Apigenin ‘s Dual Action on Pain and Inflammation: Mechanistic Insights Through NO, COX, and Oxidative Stress Pathways

Abstract:

Apigenin, a naturally occurring flavonoid known for its antioxidant and diverse pharmacological properties, was investigated for its potential analgesic and anti-inflammatory effects. The analgesic activity was evaluated using the acetic acid–induced writhing model, whereas anti-inflammatory efficacy was assessed through carrageenan-induced paw edema in Swiss albino mice. Oral administration of apigenin at doses of 25 and 50 mg/kg produced a significant, dose-dependent reduction in writhing responses. Furthermore, the higher dose markedly suppressed carrageenan-induced paw edema, demonstrating notable anti-inflammatory activity.Biochemical analyses revealed that apigenin significantly reduced interleukin-1β (IL-1β) levels while restoring the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), suggesting modulation of inflammatory mediators and oxidative stress–responsive signaling pathways. However, only modest alterations were observed in glutathione (GSH) levels and lipid peroxidation markers. Pharmacological modulation using substance P and L-arginine attenuated the protective effects of apigenin, indicating the possible involvement of nitric oxide and cyclooxygenase-associated signaling pathways in its mechanism of action, the findings demonstrate that apigenin exhibits significant analgesic and anti-inflammatory properties through the regulation of inflammatory cytokines and redox-sensitive molecular pathways, highlighting its therapeutic potential as a natural bioactive compound for the management of pain and inflammatory disorders.