Gooderoside A from Anoectochilus elatus attenuates acute and chronic pains by inhibiting NO/cGMP and IRAK4/IRAK1/TAK1 signaling pathways

Anoectochilus elatus Lindl. was traditionally used for pain treatment and Gooderoside A (GA) was regarded as its principal constituent. To investigate whether GA can be responsible for the antinociceptive activity of A. elatus and explore its underlying mechanism. Acetic acid-induced abdominal writhing and tail flick tests were employed to evaluate the antinociceptive activity of ethanolic extract of A. elatus (EEA) and GA. Formalin test was used to ascertain the antinociceptive pattern of GA. Entobarbital sodium induced sleep test was adopted to exclude its hypnotic effect, while open-field test was performed to rule out its motor impairment effect. Chronic constriction injury (CCI)-induced neuropathic pain in rats was developed to evaluate its efficacy on neuropathic pain, and BV-2 cells were used to explore the underlying mechanism. EEA and GA, significantly inhibited chemical and thermal nociception. GA suppressed nociception in formalin test in both phase I and II, and quinidine totally abolished its antinociceptive effect, whereas methylene blue and L-NAME partially reversed its efficacy. GA located inner and slightly blocked sodium channel current, and did not show any hypnotic effect or motor impairment effect. Crucially, GA markedly attenuated chronic neuropathic pain in rats, inhibited the phosphorylation of IRAK4, IRAK1 and TAK1, and suppressed MAPKs pathway in BV-2 cells. GA relieved acute and chronic pains in vivo. The mechanism of action involves the blocking of NO/cGMP and IRAK4/IRAK1/TAK1 pathways. These results suggested GA may be a promising candidate for antinociceptive drug development.