Essential oil from Piper aduncum L. leaves exhibits analgesic and anti-inflammatory activity in mice

Piper aduncum L. is a medicinal plant whose essential oil is rich in bioactive constituents, particularly dilapiol, and has attracted interest because of its diverse pharmacological properties. However, its anti-inflammatory, antipyretic, and antinociceptive activities and the mechanisms potentially underlying these effects remain insufficiently characterized. Therefore, this study investigated the pharmacological effects of P. aduncum leaf essential oil (EO Pa ) and explored potential mechanisms involved in its antinociceptive activity. EO Pa was obtained by hydrodistillation and chemically characterized by GC–MS and GC–FID. Its pharmacological effects were evaluated in male Swiss mice using brewer’s yeast-induced pyrexia, carrageenan-induced paw edema, acetic acid-induced writhing, and the formalin test. Potential mechanisms of antinociceptive activity were investigated using naloxone, atropine, L-NAME, and glibenclamide as pharmacological antagonists/inhibitors. Chemical characterization identified dilapiol as the major constituent of EOPa (69.65 ± 2.12%). EOPa showed dose-dependent anti-inflammatory, antipyretic, and antinociceptive effects, with the most pronounced activity observed at 200 mg/kg. The essential oil reduced inflammatory edema, fever, and nociceptive responses in the experimental models. EOPa at 200 mg/kg reduced yeast-induced fever by up to 76.1% ( p < 0.01), carrageenan-induced paw edema by up to 26.48% ( p < 0.0001), and acetic acid-induced writhing by 65.90% ( p < 0.001). In the formalin test, EO Pa reduced nociceptive behavior by 39.89% during the neurogenic phase and by 70.67% during the inflammatory phase ( p < 0.0001). Pretreatment with atropine and glibenclamide markedly attenuated the antinociceptive effect of EO Pa , whereas naloxone and L-NAME did not significantly modify the response. These findings provide preclinical evidence that P. aduncum leaf essential oil possesses anti-inflammatory, antipyretic, and antinociceptive activities and suggest that the antinociceptive effect of EOPa involves activation of muscarinic receptors, consistent with a muscarinic agonist-like effect, and stimulation of ATP-sensitive potassium (K + ATP ) channels, consistent with a K + ATP -channel-stimulating effect. Further pharmacological, toxicological, and mechanistic studies are warranted to clarify the molecular basis, active constituents, and safety profile of these effects.