Srijayanta, Sairavee; (2000) Biological And Phytochemical Studies On Some Traditional Anti-diabetic Plants. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This current study aim s to investigate the effect o f selected medicinal plants on anti-diabetic activity, focusing on potential inhibitory effects on intestinal glucose absorption and a stim ulatory effect on insulin secretion from pancreatic Pcells using tw o different in vitro m odels, brush border m em brane vesicles (BBM V) and an insulin secreting cell line - RINmSF cells. Plants used in the studies were selected based on their reputations as anti-diabetic rem edies in some countries with varying degrees o f scientific evidence to support their traditional use. Investigation o f the effect o f the aqueous extracts o f the selected plants revealed four plants w hich were capable o f causing marked inhibition o f glucose uptake into BBM V. These plants w ere L ycium chinensis (Solanaceae), P iper longum (Piperaceae), P tero ca rp u s m arsupium (Legum inosae) and Salacia reticulata (C elastraceae). The results suggested that the inhibition observed in these cases was not associated w ith glucose in the extracts w hich could interfere w ith the assay, as the extracts appeared to contain negligible am ount o f glucose. There was a possibility that these plants contained active constituents that were capable of inhibiting a transport activity o f S G L T l, a transporter o f glucose across the brush border. This is the first study to report the effect o f these plants on this model. Bioassay-guided fractionation o f L. chinensis afforded the isolation o f a pure com pound w hich, by means o f N M R and M ass spectrom etry, was identified as sitosterol glucoside. Investigation o f the effect o f aqueous extracts o f the selected plants on RINm5F cells revealed two plants w hich were capable o f stim ulating insulin secretion. These plants were A n em a rrh en a asph o d elo id es (Liliaceae) and a mem ber o f the genus P a rv a tia (Lardizabalaceae). The effect o f these plants did not appear to be associated w ith cell m em brane dam age as judged by lack o f appreciable LDH leakage from the cells after exposure to the extracts. However, no further study was conducted on P a rv a tia spp., since the identity o f this plant was am biguous. Bioassay guided fractionation o f A. a sp hodeloides m ethanolic extract w hich was found to have the m ost potent activity resulted in the isolation o f 4 com pounds i.e. m angiferin, m angiferin glucoside, tim osaponin AIII and tim osaponin BI. O f these, m angiferin w as able to stim ulate the secretion o f insulin from both RINmSF cells and rat islets. The effect o f m angiferin was found to be potentiated by the presence o f nutrient, suggesting that the com pound may have potential advantages for use in the treatm ent o f NIDDM as it w ould cause greater insulin release following a meal than in basal conditions. It appeared that the stim ulation o f insulin release caused by m angiferin was associated neither to PK A nor PKC pathway in the secretory response. M angiferin glucoside was found to cause a significant secretion o f insulin from RINmSF cells but not in rat islets. U nlike m angiferin, the effect o f m angiferin glucoside did not appear to be potentiated by the presence o f nutrient. Tim osaponin AIII was found to be a very potent insulin secretagogue, the com pound as low as 1-8 pg/m l was found to cause a significant release o f insulin from RINmSF cells without dam aging cell membranes. In contrast to tim osaponin AIII, tim osaponin BI was found to have no effect on insulin secretion from RINmSF cells. Besides these four com pounds, two other com pounds were also isolated from non active fraction o f methanolic A. asphodeloides extract i.e. cis hinokiresinol and 4'-m ethyl-cw - hinokiresinol.

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