Anti-nociceptive effect and mechanism of madecassic acid

To date, the investigation of the functional composition of Centella asiatica (L.) Urban has been mainly focused on the triterpenoid saponins, with little research on the other compositions. The acetic acid-induced writhing, Eddy's hot plate and formalin tests were employed to investigate the anti-nociceptive effects of madecassic acid (MA). The experiment was divided into normal control group, acetylsalicylic acid (ASA) group, and the MA groups of low (10 mg/kg), medium (20 mg/kg) and high (40 mg/kg) dosage. Meanwhile, the anti-nociceptive effect of MA on the acetic acid and formalin-induced nociceptive models in the absence and presence of NAL (naloxone hydrochloride) was evaluated. To have an insight into the anti-nociceptive mechanisms of MA, the capsaicin- and glutamate-induced paw licking tests were also employed to evaluate the involvement of the vanilloid and glutamatergic systems, respectively. Results showed that MA exhibited good anti-nociceptive activity in the acetic acid-induced writhing test and the second phase of formalin test; the anti-nociceptive effect of MA in both the acetic acid and formalin-induced nociception was not effectively removed by NAL; MA (20 mg/kg and 40 mg/kg) effectively reduced the duration of biting/licking the capsaicin-injected paw with inhibition rates of 29.5% and 64.4%, respectively; MA (20 mg/kg and 40 mg/kg) distinctly shortened the time spent in biting/licking the glutamate-injected paw by 30.9% and 56.1%, respectively. In summary, MA induces significant peripheral anti-nociceptive effect, and the anti-nociceptive activities probably involve the modulation of glutamatergic systems and vanilloid systems (TRPV1) instead of the opioidergic system.