Abstract
Piper guineense, Gongronema latifolium and Cymbopogon citratus (PGC) serve as an effective polyherbal antisickling extract used in the management of sickle cell disorder. This present study assessed the toxicity effect of the ethanol leaf extract of PGC in rats. The acute oral toxicity test of the polyherbal was evaluated in albino rats using a single-dose based on behavioral changes and mortality. Sub-acute toxicological evaluation of PGC was examined using biochemical, hematological and histopathological methods. Biochemical analysis was carried out using liver markers enzymes, kidney markers enzymes, and lipid profiles. The hematological measurement includes white blood cell counts (WBC), Lymphocytes (LYM), monocytes (MON), granulocytes (GRAN), Red blood cell count (RBC). The organs (liver, kidney, and heart) were collected and prepared using standard protocols with hematoxylin and eosin for histopathological evaluation. The acute toxicity study of ethanol leaf extract of PGC up to the limit dose of 2000 mg/kg body weight of the animals used did not produce any signs and symptoms of toxic effects or mortality after 48 hrs. of oral administration. There were no significant differences (p < 0.001) in the observed values between the control and the treated groups for all the biochemical and hematological parameters analyzed. Histopathological evaluation of the organs demonstrated mild degeneration in the kidney and liver while the heart revealed no pathological changes in the treated group of rats. The result of acute toxicity indicates that the combined antisickling polyherbal PGC extract appeared to be safe and non- toxic. Our findings for the 28 days daily oral administration of PGC extract was dose dependent and well tolerated by the animals. Although, slight changes were observed in some biochemical parameters and histology of the kidney and liver at high doses when compared with control rats. Therefore, the consumption of the antisickling polyherbal PGC extract orally should be used encouraged at lower doses and high doses should be avoided for the management of sickle cell disorder until subjected to further cytotoxicity evaluation. 
 Keywords: Polyherbal combination, acute toxicity, subacute toxicity, biochemical parameter, hematological parameter, histopathological parameters.
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