The effect of Sutherlandia frutescens on steroidogenesis: confirming indigenous wisdom.
Sutherlandia frutescens (Cancer bush), a Southern African indigenous plant, is traditionally used to treat stress related maladies linked to the endocrine system. Extracts of the shrub were used to investigate the claimed stress-relieving properties of the shrub. Dysregulation of the stress response is associated with elevated glucocorticoid levels. A model of chronic intermittent immobilization stress was investigated in 40 adult male Wistar rats to determine the effect of Sutherlandia. Immobilization stress resulted in increased corticosterone levels in the control group while rats receiving Sutherlandia extract showed significantly decreased corticosterone levels (P < 0.005). Since the biosynthesis of glucocorticoids in the adrenals is catalyzed by the cytochrome P450-dependent enzymes, the influence of Sutherlandia extracts on adrenal steroidogenesis was determined in ovine adrenocortical microsomes and mitochondria, using spectral binding and enzyme conversion assays. Water extracts showed inhibition of substrate binding to cytochrome P450 21-hydroxylase (CYP21) by 38% and cytochrome P450 11beta-hydroxylase (CYP11B1) by 60%. The conversion of progesterone and pregnenolone was inhibited by 34% and 30%, respectively. Subsequent extractions with chloroform and methanol showed inhibition of substrate binding and conversion with hydrophobic compounds exhibiting a greater inhibitory effect on deoxycorticosterone binding to CYP11B1 (30%) and on progesterone binding to CYP21 (50%). The inhibition of binding of pregnenolone to CYP17 by the chloroform extract was 62%, with negligible inhibition by the methanol extract. The chloroform extract showed a greater inhibitory effect than the methanol extract on progesterone and pregnenolone metabolism (20%-50%).
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Department of Biochemistry, University of Stellenbosch, Stellenbosch, South Africa.
Smith
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Swart
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Swart
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D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D003345:Corticosterone / Q000097:blood*; D003900:Desoxycorticosterone / Q000037:antagonists & inhibitors / Q000378:metabolism; D007887:Fabaceae / Q000737:chemistry*; D007103:Immobilization; D007274:Injections, Intraperitoneal; D008297:Male; D016488:Medicine, African Traditional; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D011284:Pregnenolone / Q000037:antagonists & inhibitors; D011374:Progesterone / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D012756:Sheep; D013252:Steroid 11-beta-Hydroxylase / Q000378:metabolism; D013255:Steroid 21-Hydroxylase / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis*; D013312:Stress, Physiological / Q000097:blood* / Q000209:etiology
D010936:Plant Extracts; D013256:Steroids; D003900:Desoxycorticosterone; D011374:Progesterone; D011284:Pregnenolone; D013255:Steroid 21-Hydroxylase; D013252:Steroid 11-beta-Hydroxylase; D003345:Corticosterone