with Spodoptera some Higher concentrations (0.1%, 1.25%, 2.5% and 5.0%) caused more or less caterpillars were still able to develop into apparently normal adults on similar changes which included vesiculation, vacuolation, disruption or food containing 7% saponin12. Saponins can be employed as novel natural erosion of membranes in the head region. These findings suggest that the tactics in integrated pest management (IPM) to control pest insects, which morphological changes observed are due to alterations in the glycoproteins fit in modern agriculture and horticulture13. Ethanolic extract of Sapindus associated with the lipid bilayer of the plasma membrane of spermatozoa8. mukorossi was investigated for repellency and insecticidal activity against This spermicidal property has been used in contraceptive cream9. Sitophilus oryzae and Pediculus humanus. Average mortality percentage indicated that the extracts caused significant mortality and repellency on 4. Anti-Trichomonas activity: TIWARI et al.39 demonstrated the target insects and bioassays indicated that toxic and repellent effect that the Sapindus saponin mixture shows anti-Trichomonas activity was proportional to the concentration26. at a 10-fold lower concentration (0.005%) than its minimal effective

276 UPADHYAY, A. & SINGH, D.K. - Pharmacological effects of Sapindus mukorossi. Rev. Inst. Med. Trop. Sao Paulo, 54(5): 273-80, 2012.

Fig R1 R2

18 Glc6-Rha β-OCH3 19 Glc -Rha -OCH Fig R1 R2 R3 R4 R5 6 α 3 20 Glc -Rha -OCH 11 Glc2-Rha H OH OH H 2 α 3 2-Rha 12 Glc2-Rha H OH OH OH 21 Glc -OCH 13 Glc2-Rha OH CH3 H H β 3 6-Rha 14 Glc2-Rha CH3 OH H H 2-Rha

22 Glc α-OCH3 6-Rha

23 Glc2-Glc α-OCH3 2-Glc

24 Glc α-OCH3

6-Rha

Dioscin, one of the steroidal saponins, and its aglycone also has an extensive anti-tumor effect by cell cycle arrest and apoptosis22. The preliminary bioassay data revealed that saponins [39,4]-43] showed

moderate cytotoxic activity (ED50~9-18µg/mL) against human tumor cell 29 Fig R1 R2 R3 lines (Hepa59T/VGH, NCL, HeLa and Med) . Strychnopentamine was the reference compound used in the study. All saponins were reported to 15 Glc2-Rha OH OH be at least five times less active than the reference compound36. 16 Glc2-Rha OH OCH3 17 Glc -Rha H OCH 2 3 6. Hepatoprotective activity: IBRAHIM et al.18 reported that the extracts of Sapindus mukorossi (2.5 mg/L) and Rheum emodi (3.0 mg/L) spermicidal concentration against human spermatozoa (0.05%)11. have a protective capacity both in vitro on primary hepatocytes cultures

Saponin concentration dependently inhibited the ability of parasites and in vivo in a rat model of tetrachloride carbon (CCl4) mediated liver to adhere to HeLa cells and decreased the proteolytic activity of the injury as judged from serum marker enzyme activities. These cultures parasite’s cysteine proteinases. This was associated with the decreased were treated with CCl4 and extracts of Sapindus mukorossi & Rheum expression of adhesin AP65 and membrane-expressed cysteine proteinase emodi. A protective activity could be demonstrated in the CCl4 damaged TvCP2 genes. Saponins produced no adverse effect on host cells in the primary monolayer culture. For the in vivo study, the hepatoprotective mitochondrial reduction potential measurement assay. Saponin disrupts capacity of the extract of the fruit pericarp of S. mukorossi and the the actin cytoskeleton network beneath the cell membrane and affects rhizomes of Rheum emodi was analyzed in liver injured CCl4- treated membrane-mediated adherence of Trichomonas to the host cells. male rats. Extracts of the fruit pericarp of Sapindus mukorossi (2.5 mg/ mL) and rhizomes of Rheum emodi (3.0 mg/mL) were found to have

5. Anti-cancer activity: Due to the great variability in saponin protective properties in rats with CCl4 induced liver damage as judged structure, saponins always display anti-tumorigenic effect through from serum marker enzyme activities. Thus, it was concluded that the varieties of anti-tumor pathways. There are more than 11 distinguished extracts of Sapindus mukorossi and Rheum emodi do have a protective classes of saponins including , tirucallanes, lupanes, capacity both in vitro on primary hepatocytes cultures and in in vivo in , , taraxasteranes, ursanes, cycloartanes, lanostanes, a rat model of CCl4 mediated liver injury. cucurbitanes and . , belonging to dammaranes, have been found beneficial in the inhibition of tumor angiogenesis by 7. Anxiolytic activity: Methanolic extracts of Sapindus mukorossi suppressing its inducer in the endothelial cells of blood vessels, and then (200 and 40 mg/L) show significant anxiolytic activity as compared to in the prevention of adhering, invasion and metastasis of tumor cells22. standard anxiolytics Diazepam (2 mg/Kg) and Fluoxetine (10 mg/Kg)1.

277 UPADHYAY, A. & SINGH, D.K. - Pharmacological effects of Sapindus mukorossi. Rev. Inst. Med. Trop. Sao Paulo, 54(5): 273-80, 2012.

hederagenin 3-O-(3,4-O-di-acetyl-β-D-xylopyranosyl)-(1→3)-α-L- rhamnopyranosyl-(1→2)-α-L-arabinopyranoside [5], hederagenin 3-O-β-D-xylopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→2)-α-L- arabinopyranoside [6], and hederagenin 3-O-α-L-arabinopyranoside [7]. The bioassay data revealed that 1-7 were molluscicidal, causing 70-100% mortality at 10 ppm against the golden apple snail16.

UPADHYAY & SINGH42 reported that Sapindus mukorossi fruit pericarp is a potential source of botanical molluscicides against Lymnaea acuminata. These snails are the intermediate host of liver flukeFasciola gigantica, which causes 94% fascioliasis in the buffalo population of northern India32. The active molluscicidal component of Sapindus mukorossi fruit is soluble in chloroform, ether, acetone and ethanol. The toxicity of ethanolic extract of Sapindus mukorossi fruit powder

Fig R1 R2 is higher than other extracts which indicates that the molluscicidal 25 Ara -Rha -Ara -OAC H component present is more soluble in ethanol than other organic solvents. 2 3 3 UPADHYAY & SINGH42 characterized that saponin is the active 26 Ara -Rha -Rha -OAC H 2 3 4 component present in Sapindus mukorossi fruit by High Performance 2-OAC Liquid Chromatography. A comparison of the molluscicidal activity of 27 Ara2-Rha3-Xyl H the column-purified fraction ofSapindus mukorossi fruit powder with 3-OAC synthetic molluscicides clearly demonstrates that the purified fraction 2-OAC of Sapindus mukorossi is more potent. The LC50 at 96 h of the column– 28 Ara -Rha -Xyl H purified fraction ofSapindus mukorossi fruit powder (5.43 mg/L) against 2 3 Lymnaea acuminata is lower than those of synthetic molluscicides- 4-OAC carbaryl (14.40 mg/L), phorate (15.0 mg/L), formothion (8.56 mg/L) and 3-OAC 32 niclosamide (11.8 mg/L) . LC50 at 96 h of crude powder of Sapindus 29 Ara2-Rha3-Xy H mukorossi (119.57 mg/L) against Lymnaea acuminata is lower than the 4-OAC crude powder of Canna indica root (359.02 mg/L)40, Thuja orientalis powder (250.55 mg/L), Thuja orientalis fruit powder (255.12 30 Ara2-Rha3-Xyl4-OAC H mg/L)31, Zingiber officinalerhizome (273.80 mg/L), Allium cepa bulb 31 Ara -Rha -Xyl Glc -Glc 2 3 2 (253.27 mg/L)34. 32 Ara2-Rha3-Xyl Glc2-Glc

33 Ara2-Rha Glc2-Glc 9. Tyrosinase inhibition and free radical scavenging: CHEN 2 34 Ara2-Rha H et al. first evaluated that the extracts of Sapindus mukorossi seeds

35 Ara2-Rha3-Xyl H using methanol (MeOH), ethyl acetate (EA) or hexane as solvents 36 Ara -Rha -Xyl -Glc H show tyrosinase inhibition, free radical scavenging, antimicrobial and 2 3 4 anticancer properties. Sapindus mukorossi extracts showed strong specific 6-Rha inhibition activities on the proliferation of human melanoma and lung 37 Ara2-Rha3-Xyl4-Glc H cell lines. The data exhibited the high potential of applying Sapindus 2-Glc mukorossi extracts in medical cosmetology, food supplementation, 6-Rha antibiotics and chemotherapy.

38 Ara2-Rha3-Xyl Ara2-Rha3-Xyl4-Glc 2-Glc 10. Fungicidal activity: The crude extract of Sapindus mukorossi exhibits a strong growth inhibition against the pathogenic yeast Candida albicans, which causes cutaneous candidiasis. Extracts from the dried 8. Molluscicidal activity: Extracts of Sapindus mukorossi showed pericarp of Sapindus L. (Sapindaceae) fruits were investigated for their molluscicidal effect against the golden apple snail, Pomacea canaliculata antifungal activity against clinical isolates of yeasts Candida albicans

Lamarck. (Ampullariidae) with LC50 values of 85, 22 and 17 ppm and Candida non-albicans from vaginal secretions of women with at 24, 48 and 72h exposure period, respectively16. Bioassay-directed Vulvovaginal Candidiasis. Four clinical isolates of C. albicans, a single fractionation of Sapindus mukorossi resulted in the isolation of one clinical isolate of each of the species C. parapsilosis, C. glabrata, C. new hederagenin-based acetylated saponin, hederagenin 3-O-(2,4-O-di- tropicalis, and the strain of C. albicans ATCC 90028 were used. The acetyl-α-l-arabinopyranoside)-(1→3)-α-L-rhamnopyranosyl-(1→2)-α- hydroalcoholic extract was bioactivity-directed against a clinical isolate L-arabinopyranoside [1], along with six known hederagenin saponins, of C. parapsilosis, and showed strong activity. The n-BuOH extract and hederagenin 3-O-(3,4-O-di-acetyl-α-L-arabinopyranoside)-(1→3)-α-L- one fraction showed strong activity against all isolates tested41. The rhamnopyranosyl-(1→2)-α-L-arabinopyranoside [2], hederagenin 3-O-(3- saponin fraction inhibited the dermatophytic fungi Trichophyton rubrum, O-acetyl-β-D-xylopyranosyl)-(1→3)-α-L-rhamnopyranosyl-(1→2)-α-L- Trichophyton mentagrophytes, Sabouraudites canis and Epidermophyton arabinopyranoside [3], hederagenin 3-O-(4-O-acetyl-β-D-xylopyranosyl)- floccosum37. (1→3)-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranoside [4],

278 UPADHYAY, A. & SINGH, D.K. - Pharmacological effects of Sapindus mukorossi. Rev. Inst. Med. Trop. Sao Paulo, 54(5): 273-80, 2012.

11. Anti-inflammatory activity: TAKAGI et al.35 reported that crude yield of its different usable parts could be achieved to derive the saponin and hederagenin isolated from Sapindus mukorossi inhibited maximal amount of commodities of a multifarious nature for the the development of carrageen-induced edema in the rat hind paw as welfare of mankind. This plant has been used as traditional medicine well as on granuloma and exudates formations induced by croton oil for various ailments. The earlier reports on chemical investigation and in rats. The effects of these agents on vascular permeability and acetic pharmacological evaluation showed that Sapindus mukorossi contains a acid induced writhing in mice were also examined. Anti-inflammatory number of bio-active novel compounds. As literature illustrates, many activity on carrageenin edema was observed after intraperitoneal and biological and pharmacological activities are shown by fractions of crude oral administration of crude saponin, whilst hederagenin and the other extracts and isolated substances. Furthermore, the detailed chemical agents showed activity only when administered. analysis is required to isolate bio-active constituents from Sapindus mukorossi and to trace out their biological activities. Thus, it can be 12. Piscicidal activity: Effects of Sapindus mukorossi have been concluded that Sapindus mukorossi can play an important role in modern studied on fish. Pericarp ofSapindus mukorossi is the most toxic parts medical system in near future. yielding 100% mortality within 12 hours and mean survival time was found to be 1.18 hours. LD10, LD50, LD100 ranging between 3.5 ppm and RESUMO 10 ppm at 48 hrs and possess high potential for fish eradication.Sapindus mukorossi fruit pericarp can be used as a selective eradicant for horny Efeitos farmacológicos do Sapindus mukorossi fish likeHeteropneustes fossils and channa punctuate44. Sapindus mukorossi é planta medicinal extremamente valiosa 13 Anti-platelet aggregation activity: HUANG and co workers distribuída nas regiões tropical e subtropical da Ásia. O propósito da demonstrated that five new tirucallane type saponins, sapinmusasaponins presente revisão é uma compilação curta da composição fitoquímica e from the galls of Sapindus mukorossi, showed moderate activity in a das propriedades farmacológicas desta árvore que apresenta múltiplos 12-0-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein-Barr virus propósitos. O principal fitoconstituinte isolado e identificado das diferentes early antigen (EBV-EA) activation assay25. partes desta planta são as saponinas triterpenoidais do tipo da oleana, damarana e tiruculana. A estrutura e o nome químico de todos os tipos DISCUSSION de saponinas triterpenoidais encontrados no Sapindus mukorossi estão incluídos nesta revisão. Muitas pesquisas tem sido conduzidas para provar o Sapindus mukorossi is a versatile and exceptionally valuable potencial desta planta como espermaticida, contraceptivo, hépato-protetor, medicinal plant. It is known by such regional names as soapnut, emético, anti-inflamatório e anti-protozoário. A presente revisão exalta soapberry, washnut, reetha and dodan. The phytochemical screening of alguns principais usos farmacológicos do Sapindus mukorossi. the plant extract showed the presence of saponins (10.1%) present in the pericarp of the fruit. The use of Sapindus mukorossi in folk medicine ACKNOWLEDGEMENT worldwide30 is validated by scientific studies that have demonstrated the efficacy of the extracts in various experimental models. Pharmacological One of the authors Aparna Upadhyay is thankful to Department of effects of Sapindus mukorossi have been reported like anti-bacterial19, Science and Technology, New Delhi for financial assistance (Inspire insecticidal12,13,26, spermicidal11,27, anti-trichomonas11,39, anti-tumor22,29,36, Fellowship number- IF10296). hepatoprotective18, anxiolytic1, molluscicidal16,42, fungicidal37,41, anti- inflammatory35 and piscicidal44 activities and are being employed for REFERENCES the treatment of different ailments in the indigenous system of medicine. Although a number of phytochemicals present in Sapindus mukorossi 1. Chakraborty A, Amudha P, Geetha M, Surjit Singh N. Evaluation of anxiolytic activity have been isolated and identified by researchers working in different of methanolic extract of Sapindus mukorossi Gaertn. in mice. Int J Pharm Bio Scie. 2010;1:1-8. laboratories, their pharmacological/biological studies in human welfare has not been studied so far. 2. Chen CY, Kuo PL, Chen YH, Huang JC, Ho ML, Lin RJ, et al. Tyrosinase inhibition, free radical scavenging, antimicroorganism and anticancer proliferation activities of Most of the scientific study is confined to the elaboration of traditional Sapindus mukorossi extracts. J Taiwan Inst Chem Engrs. 2010;41:129. practices of Sapindus mukorossi. There is a long list of saponins present 3. Chirva V, Kintya PK, Sosnovskii VA. Triterpene glycosides of Sapindus mukorossi. in Sapindus mukorossi. It needs individual attention so that they can be V. The structure of sapindoside E. Chem Nat Compounds. 1970;6:440-2. explored in different pharmacological studies. 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26. Rahman SS, Rahman M, Begum SA, Khan MMR, Bhuiyan MH. Investigation of Received: 17 December 2011 Sapindus mukorossi extracts for repellency, insecticidal activity and plant growth Accepted: 21 March 2012 regulatory effect. J Appl Sci Res. 2007;3:95-101.

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