AshwagandhavsCordyceps

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.

Cordycepin (3'-deoxyadenosine), the primary bioactive compound, increases ATP production by enhancing mitochondrial electron transport chain efficiency — it may act as an alternative substrate or modulator of Complex I and Complex III. Cordycepin activates AMPK (AMP-activated protein kinase) via increased AMP/ATP ratio or direct activation of the alpha subunit, promoting glucose uptake through GLUT4 translocation and fatty acid oxidation via CPT-1 and ACC inhibition. Cordyceps increases erythropoietin (EPO) production, likely through HIF-1alpha stabilization in hypoxic-sensitive tissues, improving oxygen-carrying capacity. Cordycepin has adenosine-like activity, modulating purinergic P1 (A1, A2A, A2B, A3) and P2 receptors. Anti-inflammatory effects occur through inhibition of NF-kB (reducing IKK degradation of IkB and nuclear translocation) and reduction of pro-inflammatory cytokines (IL-1beta, IL-6, TNF-alpha). Adenosine deaminase-resistant cordycepin may also affect RNA polyadenylation.