Effects of Ficus thonningii (Blume) [Morarceae] stem-bark ethanolic extract on blood glucose, cardiovascular and kidney functions of rats, and on kidney cell lines of the proximal (LLC-PK1) and distal tubules (MDBK).

ABSTRACT

Previous observations indicate that Ficus thonningii (Blume) [Moraceae] stem-bark extracts may be useful in the control of diabetes mellitus. Accordingly, we investigated in some experimental animal paradigms the effects of F. thonningii stem-bark ethanolic extract (FTE) on renal and cardiovascular functions as complications of diabetes. Oral glucose tolerance tests were conducted in separate groups of non-diabetic and STZ-treated diabetic rats given glucose load (0.86 g x kg(-1), p.o.) after 18-h fast, followed by various FTE doses (60, 120, and 240 mg x kg(-1)). Rats treated with deionized water (3 mL x kg(-1) p.o.), or metformin (500 mg x kg(-1) p.o.) acted as untreated and treated positive controls, respectively. Blood glucose was monitored at 15-min intervals for the first hour, and hourly thereafter for 3 h. Acute effects of FTE on kidney function and mean arterial blood pressure (MAP) were investigated in anaesthetized rats challenged with hypotonic saline after a 3.5-h equilibration for 4 h of 1 h control, 1.5 h treatment, and 1.5 h recovery periods. FTE was added to the infusate during the treatment period. Chronic effects of FTE were studied in individually caged rats treated daily with FTE (120 mg x kg(-1), p.o.) for five weeks. Cytotoxicity of FTE was assessed by dye-reduction colorimetric (MTT) assay on MDBK and LLCPK1 kidney cell lines exposed for 24 h, 48 h, and 72 h to graded concentrations of the extract. Myocardial contractile performance was evaluated on rat isolated atrial muscle strips. FTE, like metformin, decreased blood glucose levels in non-diabetic and STZ-diabetic rats. Both acute and chronic FTE treatments did not affect renal function. In vitro studies demonstrated that FTE increased MDBK cell metabolic activity by an average of 15% (72 h), and LLCPK1 mirrored the controls. Acute intravenous infusion of FTE reduced the MAP from 119 +/- 1 mmHg to 98 +/- 4 mmHg. The MAP also was reduced throughout the five-week experimental study period. FTE also produced concentration-dependent, negative inotropic and chronotropic effects on rat isolated, electrically driven left-, and spontaneously beating right-, atrial muscle preparations. Our experimental findings suggest that FTE possesses reno- and cardio-protective effects in diabetes mellitus.