Sutherlandia frutescens modulates adrenal hormone biosynthesis, acts as a selective glucocorticoid receptor agonist (SEGRA) and displays anti-mineralocorticoid properties.
BACKGROUND
Sutherlandia frutescens is a traditional African medicinal plant used in the treatment of stress and anxiety, while also exhibiting anti-inflammatory properties.


OBJECTIVE
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.


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.


CONCLUSIONS
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.
Department of Biochemistry, Stellenbosch University, Stellenbosch, South Africa.
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Sergeant
Department of Biochemistry, Stellenbosch University, Stellenbosch, South Africa.
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Africander
Department of Biochemistry, Stellenbosch University, Stellenbosch, South Africa.
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Swart
Department of Biochemistry, Stellenbosch University, Stellenbosch, South Africa. Electronic address: acswart@sun.ac.za.
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Swart
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D019556:COS Cells; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D007887:Fabaceae / Q000737:chemistry*; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D008901:Mineralocorticoids; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D011374:Progesterone / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000819:agonists*
D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D006727:Hormone Antagonists; D008901:Mineralocorticoids; D010936:Plant Extracts; D011965:Receptors, Glucocorticoid; D011374:Progesterone
Adrenal H295R cell model; Aldosterone; Anti-inflammatory; Cytochrome P450; Glucocorticoid receptor; SEGRA; Sutherlandia frutescens