Safety Evaluation of Two Nigerian Polyherbal Formulations (Fidson Bitter® And Daily Living Bitter®) In Male Wistar Rats

Background: Herbal bitters are used for diverse diseases based on the manufacturers’ assertions. However, little is known about their toxicity profile.Objective: The safety profile of two commonly used herbal bitters in Nigeria (Fidson bitter® and Daily living bitter®)was evaluated in rats.Materials and Methods: Single oral dose, 2 g/kg, of each reconstituted bitter extract was administered to male and female rats in acute toxicity test. Animals were observed for 14 days for behavioral changes and mortality. In sub-acute oral toxicity experiment, 250 mg/kg and 500 mg/kg of each bitter was separately administered daily to different groups of male Wistar rats for 30 days. Safety profile of concurrent administration of these bitters was also assessed. Histopathological, hematological, and clinical chemistry indices were evaluated.Results: The LD50 was found to be >2 g/kg. Daily living bitter® (DLB) had no significant effect on any of the indices evaluated (P>0.05). However, Fidson bitter® caused significant reductions in white blood cells count (WBC) compared with the control. Concomitant administration of the bitters resulted in significant (P<0.05) weight gain (up to 33 %), reduction in WBC and congestion of the liver without corresponding increase in liver biomarkers.Conclusion: Daily living bitter® was safe in sub-acute administration while Fidson bitter®and combination of the two bitters reduced white blood cell count. Hence, caution should be exercised in using Fidson bitter® or combination of the two bitters in humans as findings suggest possibility of immune suppression.Keywords: Toxicity profile, Polyherbal, Herbal bitters, Hematology, Wistar rats

Effects of Coadministration of Extract of Carica papaya Linn (family Cariaceae) on Activity of Two Oral Hypoglycemic Agents

Purpose: To investigate the interacting effects of co-administration of Carica papaya leaf extract on the hypoglycemic activity of metformin and glimepiride in an animal model. Method: Experimental factorial design was used to evaluate the individual and interaction influence of three variables ie nature (N), dose administered (C) and duration of administration (D), in a 23(=8) employed at two levels - ‘’high’’ and ‘‘low’’ - on blood glucose of diabetic rats on administration of ethanolic leaf extract of Carica papaya and two hypoglycemic agents, metformin and glimepiride. Unpaired t-test was used to test for significant difference due to administration of the combination Results: Extract of Carica papaya at 5.0 mg/kg produced significant blood glucose reduction with no significant reduction at the higher dose of 10 mg/kg (p>0.05). Changing nature from "low" (Carica papaya extract) to "high" (glimepiride or metformin) did not significantly change hypoglycemic activity. Generally, the ranking of the interacting effects was ND>CD>>NC for glimepiride/extract, and CD>ND>NC for metformin/extract. Administration of higher dose of the extract led to significant (p<0.01) increase in onset of activity of glimepiride. The onset of activity of metformin was not affected, but a significant lowering (p<0.05) of blood glucose was observed at 24 hr with all combinations of extract and metformin. Conclusion: Leaf extract of Carica papaya significantly delays the onset of hypoglycaemic activity of glimepiride, and increases the hypoglycaemic effect of metformin with the variables interacting differently for each drug-extract combinations