THE HEPATOPROTECTIVE CYTOCHROME-P-450 ENZYME-INHIBITOR ISOLATED FROM THE NIGERIAN MEDICINAL PLANT COCHLOSPERMUM-PLANCHONII IS A ZINC SALT

Aqueous extracts of Cochlospermum planchonii Hook.f. (Cochlospermaceae ) rhizomes are used by native medical practitioners in northern Nigeri a to treat jaundice, An extract prepared by a laboratory adaptation of their method was hepatoprotective in carbon tetrachloride-treated rat s (CCl4), and it inhibited cytochrome P-450 enzymes, which constitutes a plausible hepatoprotective mechanism, A crystalline inhibitor (0.3% of dry weight of rhizomes) was isolated using inhibition of two rat c ytochrome P-450 enzymes, aminopyrine-N-demethylase and aniline hydroxy lase, as bioassays to guide fractionation by solvent partitioning, pol yamide column chromatography, preparative thin layer chromatography an d fractional crystallization. The inhibitor was identified as zinc for mate. by inductively coupled plasma atomic emission spectroscopy, nucl ear magnetic resonance spectroscopy and comparison with synthetic mate rial by powder X-ray diffraction crystallography, Synthetic and plant- derived zinc formate were equally effective as inhibitors of cytochrom e P-450 enzymes and as hepatoprotective agents in carbon tetrachloride -treated rats. Cochlospermum planchonii rhizomes contain unusually hig h levels of manganese and zinc, although much higher levels have been observed in plants considered to be hyperaccumulators of these metals.