AshwagandhavsHoly Basil (Tulsi)

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.

Holy basil's adaptogenic effects come from multiple compounds: eugenol (anti-inflammatory via COX-2 and 5-LOX inhibition, TRPV1 modulation), ursolic acid (cortisol modulation via 11beta-HSD inhibition and glucocorticoid receptor modulation), rosmarinic acid (antioxidant via Nrf2/ARE pathway, anti-allergic via mast cell stabilization), and ocimumosides A and B (anti-stress via CRH and corticosterone reduction). It modulates the HPA axis, normalizing cortisol and corticosterone levels through hypothalamic and adrenal effects. Ursolic acid inhibits acetylcholinesterase (AChE), mildly increasing synaptic acetylcholine. Eugenol provides direct anxiolytic effects through GABA-A receptor positive allosteric modulation (possibly at the beta2/3 subunit interface) and 5-HT1A partial agonism. Ocimumosides may reduce ACTH release from the pituitary.