Department of Biochemistry, Stellenbosch University, Stellenbosch, South Africa.
Department of Biochemistry, Stellenbosch University, Stellenbosch, South Africa.
J Ethnopharmacol. 2017 Apr 18;202:290-301. doi: 10.1016/j.jep.2017.03.019. Epub 2017 Mar 18.
Sutherlandia frutescens is a traditional African medicinal plant used in the treatment of stress and anxiety, while also exhibiting anti-inflammatory properties.
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.
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.
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.
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.
南非钩麻是一种传统的非洲药用植物，用于治疗压力和焦虑，同时也具有抗炎特性。
本研究旨在通过甾体激素受体相互作用，将南非钩麻的抗应激和抗炎特性与其对糖皮质激素生物合成和炎症反应的影响联系起来。
在 COS-1 细胞中测定南非钩麻提取物和 sutherlandioside B（SUB），10 和 30µM 对关键甾体生成酶的影响。还在肾上腺 H295R 细胞模型中测定了对基础和刺激激素水平的影响。随后研究了提取物和 SUB 对糖皮质激素受体（GR）和盐皮质激素受体（MR）的转录激活和转录抑制作用的激动剂活性。
提取物对 CYP17A1 和 CYP21A2 转化孕酮的抑制作用显著。SUB 抑制 CYP17A1 和 3β-HSD2，但不影响 CYP21A2。在 H295R 细胞中，SUB 显著降低皮质醇和雄激素前体。提取物降低总类固醇生成（基础和刺激），同时皮质醇及其前体脱氧皮质醇以及盐皮质激素代谢物在 forskolin 刺激条件下显著减少。南非钩麻提取物和 SUB 抑制 NF-κB 驱动的基因表达，而不激活 GRE 驱动的基因表达，同时既不激活 MR 介导的基因转录，又通过 MR 拮抗醛固酮的作用。
数据提供了证据，将南非钩麻的抗应激、抗炎和抗高血压特性与抑制甾体生成酶和调节肾上腺激素生物合成联系起来。表明南非钩麻和 SUB 表现出分离的糖皮质激素特性的发现，强调了它们在治疗炎症和高血压方面的潜在治疗应用。
