AshwagandhavsEmoxypine (Mexidol)

Ashwagandha's withanolide compounds (withaferin A, withanolide A, withanone) modulate the hypothalamic-pituitary-adrenal (HPA) axis, reducing corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) signaling, thereby lowering cortisol production by 25-30% in stressed individuals. It acts as a GABA-A receptor positive allosteric modulator at the benzodiazepine site, producing anxiolytic effects without sedation. Ashwagandha inhibits acetylcholinesterase (AChE), raising acetylcholine levels in the hippocampus and cortex. The withanolides have anti-inflammatory properties via inhibition of NF-κB and COX-2, and antioxidant effects that reduce neuroinflammation and oxidative stress. It may support neurogenesis through upregulation of BDNF and its receptor TrkB, and modulation of the PI3K/Akt pathway.

Emoxypine (2-ethyl-6-methyl-3-hydroxypyridine succinate) has a 3-hydroxypyridine structure similar to vitamin B6 (pyridoxine). It is one of the most potent inhibitors of lipid peroxidation in brain tissue — it scavenges hydroxyl radicals and peroxyl radicals, inhibits Fe2+-induced lipid peroxidation, and may chelate transition metals. It modulates the GABA-benzodiazepine receptor complex (GABA-A), enhancing GABAergic transmission through positive allosteric modulation — possibly at a site distinct from the classical benzodiazepine binding site, explaining the lack of sedation and tolerance. It improves mitochondrial function (Complex I protection, membrane stabilization), stabilizes cell membranes (reducing fluidity changes during oxidative stress), and enhances cerebral microcirculation (possibly via nitric oxide or prostaglandin modulation). The anxiolytic mechanism may involve partial agonism or different subunit selectivity.