The antianxiety effects of koumine and gelsemine, two main active components in the traditional Chinese herbal medicine Gelsemium: A comprehensive review

The genus Gelsemium belongs to the family Loganiaceae, one of the traditional Chinese herbs. Gelsemium is traditionally used to treat rheumatoid and neuropathic pain. Its root extracts were found to protect against anxiety, especially the alkaloids koumine and gelsemine. Indeed, koumine and gelsemine can act as positive agonists of the glycine receptor (GlyR), which reduces neuronal excitability through chloride influx and can also increase neuroactive steroid content by enhancing 3alpha-hydroxysteroid oxidoreductase (3α-HSOR) expression. The latter can activate the excitation-inhibitory response via the γ-aminobutyric acid type A receptor (GABA_AR), reduce the abnormal corticotropin-releasing hormone (CRH) increase in the hypothalamus, inhibit adrenocorticotropic hormone (ACTH) secretion, and effectively inhibit the abnormal ACTH and corticosterone increases in the circulation. In addition, koumine and gelsemine inhibited the expression of the NLR family pyrin domain containing 3 (NLRP3) inflammasome, inhibiting the release of inflammatory factors and regulating anxiety-related neural circuits. Gelsemine also inhibited the overexpression of brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB) in the hypothalamus to maintain the plasticity of brain neurons and protect neurogenesis to achieve anxiety regulation. In general, this article reviews the recent studies on Gelsemium in the anxiety field, discusses its possible antianxiety mechanism, and confirms the potential of Gelsemium as a therapeutic drug for anxiety-related diseases.