Harmaline attenuates pain and inflammation: role of IL-1β, oxidative stress, nitric oxide and cyclo-oxygenase.

Harmaline, a naturally occurring β-carboline alkaloid found in plants such as Peganum harmala and Banisteriopsis caapi, exhibits various pharmacological activities, including antioxidant and neuroprotective properties. Its free radical-scavenging ability contributes to cellular protection against oxidative stress. Based on these properties, the present study aimed to explore the antinociceptive and anti-inflammatory effects of harmaline using acetic acid-induced writhing and carrageenan-induced paw edema mice models. Mice were treated with acetic acid to induce writhing, and carrageenan was administered to induce paw edema. Following carrageenan administration, the animals were euthanized, and paw tissues were harvested for biochemical analysis. Harmaline significantly reduced the frequency of acetic acid-induced writhing and attenuated carrageenan-induced inflammation, as indicated by a decrease in paw thickness. Biochemical analysis revealed that harmaline (5 mg/kg) reduced lipid peroxidation and preserved GSH levels in paw tissues, highlighting its antioxidant effects. Furthermore, harmaline treatment lowered IL-1β levels and upregulated Nrf-2, indicating modulation of inflammatory and antioxidant signaling. Pre-treatment with substance P and L-arginine reversed harmaline's effects on writhing and paw edema, suggesting the involvement of cyclo-oxygenase and nitric oxide pathways. These pre-treatments also reversed the harmaline-induced reduction in TBARS and IL-1β levels, as well as elevation of GSH and Nrf-2 levels, further supporting the involvement of these pathways. Overall, this study demonstrates that harmaline effectively alleviates pain and inflammation through the inhibition of COX and nitric oxide pathways, alongside the activation of Nrf-2-antioxidant signaling. These findings support harmaline's potential as a therapeutic agent for pain and inflammation, warranting further research into its clinical applications.