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Sutherlandia Frutescens Modulates Adrenal Hormone Biosynthesis, Acts as a Selective Glucocorticoid Receptor Agonist (SEGRA) and Displays Anti-Mineralocorticoid Properties

Sutherlandia Frutescens Modulates Adrenal Hormone Biosynthesis, Acts as a Selective Glucocorticoid Receptor Agonist (SEGRA) and Displays Anti-Mineralocorticoid Properties

C A Sergeant, D Africander, P Swart, A C Swart

J Ethnopharmacol. 2017 Apr 18;202:290-301.

PMID: 28323049

Abstract:

Ethnopharmacological relevance:
Sutherlandia frutescens is a traditional African medicinal plant used in the treatment of stress and anxiety, while also exhibiting anti-inflammatory properties.
Aim of study:
The study aimed at linking anti-stress and anti-inflammatory properties of S. frutescens to its influence on glucocorticoid biosynthesis and the inflammatory response via steroid receptor interaction.
Materials and methods:
The influence of S. frutescens extracts and sutherlandioside B (SUB),10 and 30µM, on key steroidogenic enzymes was assayed in COS-1 cells. Effects were also assayed on basal and stimulated hormone levels in the adrenal H295R cell model. Agonist activity for transactivation and transrepression of the extract and SUB with the glucocorticoid- (GR) and mineralocorticoid receptor (MR) was subsequently investigated.
Results:
Inhibitory effects of the extract towards progesterone conversion by CYP17A1 and CYP21A2 were significant. SUB inhibited CYP17A1 and 3β-HSD2, while not affecting CYP21A2. In H295R cells, SUB decreased cortisol and androgen precursors significantly. The extract decreased total steroid production (basal and stimulated) with cortisol and its precursor, deoxycortisol, together with mineralocorticoid metabolites significantly decreased under forskolin stimulated conditions. S. frutescens extracts and SUB repressed NF-κB-driven gene expression without activating GRE-driven gene expression and while neither activated MR mediated gene transcription, both antagonized the effects of aldosterone via the MR.
Conclusion:
Data provide evidence linking anti-stress, anti-inflammatory and anti-hypertensive properties of S. frutescens to inhibition of steroidogenic enzymes and modulation of adrenal hormone biosynthesis. Findings suggesting S. frutescens and SUB exhibit dissociated glucocorticoid characteristics underline potential therapeutic applications in the treatment of inflammation and hypertension.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
CS3102703	Sutherlandioside B			Price

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