STIGMASTEROL: A COMPREHENSIVE REVIEWHTML Full Text
STIGMASTEROL: A COMPREHENSIVE REVIEW
Navpreet Kaur, Jasmine Chaudhary*, Akash Jain and Lalit Kishore
- M. College of Pharmacy, M.M. University, Mullana, Ambala, Haryana- 133207, India
Extensive research has been carried out from last decades to discover potential constituents from plant sources. Stigmasterol is an important constituent and has been isolated from plants. It is involved in the synthesis of many hormones like progesterone, androgens, estrogens and corticoids. In addition to stigmasterol many of its derivatives like, spinasterol, fucosterol, cyasterone, stigmasterol glucoside, fucosterol epoxide, stigma-4en-3one, 29-fluorostigmasterol etc. have been isolated and their pharmacological aspects has been assessed. This comprehensive account provides information about stigmasterol and its derivatives. The diversity in their pharmacological reports reveals that this constituent is worth further investigation.
INTRODUCTION: Stigmasterol, also known as Stigmasterin or Wulzen anti-stiffness factor (Figure 1), an unsaturated plant sterol present in various medicinal plants. Stigmasterol is utilized in a number of chemical processes which are designed to yield numerous synthetic and semi-synthetic compounds for pharmaceutical industry. It acts as a precursor in the synthesis of progesterone and acts as an intermediate in the biosynthesis of androgens, estrogens, corticoids 1 and in the synthesis of vitamin D3 2.
- FIG. 1: STRUCTURE OF STIGMASTEROLIt was first isolated in Calabarbohne in 1906 by Adolf Wind Form and A. Hauth 3. Further, it has been isolated from various medicinal herbs like Croton sublyratus 4, Ficus hirta 5, Eclipta alba (L.) Hassk 6, Eclipta prostrate 7, Parkia speciosa 8, Gypsophila oldhamiana 9, Eucalyptus globules 10, Aralia cordata 11, Emilia sonchifolia 12, Akebia quinata 13, Desmodium styracifolium 14, Heracleum rapula 15 etc.Stigmasterol has been investigated for its pharmacological prospects such as antiosteoarthritic, antihypercholestrolemic, cytotoxicity, antitumor, hypoglycaemic, antimutagenic, antioxidant, anti-inflammatory and CNS effects.Chemistry: Stigmasterol is chemically, (3S, 8S, 9S, 10R, 13R, 14S, 17R)-17-[(E, 2R, 5S)-5-ethyl-6-methylhept-3-en-2-yl]-10, 13-dimethyl-2, 3, 4, 7, 8, 9, 11, 12, 14, 15, 16, 17-dodecahydro-1Hcyclopenta[a]phenanthren-3-ol has been isolated and its presence was confirmed by performing some reactions like Salkowski and Liebermann Burchard reaction 16 and structure of stigmasterol was elucidated by IR and NMR. As it is non-polar in nature, it is isolated from various parts of the plants by extracting with solvents which are higher in the ellutropic series i.e., non-polar solvents only.It has been found in the petroleum ether extract of aerial parts of Ageratum conyzoides (Asteraceae) 17, Calotropis gigantean 18, root and aerial part of Desmodium gangeticum 19, seeds of Terminalia chebula 20, petroleum ether extract of aerial parts of Byrophyllum pinnatum 21, petroleum ether extract of woody stem of Abelmoschus manihot 22, hexane extract of leaves of Pandanus amaryllifolius 23.Biosynthesis of phytosterol from mevalonate and deoxy-xylulose pathway was investigated in the callus culture of Croton sublyratus from the leaf explants. It was found that biosynthesis was active during the linear phase of the culture and both pathways contribute equally. Feeding of [1-13C] glucose into the callus culture at this growth phase showed that the label from glucose was highly incorporated into both phytosterols. Isolation of the labelled products followed by 13C NMR analysis revealed that the phytosterols had their 13C-labeling patterns consistent with the acquisition of isoprene units via both the mevalonate pathway and the deoxy-xylulose pathway with relatively equal contribution. Since the biosynthesis of phytosterol has so far been reported to be mainly from the classical mevalonate pathway, this study provides new evidence on the biosynthesis of phytosterols via the novel deoxy-xylulose pathway 4. Diagrammatic representation of the pathway is shown in Figure 2.
- FIG. 2: DIAGRAMMATIC REPRESENTATION OF BIOSYNTHETIC PATHWAY OF STIGMASTEROL IN CROTON SUBLYRATUS Apart from stigmasterol a number of its derivatives have also been isolated from plants and their pharmacological aspects evaluated. These derivatives along with their pharmacological activities are listed in Table 1 and their structures are shown in Figure 3.
TABLE 1: DERIVATIVES OF STIGMASTEROL AND THEIR PHARMACOLOGICAL ACTIVITIES
Derivative Pharmacological Activity Reference Cyasterone Anti feeding 24 Courgeon AM (1972) 25 Fucosterol Antioxidant,26 Antidiabetic 27 Minale L, et al. (1977) 28 Foetidin Hypoglycaemic Marguis VO (1977) 29 Stigmast-5-ene-3 beta, 28-diol --- Nicotra F (1979) 30 Stigmast-5-en-3 beta, 24-diol --- Nicotra F (1979) 30 Fucosterol epoxide Insecticide 31 Fujimoto Y (1980) 32 Spinasterol Anti-tumour 33 Yasukawa K (1981) 34 29-fluorostigmasterol Insecticide Prestwich GD (1984) 35 Stigmasterol-24,28-epoxide --- Svoboda JA (1989) 36 Dehydrooogoniol Female activating hormone 37 Svoboda JA (1989) 36 3-O-(6'-O-palmitoylglucosyl)stigmasta-5, 25(27)-diene Antimutagen Guevara AP (1990) 38 3-O-(6'-O-stearoylglucosyl)stigmasta-5, 25(27)-diene Antimutagen Guevara AP (1990) 38 3-hydroxystigmast-5-en-7-one Anticomplementary Ebihara T (1991) 39 22, 23-dihydrospinasterone --- Ding L (1991) 40 6-chlorostigmasterol --- Chen WX (1993) 41 Stigmasta-5, 22-dien-3-ol --- Ruan J (2001) 42 Stigmasterol glucoside Neurotoxic Khabazian I, et al. (2002)43 12-hydroxystigmast-4-en-3-one Cytotoxic Chowdhary R (2003) 44 (24R)stigmast-1, 5-dien-3 beta-ol Antioxidant, antimicrobial 45 Ali A (2003) 46 Stigmast-4-en-3-one Hypoglycaemic Alexander-Lindo RL (2004) 47
Figure 3: Structures of derivatives of stigmasterol.
PHARMACOLOGICAL STUDIES OF STIGMASTEROL
Anti-osteoarthritic activity: Stigmasterol was investigated by Gabay O, for its antiosteoarthritic activity. Newborn mouse chondrocytes and human osteoarthritis chondrocytes were incubated for 18 hour with or without IL-1β. Then these cells were incubated for 48 hour with stigmasterol and the results were compared to the untreated cells. Expression of various genes involved in the cartilage turn over, MMP-3, MMP-13, and ADAMTS-4, was elevated after treatment with IL-1beta for 18 hour and stigmasterol significantly decrease this effect and hence produces anti-osteoarthritic effect 48.
Anti-hypercholestrolemic activity: It was found by Chandler RF that stigmasterol has significant effect on serum cholesterol comparable with the antihypercholestrolemic activity of β-sitosterol. So, this study concluded that saturation of the side chain, at least at C22 is important for antihypercholestrolemic activity 49. Further, Batta AK found that this plant sterol has been found to compete with cholesterol for intestinal absorption and thus lower the plasma concentration of cholesterol. Stigmasterol was reported to inhibit cholesterol biosynthesis via inhibition of sterol ∆24-reductase in human Caco-2 and HL-60 cell lines thus suppressing hepatic cholesterol 50.
Cytotoxicity: Stigmasterol, the active constituent of Cacalia tangutica, was found to be Cytotoxic to Spodoptera litura cells and its action was more marked in comparison to the other active constituents of the plant namely, friedelin and rotenone 51. Gomez MA stated that stigmasterol in the chloroform extract of Achillea ageratum and its cytostatic activity against Hep-2 and McCoy cells was determined. It showed high degree of inhibition when compared with 6- Mercaptopurine against both cultures 52.
Anti-tumor: Carthami flos contained stigmasterol which markedly inhibited the tumour promotion in the two-stage carcinogenesis experiments 53. Also Zhijie G investigated the extracts of Couepia polyandra and Edgeworthia gardneri revealed the presence of stigmasterol along with other constituents and stigmasterol was found to inhibit the lyase activity of DNA polymerase β and also potentiate the inhibitory effect of the anti-cancer drug bleomycin in cultured A549 cells. These actions were a result of an inhibition of DNA repair synthesis 54.
Hypoglycemic activity and effect on thyroid: Chloroform extract of Parkia speciosa was orally administered to the alloxan- induced diabetic rats and it was found to produce a significant depression in blood glucose levels. Structure elucidation of the hypoglycaemic fractions showed the presence of stigmasterol along with β-sitosterol. When these constituents were tested individually they showed no activity which concluded that synergism between these two is necessary to produce the effect 55. Further, Panda S investigated that, stigmasterol isolated from the bark of Butea monosperma revealed that administration of stigmasterol to mice for 20 days reduced serum triiodothyronine (T3), thyroxin (T4), glucose concentration and the activity of hepatic glucose-6-phosphate with a significant increase in insulin indicating its thyroid inhibiting and hypoglycaemic property 56.
Antioxidant: Stigmasterol present in bark of Butea monosperma showed decrease in hepatic lipid peroxidation and increase in the activities of catalase, superoxide dismutase and glutathione thereby suggesting its antioxidant property 56.
Antimutagenic activity: Thorns of Gleditsia sinensis was investigated for their active constituents and their antimutagenic activity. One terpenoid and four steroids were isolated from the plant out of which stigmasterol was the most active antimutagen showing 51.2% and 64.2% reduction of the induction factor against the mutagen MNNG and NQO respectively, in the SOS chromo test 57.
Anti-inflammatory activity: Acetone extract of Sideritis foetens was found to contain sterol fractions composed of stigmasterol, β-sitosterol and campesterol. These fractions were evaluated for their anti-inflammatory activity and they were found to reduce carrageenan induced paw oedema and also inhibited ear oedema induced by 12-O- tetradecanoylphorbol acetate (TPA) after topical application 58. Also, stigmasterol isolated from Eryngium foetidum (Apiaceae) was evaluated by Garcia MD, focussing on auricular oedema induced by 12-O-tetradecanoylphorbol acetate (TPA), by single and multiple application of phlogistic agent and was found to reduce oedema. It also exerts a significant topical anti-inflammatory action 59.
CNS activities: The petroleum ether extract of aerial parts of Celesia coromandeliane on preparative TLC gave a fraction which upon IR study revealed that the compound has structural similarity with stigmasterol derivatives and this showed significant analgesic activity as it significantly reduced the number of writhes and stretches induced in mice by 1.2% acetic acid solution. Pretreatment with these fractions caused substantial protection against strychnine- and leptazol- induced convulsions 60. Likewise, leaf extract of Perilla frutescens showed sedative activity as a result of combined effect of stigmasterol and perillaldehyde. Other combinations of the components did not show the same results 61.
CONCLUSION: From the above information it is clear that stigmasterol and its derivatives are of utmost importance and is therefore imperative to further investigate these compounds. Out of numerous valuable constituents found, stigmasterol is one of the potential one and has been isolated from many plants till date and evaluated for many pharmacological and biological activities. It is jussive that more pharmacological studies should be conducted to evaluate the unexploited potential of this constituent.
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Navpreet Kaur, Jasmine Chaudhary*, Akash Jain and Lalit Kishore
M. M. College of Pharmacy, M.M. University, Mullana, Ambala, Haryana- 133207, India
09 May, 2011
29 June, 2011
17 August, 2011
01 September, 2011