Inhibition of Cytochrome P-450_11β by Some Naturally Occurring Acetophenones and Plant Extracts from the Shrub Salsola tuberculatiformis

Abstract

Ingestion of the Namibian shrub Salsola tuberculatiformis Botsch. by virgin female rats extends the dioestrus period of their oestrous cycles. Methanol extracts of the plant also inhibit adrenal steroidogenesis in the rat. With the aid of a bioassay, in which vaginal smears were used to follow the oestrous cycles of virgin rats, active fractions could be obtained which indicated that the plant contains a number of active compounds. The most active of these are highly unstable compounds which could not be isolated in pure form. However, two stable but less active compounds were identified as 4-hydroxyacetophenone and 4-hydroxy-3-methoxyacetophenone. This study investigated the influence of these acetophenones, their glucosides, and that of ethanol extracts of S. tuberculatiformis on adrenal steroidogenesis. Acetovanillon, a structurally related natural product also known as compound Z, was included in this study. Results show that the shrub contains active substances which interfere with adrenal 11β-hydroxylase, the terminal enzyme in glucocorticoid biosynthesis. This interaction with the cytochrome P-450_11β-dependent hydroxylase, as well as the inhibition of the conversion of deoxycorticosterone to corticosterone, was used to develop two sensitive and reliable assays for the rapid identification of small amounts of active compounds from S. tuberdulatiforinis.

Key words

Salsola tuberculatiformis - acetophenones - adrenal steroidogenesis - acetovanillon - compound Z - cytochrome P-450_11β-dependent hydroxylase - adrenal 11β-hydroxylase - glucocorticoid biosynthesis