Medicinal significance, pharmacological activities, and analytical aspects of solasodine: A concise report of current scientific literature

Kanika Patel, Ravi B. Singh, Dinesh K. Patel

1G.L.A Institute of Pharmaceutical Research, Mathura, India

2Institute of Pharmacy, Harish Chandra P.G. College, Varanasi-221002, India

3Department of Pharmaceutics, Institute of Technology, Banaras Hindu University, Varanasi-221005, India

Medicinal significance, pharmacological activities, and analytical aspects of solasodine: A concise report of current scientific literature

Kanika Patel1, Ravi B. Singh2, Dinesh K. Patel3*

1G.L.A Institute of Pharmaceutical Research, Mathura, India

2Institute of Pharmacy, Harish Chandra P.G. College, Varanasi-221002, India

3Department of Pharmaceutics, Institute of Technology, Banaras Hindu University, Varanasi-221005, India

Allelopathy

Pharmacological activity

Phytochemical isolation

Review

Solanaceae

Solasodine

Alkaloids are well known phytoconstituents for their diverse pharmacological properties. Alkaloids are found in all plant parts like roots, stems, leaves, flowers, fruits and seeds. Solasodine occurs as an aglycone part of glycoalkloids, which is a nitrogen analogue to sapogenins. Solanaceae family comprises of a number of plants with variety of natural products of medicinal significance mainly steroidal lactones, glycosides, alkaloids and flavanoids. It is a steroidal alkaloid based on a C27 cholestane skeleton. Literature survey reveals that solasodine has diuretic, anticancer, antifungal, cardiotonic, antispermatogenetic, antiandrogenic, immunomodulatory, antipyretic and various effects on central nervous system. Isolation and quantitative determination was achieved by several analytical techniques. Present review highlights the pharmacological activity of solasodine, with its analytical and tissue culture techniques, which may be helpful to the researchers to develop new molecules for the treatment of various disorders in the future.

1. Introduction

Genus Solanum (Solanaceae) is rich in steroidal glycoalkloids, an important group of plant secondary metabolites. These compounds are used as starting material for the synthesis of steroidal drugs. In majority of solanaceous plants, solasodine occurs as aglycone part of glycoalkloids, which is a nitrogen analogue of sapogenins. Solasodine (C27 cholestane skeleton) (Figure 1) can be readily converted to 16-dehydropregnenolone, a key intermediate in the synthesis of steroidal drugs such as progesterone and cortisone[1]. Solasodine is obtained by chemical or microbial hydrolysis of solamargine. It is a potential moiety to be used as a substitute for diosgenin in the semi-synthetic production of steroidal hormones in pharmaceuticals. Therefore, steroidal glycoalkaloid from Solanaceae plants have become increasingly importantas the starting material for the production of steroidal hormones[2]. Various species of Solanum like Solanum khasianum (S. khasianum), Solanum lyratum (S. lyratum), Solanum xanthocarpum (S. xanthocarpum), Solanum nigrum (S. nigrum), Solanum gracile (S. gracile), Solanum tuberosum (S. tuberosum), Solanum laciniatum (S. laciniatum) are being extensively used for the treatment of various ailments like asthma, liver diseases and inflammation in the traditional system of medicine. Glycoalkaloids are nitrogen containing secondary metabolites found in plants belonging to Solanaceae and Liliaceae family. More then 100 different types of glycoalkaloids have been isolated from more than 350 Solanum species[3].

Plant such as S. tuberosum contains glycoalkaloids as the main phytoconstituents along with chaconine and solanine. Glycoalkaloids concentration depends upon species as well as part of plant such as leaf, root, flower and stem. The amount of glycoalkaloids increases due to injury and exposure to light[4]. Glycoalkaloids play key role in defense mechanism of plants against invading microbes. Glycoalkaloids have antimicrobial, insecticidal and fungicidal properties which account for their activityagainst several insects, pests and herbivores. Small quantities of glycoalkaloids are known to improve flavour, but at levels above 200 mg/kg these compounds may impart the bitter taste[5]. Glycoalkaloids exhibited toxicity in living organism at higher concentrations mainly because of their anticholinesterase activity and disruption of cell membranes coupled with some other effects including teratogenicity, embryotoxicity and genotoxicity. Glycoalkaloids toxicity not only depends upon its amount but also on the type of glycoalkaloids[5,6]. Symptoms of glycoalkaloid poisoning includes abdominal pain, vomiting and diarrhea[4]. In contrast, some glycoalkaloids can also have positive effects on plant growth and human diet. They may provide plant protection from damage by insects and fungi, and are reported to elicit anti-inflammatory and anticancer effects in humans[6].

Figure 1. Chemical structure and overview of solasodine.

The steroidal glycoalkaloids are the family of secondary metabolites produced by Solanaceous plants, including potato, tomato and eggplant[7]. Steroidal glycoalkaloids are nitrogen containing compounds which have the C27 skeleton of cholestane and are the product of steroidal biosynthesis pathway[5]. Synthesis of steroidal alkaloids involves glycosylation of the alkamine steroidal skeleton (aglycone) at C-3b to form steroidal glycoalkaloids[8]. Steroidal glycoalkaloids have antimicrobial, insecticidal and fungicidal properties which provide resistance against several insect pests and herbivores[9]. Solasodine is an important phytochemical of Solanaceae plant including S. lyratum Thunberg, which is commonly used in the traditional Chinese medicines in China, Taiwan and Korea. It has been used to regulate immune function and treat allergic responses for generations[10]. Further, it is also used to treat cancer of liver, lung, esophagus and blood, as well as tumours and warts[11-14].

A number of analytical methods like high performance thin-layer chromatography, high-performance liquid chromatography, capillary electrophoresis, gas chromatography have been developed and used for the determination of solasodine from plant materials[15]. Solanaceae family comprises a number of plants widely known for the presence of variety of natural products of medicinal significance mainly steroidal lactones, glycosides, alkaloids and flavanoids. S. nigrum L. a member of the Solanaceae, has a wide range of medicinal application[16]. Literature survey reveals that solasodine has wide range of pharmacological activity such as diuretic, anticancer, antifungal, hepatoprotective, cardiotonic, antispermatogenetic, antiandrogenic, immunomodulatory, antishock, antipyretic and central nervous system related activity[17]. Because of pharmaceutical importance, its isolation and quantitative determination was achieved by several researchers using an array of analytical techniques like spectroscopy, thin layer chromatography, immunostaining usingmonoclonal antibodies, gas chromatography and high performance liquid chromatography and most recently, using non aqueous capillary electrophoresis[1].

2. Pharmacological activities of solasodine

2.1. Antimicrobial activities of solasodine

Antifungal activity of Solasodine was investigated using Saccharomyces cerevisiae GL7 and Prototheca wickerhamii (P. wickerhamii). Solasodine directly or indirectly interfered with the synthesis and function of genetic substance in S. cerevisiae and P. wickerhamii[18]. In another study, solasodine was tested as growth inhibitors of Trypanosoma cruzi in LIT medium using ketoconazole as a positive control[19]. Evaluation of solasodine on larvae of the red flour beetle, Tribolium castaneum, was investigated. Larval growth was inhibited on diets containing solasodin as one component and found that solasodine is inactive[20]. Effect of aqueous suspensions of glycoalkaloids including solasodine on herpes simplex virus Type I in tissue culture was also investigated and found to be inhibited by prior incubation with solasodine[21].

2.2. Anti-inflammatory and antinociceptive activities of solasodine

Solasodine isolated from Solanum trilobatum has been examined for anti-inflammatory activity in acute and chronic inflammatory animal models. Solasodine exerted statistically significant and dose-dependent antiinflammatory activity in carrageenan-induced rat paw oedema. Topical application of solasodine significantly inhibited the ear inflammation induced by multiple applications of tetradecanoyl-phorbol 13-acetate[22]. Solasodine, isolated from the roots of Solanum trilobatum Linn., was tested for antinociceptive activity using several experimental murine models, viz. the writhing, formalin, and hot plate tests. Solasodine exhibited a significant and dose-dependent decrease in the nociception induced by an intraperitoneal injection of acetic acid. Furthermore, the alkaloid produced a significant increase in the reaction time in the hot plate test[23]. LPS-stimulated macrophage as a model of inflammation was used to investigate the antiinflammatory effects of tomatidine and solasodine whereby it was found that tomatidine exhibited a more potent anti-inflammatory effect than solasodine in the tested concentration[24]. The anti-inflammatory effect of solasodine was evaluated in another study and was found to elicit significant anti-inflammatory activity[25].

2.3. Anticancer activities of solasodine

Natural molecules structurally close to diosgenin including solasodine have been tested for their biological activities on human 1547 osteosarcoma cells[26]. In an another study, solasodine has been utilized to determine the role of carbohydrate moiety in the mechanism of apoptosis. The C3 side chain of solasodine contains 4’Rha-Glc-Rha2’, 4’Rha-Glc and H, respectively[27]. In another study, solasodine showed significant cytotoxic effects against human PLC/ PRF/5 cells in vitro[28].

2.4. Antiandrogenic activities of solasodine

Oral administration of solasodine isolated from the berries of the S. xanthocarpum to dogs significantly decreased the epithelial cell height of cauda epididymides. The cells became atrophic and the lumen was devoid of spermatozoa. Castration followed by the adminstration of solasodine further reduced the epithelial cell height in comparison to castrated controls. Total protein, sialic acid, glycogen and acid phosphatase activities were significantly reduced in solasodine treated cauda epididymides. These results suggests the anti-androgenic potency of solasodine[29]. Effect of solasodine derived from solasonine in eggplants was evaluated for their effects on liver weight increase in non-pregnant and pregnant mice and on fecundity in pregnant mice fed for 14 d. In non-pregnant mice, observed ratios of liver weights to body weights were found to be significantly greater in solasodine treated group than the control[30]. Solasodine obtained from the S. xanthocarpum berries was administered to Rhesus monkeys for 150 d to evaluate its effect on testicular cell population dynamics. Solasodine brings about an interference with spermiogenesis at the stage XII of late spermatids. No significant change was found in the population of spermatogonia/primary and secondary spermatocytes. The production of immature and mature Leydig cells was decreased. The testicular protein, sialic acid and glycogen contents were depleted following solasodine treatments to rhesus monkeys[31]. Chronic administration of solasodine caused testicular lesions resulting in a severe impairment of spermatogenic elements. The epididymides were devoid of spermatozoa. Total protein, sialic acid and glycogen contents of the testis and epididymis were reduced significantly whereas the testicular cholesterol was elevated. Solasodine administration in dogs definitely rendered the male infertile as evidenced by the absence of sperms in the cauda epididymis and ductus deferens[32].

2.5. Effect of solasodine on CNS

Effect of solasodine to promote neurogenesis in vitro and in vivo in mouse embryonic teratocarcinoma P19 cells was investigated. In vivo, a 2-week infusion of solasodine into the left ventricle of the rat brain followed by a 3-week washout resulted in a significant increase in bromodeoxyuridine uptake by cells of the ependymal layer, subventricular zone, and cortex that co-localized with doublecortin immunostaining, demonstrating the proliferative and differentiating properties of solasodine on neuronal progenitors[33]. An anticonvulsant and CNS depressant effect of solasodine isolated from S. sisymbriifolium using several experimental models was investigated. The results showed that intraperitoneal injection of solasodine significantly delayed latency of hind limb tonic extensor (HLTE) phase in the PCT-induced convulsions. In the MES model, solasodine significantly reduced duration of HLTE in a dose-dependent manner. Prior treatment of solasodine significantly potentiated thiopental-provoked sleep in a dose-dependent manner[34].

2.6. Effect of solasodine on body temperature

Effect of solasodine from S. laciniatum Ait., was studied on normal and pyretic body temperature of rats and mice. In rats, single dosage depressed the normal temperature for 24 h. With larger dosages or longer treatment the effect could not be intensified and tolerance was also not observed. In mice, the temperature decrease and effect was reproducible by repeated treatment[35].

2.7. Enzyme and other activities of solasodine

UDP-glucose-dependent glucosylation of solasodine and diosgenin by a soluble, partially purified enzyme fraction from eggplant leaves is affected in a markedlydifferent way by some phospholipids. The glucosylation of solasodine is unaffected or slightly stimulated. Significant inhibition of diosgenin glucoside synthesis and stimulation of solasodine glucosylation was found only with PC molecular species containing fatty acids with chain length of 12-18 carbon atoms[36]. A series of 31 side-chainmodified analogues of steroidal alkaloids solasodine was studied as inhibitors of (S)-adenosyl-L-methionine:delta 24(25)-sterol methyl transferase (SMT) enzyme activity from Saccharomyces cerevisiae[37]. Solasodine, a steroid present in the mucilaginous exotesta of the seed in S. viarum Dunal is a major source of steroidal raw material. Evidence for the site of solasodine synthesis was sought through reciprocal grafts involving steroid-bearing S. viarum (both diploid and autotetraploid) and steroidfree, edible S. melongena L. (brinjal). The results indicate that the synthesis of solasodine is scion-specific[38]. The increase in relative liver weight induced by solanidine and solasodine is a reversible adaptive response. These findings and the apparent effects of structure on biological activity should serve as a guide for the removal of the most toxic compounds from plant foods[39]. Impregnated CD2 transgenic mice, which contain multiple copies of a lambda gt10lacZ construct integrated into the genome of each cell, were given a predetermined estimated maximum tolerated dose of several steroidal alkaloids including solasodine[40]. Embryos of two species of fish Japanese rice fish, medaka (Oryzius latipes) and the rainbow trout (Oncorhynchus mykiss) were also evaluated for their suitability as model systems for steroidal alkaloid toxicity including solasodine[41]. Effect of several potato glycoalkaloids and aglycones in the frog embryo teratogenesis assay--Xenopus (FETAX) with and without metabolic activation by Aroclor 1254-induced rat liver microsomes was investigated. The aglycones solasodine was found to be less toxic than the glycosides[42]. Isolation of the glycosyltransferases that catalyze the transfer of sugar molecules to steroidal compounds will help to clarify the mechanisms that produce diverse saponins and control their activities in plants. Gene expression analysis revealed that the accumulation of SaGT4A transcripts showed a unique response to wounding stress indicating the involvement of SaGT4A in plant defense system[43].

3. Tissue culture techniques

Single chain fragment-variable (scFv) enhanced solasodine glycoside accumulation in S. khasianum hairy root cultures transformed by the ScFv solamargine (As)-scFv gene. The expressed anti-solamargine scFv protein could be useful for determination of total solasodine glycoside content in plant samples by ELISA[44]. In another study using genetic transformation of Agrobacterium rhizogenes and liquid culture, induction and culture conditions for S. nigrum L. var. pauciflorum Liou hairy roots and its solasodine production and consumption changes of N resource and calcium in the medium during liquid culture were investigated. The hairy roots could produce medicinal secondary metabolites solasodine and the amount of solasodine in the hairy root cultures[45]. The role of plant growth regulators and various concentrations of NaCl during in vitro production of solasodine were studied. Solasodine content was maximum in regenerative callus when grown on medium added with 150 mM NaCl; followed by in vitro raised leaf of microshoot[46]. Leaf and hypocotyl explants of 15 d old aseptically grown seedlings of S. laciniatum were cultured on MS medium supplemented with NAA and kinetin for callus initiation. The solasodine content in callus culture was maximum after 30 d of incubation. Organogenesis promoted solasodine accumulation in the cultures. Regenerated shoots yielded higher solasodine content than undifferentiated as well as organogenic callus[47].

Hairy root cultures of Physalis minima L. were developed using Agrobacterium rhizogenes, strain ATCC 15834 mediated transformation and grown in half strength of Murashige and Skoog medium containing sucrose. Media supplementation with naphthalenacetic acid and benzyladenine increased solasodine glycoside which was 20 times higher than that in the native root[48]. Hairy root clones of S. aviculare which were transgenic for hmgr typically grew faster than those which did not contain extra copies of this gene and also accumulated up to 4.2 times more solasodine when grown under dark, but not light conditions[49]. The effect of a fungal elicitor obtained from Alternaria sp. on growth and solasodine production by free and alginateentrapped cells of S. eleagnifolium Cav. was studied. The solasodine production increased in suspension cultures and in entrapped cells. In both cases, about 50%-60% of intracellular solasodine was released into the medium[50]. Procedures were developed for ‘self-immobilisation’of S. aviculare cells to eliminate the need for artificial immobilisation supports. Most of the product was stored in the aggregates to reach a maximum concentration of 0.3% dry weight; this is between 1.5 and 10 times the levels reported for suspended cells under similar conditions. A substantial amount of solasodine was produced after growth ceased. A simple air-driven bioreactor was tested for culture of the aggregates; solasodine yields were comparable to those measured in shake flasks[51].

4. Analytical methods to identify and isolate solasodine

The mass fragmentations of solasodine were studied using the Orbitrap Fourier transform (FT) mass spectrometer[52]. The development of sequential injection analysis with lab-at-valve semi-automated system on-line liquidliquid extraction is demonstrated for spectrophotometric determination of solasodine in various Solanum species fruits. The method performances, including reproducibility, linearity, sensitivity and accuracy were also evaluated[53]. Quantitative estimation of solasodine was carried out using a novel HPTLC method, which is validated for its recovery and precession. The proposed HPTLC method showed agood linear relationship in the concentration ranges[46]. A prechromatographic derivatization of solasodine was done by forming an ion-pair complex of the heterocyclic nitrogen using the acidic dye methyl orange and acetate buffer of pH 4.7. Detection could be made in the visible range at 530 nm in this method. The method has good reproducibility and was found to be suitable for estimation of solasodine[54]. Concomitant extraction and hydrolysis of Solanum steroidal glycoalkaloids in a two-phase system containing an aqueous mineral acid and an organic water immiscible solvent, and having a boiling point under 100 °C is described. Application of the process to fruits, leaves, and tissue cultures of Solanum khasianum using a two-phase aqueous hydrochloric acid-toluene system, proved to be very suitable for continuous production of pure solasodine which is a valuable raw steroid for the preparation of steroidal drugs[55].

Nonaqueous capillary electrophoresis coupled to UV detection is described for the separation and determination of steroidal alkaloids. After optimization of electrophoretic parameters, including the electrolyte nature and the organic solvent composition, a reliable separation of solasodine and solanidine was achieved in a methanolacetonitrile (20:80, v/v) mixture containing 25 mM ammonium acetate and 1 M acetic acid[56]. GC-MS analysis of hydrolysates of purified extracts of the test Solanum species revealed that solasodine was a principal or sole aglycone of the alkaloid glycosides in each of the test species except S. tuberosum[57]. Glycoalkaloids were extracted from plant material of S. Sodomaeum L. Highperformance liquid chromatographic studies indicated that several glycoalkaloids were present. Mass spectral analyses showed that all the glycoalkaloids contained solasodine[58]. A potentiometric nonaqueous titration procedure was developed for the quantitative determination of solasodine in fruits of the Solanum species[59]. In another study solasodine has been isolated from S. platanifolium[60]. The fresh bulbs of Lilium brownii var. colchesteri were found to contain five steroidal saponins including solasodine along with several phenolic constituents[61]. High-pressure liquid chromatography was used to separate the steroidal alkaloids including solasodine. The method was used to prepare crystalline solanidine from a crude mixture of aglycones obtained from S. chacoense, and to separate radioactive solanidine from extracts of potato plants fed with (4-C) cholesterol[62]. A combined derivatization method for gas chromatographic-mass spectrometric (GC-MS) analysis of steroidal glycoalkaloid including solasodine was developed using both trimethylsilylation and pentafluoropropionylation[63].

5. Conclusion

Herbal medicines are used for the treatment of various disorders and gaining popularity both in developing and developed countries due to its fewer side effects. Many traditional medicines are derived from medicinal plants, minerals and organic matter. According to the World Health Organization (WHO) more than 21 000 plants are used for medicinal purposes in the world[64-66]. Due to presence of diverse phytoconstituents, many medicinal plants have excellent pharmacological actions and could lead to the development of new classes of possibly safer agents for the treatment of disease. Plants have been used as a source of drugs, and many of the currently available drugs have been derived directly or indirectly from them[67].

Several medicinal plants have been used as dietary supplements and in the treatment of numerous diseases without proper knowledge of their mode of action. Only a few herbs and bioactive chemical moiety have attracted the interest of scientists and have been put forward for investigations. Therefore, there is a need of more welldocumented clinical trials and more laboratory work to justify their pharmacological actions and toxicity for safe and effective treatment[68,69]. Solasodine may have all these actions and could be used for the treatment of various complications in the near future. The present review comprises updated information regarding pharmacological activity and analytical techniques of solasodine. Moreover tissue culture techniques on solasodine have been also discussed. The overall information provided in the present review article may prove as an important source of information to the researchers in the research area of natural product.

Conflict of interest

The authors declare they have no conflict of interests.

[1] Pawar Pankaj K, Borse Tushar P, Pinjari Rizwan Z, Maheshwari Vijay L. A simple technique for rapid quantitative determination of solasodine from cultured hairy roots of Solanum surattense. J Herb Med Toxicol 2008; 2(1): 7-10.

[2] Solouki M, Hoshyar H, Ramroudi M, Tavassoli A. Comparison and evaluation of steroid alkaloid solasodine on in vivo and in vitro cultures of Solanum surattense Burm L. Afr J Microbiol Res 2011; 5(23): 3981-3985.

[3] Sun F, Li S, He D, Cao G, Ni X, Tai G, et al. Effects of glycoalkaloids from Solanum plants on cucumber root growth. Phytochemistry 2010; 71(13): 1534-1538.

[4] Arnqvist L, Dutta PC, Jonsson L, Sitbon F. Reduction of cholesterol and glycoalkaloid levels in transgenic potato plants by overexpression of a type 1 sterol methyltransferase cDNA1. Plant Physiol 2003; 131(4): 1792-1799.

[5] Nema PK, Ramayy N, Duncan E, Niranjan K. Potato glycoalkaloids: formation and strategies for mitigation. J SciFood Agric 2008; 88(11): 1869-1881.

[6] Carputo D, Savarese S, Andolfi A, Aversano R, Cimmino A, Frusciante L, et al. Glycoalkaloid profile in potato haploids derived from Solanum tuberosum-S. bulbocastanum somatic hybrids. Chem Biodivers 2010; 7(8): 1885-1892.

[7] Kent FM, Louise VT, Paul VA, Malendia MM, David RR, Dennis LC, et al. Metabolic compensation of steroidal glycoalkaloid biosynthesis in transgenic potato tubers: using reverse genetics to confirm the in vivo enzyme function of a steroidal alkaloid galactosyltransferase. Plant Sci 2004; 168(1): 267-273.

[8] Itkin M, Rogachev I, Alkan N, Rosenberg T, Malitsky S, Masini L, et al. Glycoalkaloid metabolism is required for steroidal alkaloid glycosylation and prevention of phytotoxicity in tomato. Plant Cell 2011; 23(12): 4507-4525.

[9] Rodriguez-Saona LE, Wrolstad RE, Pereira C. Glycoalkaloid content and anthocyanin stability to alkaline treatment of redfleshed potato extracts. J Food Sci 1999; 64(3): 445-450.

[10] Kang B, Lee E, Hong I, Lee J, Kim H. Abolition of anaphylactic shock by Solanum lyratum Thunb. Int J Immunopharmacol 1997; 19(11-12): 729-734.

[11] Yalin W, Yuanjiang P, Cuirong S. Isolation, purification and structural investigation of a water-soluble polysaccharide from Solanum lyratum Thunb. Int J Biol Macromol 2005; 36(4): 241-245.

[12] Sun LX, Fu WW, Li W, Bi KS, Wang MW. Diosgenin glucuronides from Solanum lyratum and their cytotoxicity against tumor cell lines. Z Naturforsch C 2006; 61(3-4): 171-176.

[13] Ren J, Feng GN, Wang MW, Sun LX. Primary study on the anti-tumor effect of ethanol extracts of Solanum lyratum. Zhongguo Zhong Yao Za Zhi 2006; 31(6): 497-500.

[14] Kuo WW, Huang CY, Chung JG, Yang SF, Tsai KL, Chiu TH, et al. Crude extracts of Solanum lyratum protect endothelial cells against oxidized low-density lipoprotein-induced injury by direct antioxidant action. J Vasc Surg 2009; 50(4): 849-860.

[15] Trivedi P, Pundarikakshudu K. Novel TLC densitometric method for quantification of solasodine in various Solanum species, market samples and formulations. Chromatographia 2007; 65(3/4): 239-243.

[16] Yogananth N, Bhakyaraj R, Chanthuru A, Parvathi S, Palanivel S. comparative analysis of solasodine from in vitro and in vivo cultures of Solanum nigrum linn. Kathmandu Univ J Sci Eng Technol 2009; 5(1): 99-103.

[17] Desai AB, Kagathara VG, Joshi H, Rangani AT, Mungra H. Evaluation of antiamnesic effect of solasodine in mice. Int J Pharm Tech Res 2011; 3(2): 732-740.

[18] Wang LD, Guo DA, Yuan L, He QH, Hu YQ, Tu PF, et al. Antifungal effect of three natural products on the genetic substance of Saccharomyces cerevisiae GL7 and Prototheca wickerhamii. Yao Xue Xue Bao 2000; 35(11): 860-863.

[19] Chataing B, Concepción JL, Lobatón R, Usubillaga A. Inhibition of Trypanosoma cruzi growth in vitro by Solanum alkaloids: a comparison with ketoconazole. Planta Med 1998; 64(1): 31-36.

[20] Weissenberg M, Levy A, Svoboda JA, Ishaaya I. The effect of some Solanum steroidal alkaloids and glycoalkaloids on larvae of the red flour beetle, Tribolium castaneum, and the tobacco hornworm, Manduca sexta. Phytochemistry 1998; 47(2): 203-209.

[21] Thorne HV, Clarke GF, Skuce R. The inactivation of herpes simplex virus by some Solanaceae glycoalkaloids. Antiviral Res 1985; 5(6): 335-343.

[22] Pandurangan A, Khosa RL, Hemalatha S. Anti-inflammatory activity of an alkaloid from Solanum trilobatum on acute and chronic inflammation models. Nat Prod Res 2011; 25(12): 1132-1141.

[23] Pandurangan A, Khosa RL, Hemalatha S. Antinociceptive activity of steroid alkaloids isolated from Solanum trilobatum Linn. J Asian Nat Prod Res 2010; 12(8): 691-695.

[24] Chiu FL, Lin JK. Tomatidine inhibits iNOS and COX-2 through suppression of NF-kappaB and JNK pathways in LPS-stimulated mouse macrophages. FEBS Lett 2008; 582(16): 2407-2412.

[25] Emmanuel S, Ignacimuthu S, Perumalsamy R, Amalraj T. Antiinflammatory activity of Solanum trilobatum. Fitoterapia 2006; 77(7-8): 611-612.

[26] Trouillas P, Corbière C, Liagre B, Duroux JL, Beneytout JL. Structure-function relationship for saponin effects on cell cycle arrest and apoptosis in the human 1547 osteosarcoma cells: a molecular modelling approach of natural molecules structurally close to diosgenin. Bioorg Med Chem 2005; 13(4): 1141-1149.

[27] Chang LC, Tsai TR, Wang JJ, Lin CN, Kuo KW. The rhamnose moiety of solamargine plays a crucial role in triggering cell death by apoptosis. Biochem Biophys Res Commun 1998; 242(1): 21-25.

[28] Lin CN, Lu CM, Cheng MK, Gan KH, Won SJ. The cytotoxic principles of Solanum incanum. J Nat Prod 1990; 53(2): 513-516.

[29] Gupta RS, Dixit VP. Effects of short-term treatment of solasodine on cauda epididymis in dogs. Indian J Exp Biol 2002; 40(2): 169-173.

[30] Friedman M, Henika PR, Mackey BE. Effect of feeding solanidine, solasodine and tomatidine to non-pregnant and pregnant mice. Food Chem Toxicol 2003; 41(1): 61-71.

[31] Dixit VP, Gupta RS, Gupta S. Antifertility plant products: testicular cell population dynamicsfollowing solasodine (C27H43O2N) administration in rhesus monkey (Macaca mulatta). Andrologia 1989; 21(6): 542-546.

[32] Dixit VP, Gupta RS. Antispermatogenic/antiandrogenic properties of solasodine (C27H43O2N) obtained from Solanum xanthocarpum berries on the male genital tract of dog (Canisfamiliaris). A histophysiological approach. Int J Androl 1982; 5(3): 295-307.

[33] Lecanu L, Hashim AI, McCourty A, Giscos-Douriez I, Dinca I, Yao W, et al. The naturally occurring steroid solasodine induces neurogenesis in vitro and in vivo. Neuroscience 2011; 183: 251-264.

[34] Chauhan K, Sheth N, Ranpariya V, Parmar S. Anticonvulsant activity of solasodine isolated from Solanum sisymbriifolium fruits in rodents. Pharm Biol 2011; 49(2): 194-199.

[35] Kulcsár-Gergely J. The effect of solasodine on the body temperature. Arzneimittelforschung 1976; 26(1): 55-57.

[36] Pazkowski C, Kalinowska M, Wojciechowski ZA. Phospholipidsmodulate the substrate specificity of soluble UDP-glucose: steroid glucosyltransferase from eggplant leaves. Phytochemistry 2001; 58(5): 663-669.

[37] Nes WD, Guo D, Zhou W. Substrate-based inhibitors of the (S)-adenosyl-L-methionine: delta24 (25) - to delta24 (28)-sterol methyl transferase from Saccharomyces cerevisiae. Arch Biochem Biophys 1997; 342(1): 68-81.

[38] Srinivas M, Krishnan R. Effect of grafting on solasodine content in Solanum viarum. Planta Med 1996; 62(4): 360-361.

[39] Friedman M, Henika PR, Mackey BE. Feeding of potato, tomato and eggplant alkaloids affects food consumption and body and liver weights in mice. J Nutr 1996; 126(4): 989-999.

[40] Crawford L, Myhr B. A preliminary assessment of the toxic and mutagenic potential of steroidal alkaloids in transgenic mice. Food Chem Toxicol 1995; 33(3): 191-194.

[41] Crawford L, Kocan RM. Steroidal alkaloid toxicity to fish embryos. Toxicol Lett 1993; 66(2): 175-181.

[42] Friedman M, Rayburn JR, Bantle JA. Developmental toxicology of potato alkaloids in the frog embryo teratogenesis assay--Xenopus (FETAX). Food Chem Toxicol 1991 29(8): 537-547.

[43] Kohara A, Nakajima C, Hashimoto K, Ikenaga T, Tanaka H, Shoyama Y, et al. A novel glucosyltransferase involved in steroid saponin biosynthesis in Solanum aculeatissimum. Plant Mol Biol 2005; 57(2): 225-239.

[44] Putalun W. Technology of compact MAb and its application for medicinal plant breeding named as missile type molecular breeding. Curr Drug Discov Technol 2011; 8(1): 24-31.

[45] Wu XF, Shi HP, Tsang P, Keung E. Induction and in vitro culture of hairy roots of Solanum nigrum L. var. pauciflorum Liou and its solasodine production. Fen Zi Xi Bao Sheng Wu Xue Bao 2008; 41(3): 183-191.

[46] Bhat MA, Ahmad S, Aslam J, Mujib A, Mahmooduzzfar. Salinity stress enhances production of solasodine in Solanum nigrum L. Chem Pharm Bull 2008; 56(1): 17-21.

[47] Bhatnagar P, Bhatnagar M, Nath AK, Sharma DR. Production of solasodine by Solanum laciniatum using plant tissue culture technique. Indian J Exp Biol 2004; 42(10): 1020-1023.

[48] Putalun W, Prasamsiwamai P, Tanaka H, Shoyama Y. Solasodine glycoside production by hairy root cultures of Physalis minima Linn. Biotechnol Lett 2004; 26(7): 545-548.

[49] Argôlo AC, Charlwood BV, Pletsch M. The regulation of solasodine production by Agrobacterium rhizogenes-transformed roots of Solanum aviculare. Planta Med 2000; 66(5): 448-451.

[50] Quadri LE, Giulietti AM. Effect of elicitation on the accumulation of solasodine by immobilized cells of Solanum eleagnifolium Cav. Enzyme Microb Technol 1993; 15(12): 1074-1077.

[51] Tsoulpha P, Doran PM. Solasodine production from selfimmobilised Solanum aviculare cells. J Biotechnol 1991; 19(1): 99-110.

[52] Cahill MG, Caprioli G, Vittori S, James KJ. Elucidation of the mass fragmentation pathways of potato glycoalkaloids and aglycons using Orbitrap mass spectrometry. J Mass Spectrom 2010; 45(9): 1019-1025.

[53] Thongchai W, Liawruangrath B, Liawruangrath S. Sequential injection analysis with lab-at-valve (SI-LAV) for the determination of solasodine in Solanum species. Talanta 2010; 81(1-2): 565-571.

[54] Trivedi PD, Patel BC, Rathnam S, Pundarikakshudu K. A validated liquid chromatographic method for estimation of solasodine in various Solanum species and market formulations. J AOAC Int 2006; 89(6): 1519-1523.

[55] Weissenberg M. Isolation of solasodine and other steroidal alkaloids and sapogenins by direct hydrolysis-extraction of Solanum plants or glycosides therefrom. Phytochemistry 2001; 58(3): 501-508.

[56] Cherkaoui S, Bekkouche K, Christen P, Veuthey JL. Nonaqueous capillary electrophoresis with diode array and electrospray mass spectrometric detection for the analysis of selected steroidal alkaloids in plant extracts. J Chromatogr A 2001; 922(1-2): 321-328.

[57] Keeler RF, Baker DC, Gaffield W. Spirosolane-containing Solanum species and induction of congenital craniofacial malformations. Toxicon 1990; 28(8): 873-884.

[58] Cham BE, Wilson L. HPLC of Glycoalkaloids from Solanum sodomaeum. Planta Med 1987; 53(1): 59-62.

[59] Telek L. Determination of solasodine in fruits of Solanum species. J Pharm Sci 1977; 66(5): 699-702.

[60] Puri R, Wong TC, Puri RK.1H- and13C-nmr assignments and structural determination of a novel glycoalkaloid from Solanum platanifolium. J Nat Prod 1994; 57(5): 587-596.

[61] Mimaki Y, Sashida Y. Steroidal saponins and alkaloids from the bulbs of Lilium brownii var. colchesteri. Chem Pharm Bull 1990; 38(11): 3055-3059.

[62] Hunter IR, Walden MK, Wagner JR, Heftmann E. Highpressure liquid chromatography of steroidal alkaloids. J Chromatogr 1976; 28(119): 223-226.

[63] Laurila J, Laakso I, Väänänen T, Kuronen P, Huopalahti R, Pehu E. Determination of solanidine- and tomatidinetype glycoalkaloid aglycons by gas Chromatography/Mass spectrometry. J Agric Food Chem 1999; 47(7): 2738-2742.

[64] Modak M, Dixit P, Londhe J, Ghaskadbi S, Devasagayam TPA. Indian herbs and herbal drugs used for the treatment of diabetes. J Clin Biochem Nutr 2007; 40: 163-173.

[65] Patel DK, Kumar R, Prasad SK, Hemalatha S. Pharmacologically screened aphrodisiac plant-A review of current scientific literature. Asian Pac J Trop Biomed 2011; 1(1): S131-S138.

[66] Patel DK, Laloo D, Kumar R, Hemalatha S. Pedalium murex Linn-An overview of its phytopharmacological aspects. Asian Pac J Trop Med 2011; 4: 748-755.

[67] Patel DK, Prasad SK, Kumar R, Hemalatha S. Cataract: A major secondary complication of diabetes, its epidemiology and an overview on major medicinal plants screened for anticatract activity. Asian Pac J Trop Dis 2011; 1: 323-329.

[68] Patel DK, Prasad SK, Kumar R, Hemalatha S. An overview on antidiabetic medicinal plants having insulin mimetics property. Asian Pac J Trop Biomed 2012; 2: 320-330.

[69] Patel DK, Kumar R, Laloo D, Hemalatha S. Diabetes mellitus: An overview on its pharmacological aspects and reported medicinal plants having andiabetic activity. Asian Pac J Trop Biomed 2012; 2: 411-442.

5 March 2013

*Corresponding author: Dinesh K. Patel, Department of Pharmaceutics, Institute of Technology, Banaras Hindu University, Varanasi-221005, India.

Tel: +91 9919192440

E-mail: dkpatel.rs.phe@itbhu.ac.in

ARTICLE INFO

Article history:

Received in revised form 24 March 2013

Accepted 20 May 2013

Available online 20 June 2013