From tradition to evidence: exploring the neurochemical basis of medicinal plants in anxiety therapy

Anxiety disorders are associated with dysfunction in key neurotransmitter systems like, GABAergic, serotonergic, dopaminergic, noradrenergic, and endocannabinoid, alongside oxidative stress, neuroinflammation, and hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. Conventional pharmacotherapies offer symptomatic relief but often cause adverse effects and dependency. This review explores medicinal plants as alternative anxiolytic agents due to their multi-targeted mechanisms of action. The review analyzes medicinal plants traditionally used for anxiety relief, focusing on their bioactive compounds, including flavonoids, alkaloids, saponins, terpenoids, and polyphenols. Mechanisms of action evaluated include GABA-A receptor activation, serotonergic modulation, neuroendocrine regulation, and antioxidant activity. Bioactive compounds from medicinal plants demonstrate anxiolytic effects through modulation of neurotransmitters, reduction of cortisol levels, and regulation of neuropeptides such as brain-derived neurotrophic factor (BDNF) and neuropeptide Y (NPY). Additionally, several phytochemicals enhance endocannabinoid signaling, supporting their role in anxiety management. Medicinal plants offer promising potential as alternative treatments for anxiety disorders by targeting multiple neurochemical and neuroendocrine pathways. However, challenges such as standardization, pharmacokinetic variability, and lack of clinical validation must be addressed. Future research should prioritize optimized formulations and large-scale clinical trials to ensure efficacy and safety.