Antihyperglycemic Profile of Erinidine Isolated from Hunteria Umbellata Seed

Water decoction made from the seed of Hunteria umbellata is widely used in the traditional management of diabetes mellitus by Nigerian herbalists, particularly, in the southwest region of the country. Recently, a new bisindole alkaloid, erinidine, was isolated but its antihyperglycemic profile remains largely un-investigated scientifically. This forms the basis for the current study which is primarily designed at investigating the antihyperglycemic profile of erinidine and other fractions in both in vitro and in vivo models of diabetes mellitus. In the present study, erinidine was isolated and purified using the earlier described methods and its antihyperglycemic potentials tested in in vitro models such as dipeptidylpeptidase (IV), glycogen phosphorylase, HIT-T15 cell insulin secretion, glucose uptake activity, aldose reductase assays and α-glucosidase inhibition assay testings. In addition, 50 mg/kg of erinidine and that of other fractions were evaluated in in vivo models of normal and chemically-induced hyperglycemic rats. Results showed that erinidine was a light yellow, amorphous solid with UV (CHCl₃) λ_max 256 nm, HRESIMS m/z 382.1881 [(M+H)⁺] (calculated for C₂₂H₂₆N₄O₂, 382.1876) and melting point of 230 °C. The in vitro study showed the antihyperglycemic action of erinidine to be weakly mediated via α-glucosidase inhibition mechanism as the results for other in vitro tests such as dipeptidylpeptidase (IV), glycogen phosphorylase, HIT-T15 cell insulin secretion, glucose uptake activity and aldose reductase assays were all negative. However, the in vivo results showed 50 mg/kg erinidine given per os to normal and alloxan-induced hyperglycemic rats to significantly (p<0.05, p<0.001) attenuate an increase in their post-absorptive blood glucose concentrations after 3 g/kg glucose loading in the rats, suggesting its antihyperglycemic mechanism to be via α-glucosidase inhibition. This result, although, further corroborated the in vitro findings but also suggests that erinidine needs to be biotransformed in vivo for its inhibitory activity on intestinal glucose absorption to become evident. Thus, the present study suggests erinidine to be the possible antihyperglycemic agent in Hunteria umbellata seed extract mediating its antihyperglycemic action via intestinal glucose uptake inhibition.     

Hypoglycaemic and hypotensive effects of Ficus exasperata vahl. (Moraceae) leaf aqueous extract in rats

The hypotensive and hypoglycaemic effects of Ficus exasperata (Vahl) (family: Moraceae) leaf aqueous extract (FEE) were investigated in experimental rat models. In this study, spontaneously-hypertensive rats (SHR) (type 1 diabetes), obese Zucker (type 2 diabetes) and Wistar rats were used. Three (A, B and C) groups of rats, each group consisting of 10 rats, were used. Group A Wistar rats received distilled water in quantities equivalent to the volume of streptozotocin (STZ) and FEE administered intraperitoneally to treated rats. Diabetes mellitus was induced in the SHR group B rats by multiple low-dose (MLD) intraperitoneal injections of STZ (40 mg/kg body weight) to induce type 1 diabetes. The animals in group C were the obese Zucker rats with non-insulin-independent diabetes mellitus (NDDM) (type 2 diabetes) on genetic basis. F. exasperata leaf aqueous extract (FEE, 100 mg/kg/day p.o.) was administered orally by orogastric intubation to fasted Groups B and C rats. In groups B and C rats, administration of FEE commenced 4 weeks post STZ injection, and continued for the next 4 consecutive weeks. Group A rats gave normal biochemical and morphological findings. Group B rats exhibited pronounced polyuria, hypoinsulinaemia, hyperlipidaemia and hyperglycaemia. These findings were also observed in group C rats, except that there was hyperinsilinaemia. Histopathological study of the aortic blood vessels showed extensive collagen fiber formation as well as perivascular fibrosis in both groups B and C rats. Four weeks of oral administration of F. exasperata leaf aqueous extract to diabetic groups of rats decreased blood glucose, blood pressure and lipid profiles. Administration of FEE (100 mg/kg p.o.) also restored the microanatomy of the blood vessels to almost normal levels. The findings of this study suggest that F. exasperata leaf aqueous extract possesses hypoglycaemic, hypotensive and hypolipidaemic properties. These findings lend biomedical and pharmacological support to the folkloric, ethnomedical uses of the plant in the management and/or control of diabetes and hypertension among the Yoruba-speaking people of Western Nigeria.