Sub-acute toxicity of ethanol extract of Motandra paniculata (Poir) I.M. Turner (Apocynaceae) leaves in rats and antiproliferative activity of its bioactive compounds

Motandra paniculata (Poir.) I.M. Turner (Apocynaceae) is used traditionally in Africa and Nigeria to manage abscesses and abnormal growths. However, the bioactive constituents responsible and its toxicity profile are unknown. The aim was to isolate and characterise bioactive chemical compounds from M. paniculata dried leaves, assess its antiproliferative activity on ovarian cancer and skin melanoma cell lines as well as determine the sub-acute toxicity profile of crude ethanol leaf extract (EEMP) of the plant. Chromatographic and spectroscopic techniques were employed to isolate and characterise compounds from the ethyl acetate fraction of the M. paniculata (MPEA). The antiproliferative activity (IC₅₀) of the isolated compounds was evaluated on ovarian cancer (OVCAR-3) and melanoma (MDA-MB-435) cells using proliferation assays, as well as a cytotoxicity assay on Vero cells. Lethality of EEMP on brine shrimp nauplii was carried out. Sub-acute toxicity profile of EEMP (50, 100, 200 and 400 mg/kg) in Sprague-Dawley rats was investigated. Biochemical, haematological, histopathological and antioxidant parameters were obtained from blood and tissue samples of the animals. Five megastigmane-type terpenes (1–5) and a phenolpropane (6) were isolated from the plant for the first time. Compounds 1 - 4 displayed modest antiproliferative activity on OVCAR-3 and MDA-MB-435. Toxicity resulted in vascular congestion in kidney and brain rat tissues on oral administration of high doses of EEMP. EEMP displayed dose-dependent short-term toxicity in rats while compounds isolated from MPEA exhibited antiproliferative activity against human cancer cells.