Evidence of mechanism of action of anti-inflammatory/antinociceptive activities of acacetin

Background Acacetin is a bioflavonoid with pharmacological properties such as antinociceptive/anti‐inflammatory activities. However, scientific evidence of its spectrum activity and mechanisms of action is unknown. Methods Acacetin administered via i.p. was assessed using several nociceptive experimental models such as the writhing test, the formalin test and carrageenan paw oedema in the thermal plantar tests (Hargreaves method) in mice, as well as the pain‐induced functional impairment model in rat (PIFIR model). Results Acacetin produced a significant and dose‐dependent inhibition of the writhes with an ED50 = 20 mg/kg. Furthermore, acacetin inhibited licking and shaking associated with nociceptive behaviour mainly in the inflammatory phase of the formalin test. No significant differences were observed in the plantar test in mice, but a minor response was obtained in the PIFIR model. Animals receiving pre‐treatment of WAY100635 (0.1 mg/kg, s.c.), flumazenil (3 mg/kg, i.p.) or naloxone (1 mg/kg, i.p.) partially reduced the antinociceptive response of acacetin in the writhing test. Presence of the inhibitors in the NO‐cGMP‐K+ channel pathway did not modify the antinociceptive effect of acacetin in the writhing or the formalin test. Conclusions Our data showed that systemic administration of acacetin decreased visceral and inflammatory nociception and prevented the formalin‐induced oedema. In the mechanism of the acacetin antinociceptive effect, 5‐HT1A, GABA/BDZs and opioid receptors but not the NO‐cGMP‐K+ channel pathway seem to be involved. The data presented prove acacetin to be potentially useful in the therapy of pain‐related diseases.