INHIBITION OF CYTOCHROME-P-450(11-BETA) BY SOME NATURALLY-OCCURRING ACETOPHENONES AND PLANT-EXTRACTS FROM THE SHRUB SALSOLA-TUBERCULATIFORMIS

Ingestion of the Namibian shrub Salsola tuberculatiformis Botsch. by v irgin female rats extends the dioestrus period of their oestrous cycle s. 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 co uld be obtained which indicated that the plant contains a number of ac tive compounds. The most active of these are highly unstable compounds which could not be isolated in pure form. However, two stable but les s active compounds were identified as 4-hydroxyacetophenone and 4-hydr oxy-3-methoxyacetophenone. This study investigated the influence of th ese acetophenones, their glucosides, and that of ethanol extracts of S . tuberculatiformis on adrenal steroidogenesis. Acetovanillon, a struc turally 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 11beta-hydroxylase, the terminal enzyme in glucocorticoid biosynthesis. This interaction with the cytochrome P -450(11beta)-dependent hydroxylase, as well as the inhibition of the c onversion of deoxycorticosterone to corticosterone, was used to develo p two sensitive and reliable assays for the rapid identification of sm all amounts of active compounds from S. tuberculatiformis.