Sutherlandia frutescens is widely used in indigenous medicine for the treatment of stress- and anxiety-related disorders, and although anecdotal evidence has been scientifically confirmed, relatively little data are available on its potential mechanisms of action. We manipulated a rodent model of acute psychological stress by acutely administering a low dose (4 mg/kg body mass) of S. frutescens extract 30 min prior to stress exposure (1 h restraint), to elucidate both its central and peripheral mechanisms of action in the context of acute stress. After 1 h of exposure to stress, acute restraint resulted in a significant increase in plasma corticosterone levels (56 ± 33 versus 499 ± 50 ng/ml; P < 0.0001) and anterior pituitary adrenocorticotropic hormone (ACTH) levels (0.066 ± 0.017 versus 0.202 ± 0.033% fluorescent area; P = 0.07), while decreasing hippocampal glucocorticoid receptor (GR) and gamma-aminobutyric acid (GABA)(A)α1 receptor levels (both P < 0.05). While the low dose of S. frutescens administered did not seem to have an effect on the down-stream stress response, it abolished the stress-induced down-regulation of GR, in a manner independent of GABA(A)α1 receptor. Results suggest a non-sedative effect of low-dose S. frutescens and points to central mechanisms of action that is in support of the anecdotal claims for its effectiveness as complimentary treatment in chronic stress-associated diseases.
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