Assessment of anti-diabetic effect of Vietnamese herbal drugs

University dissertation from Stockholm : Karolinska Institutet, Department of Molecular Medicine

Abstract: he prevalence of type 2 diabetes mellitus is increasing in Vietnam as well as in other developing countries (China, Indian subcontinent, and Africa). Searching for hypoglycemic agents with origin from domestic herbals was considered as a useful way to find novel therapy of the disease. After treatment i.p. or orally of normal mice with extract of Anemarrhena asphodeloides (A.a.), Angiopteris evecta (A.e.) and Gynostemma pentaphyllum (G.p.), blood glucose levels of the mice were decreased. All of those 3 extracts also suppressed the rise in blood glucose in normal mice during a glucose tolerance test. At both 3.3 and 16.7 mM glucose, 2, 4 and 8 mg/ml Anemarrhena asphodeloides (A.a. or TH2) increased the insulin release of Wistar (W) and Goto-Kakizaki (GK) rat islets. In perifusions of islets, A.a. also increased insulin secretion that returned to basal levels when A.a. was omitted from the perifusate. Thus, ethanol extract of the roots of A.a. contains a substance, TH2, that stimulates insulin secretion from islets of normal W and GK rats. The mechanism behind TH2-stimulated insulin secretion involves an effect on the exocytotic machinery of the B-cell, mediated via pertussis toxin-sensitive Ge-proteins. G.p. extract had a hypoglycemic effect in rats and mice. We have isolated the active compound, phanoside, a gypenoside with molecular mass of 914.5 Da. When given orally to rats, phanoside (40 and 80 mg/kg) improved glucose tolerance and enhanced plasma insulin levels. Phanoside stimulated insulin release at 3.3 and 16.7 mM glucose from isolated rat pancreatic islets of both W and GK rats. Interestingly, B-cell sensitivity to phanoside is higher at 16.7 mM than at 3.3 mM glucose, since significant insulin responses were observed with phanoside between 31.25 and 125 ìM only at the high glucose levels. When W rat islets were incubated at 3.3 mM glucose with 150 ìM phanoside and 0.25 mM diazoxide to keep K-ATP channels open, insulin secretion was similar to that in islets incubated in 150 ìM phanoside alone. At 16.7 mM glucose, phanoside-stimulated insulin secretion was reduced in the presence of 0.25 mM diazoxide. In W islets depolarized by 50 mM KCl and with diazoxide, phanoside stimulated insulin release 2-fold at 3.3 mM glucose but did not further increase the release at 16.7 mM glucose. When using nimodipine to block L-type Ca2+ channels in B-cells, phanoside-induced insulin secretion was unaffected at 3.3 mM glucose but decreased at 16.7 mM glucose. In perifusion of islets, phanoside (75 and 150 ìM) dose-dependently increased insulin secretion that returned to basal levels when phanoside was omitted. Thus, the effect of phanoside seems to be exerted distal to K-ATP channels and L-type Ca2+ channels that is on the exocytotic machinery of the B-cells. In conclusion, from 8 Vietnamese herbal drugs, we have found 3 extracts which decreased blood glucose of the mice. Two of them (A.a and G.p. extract) stimulated insulin secretion from rat islets. Ethanol extract of A.a. (TH2) stimulated insulin secretion by an effect on the exocytotic machinery of the B cell mediated via pertussis toxin sensitive Ge-protein. From G.p. we islolated a novel substance, phanoside, that directly stimulates the exocytosis of insulin.

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