Atractylodin Produces Antinociceptive Effect through a Long-Lasting TRPA1 Channel Activation.

Hirosato Kanda, Yanjing Yang, Shaoqi Duan, Yoko Kogure, Shenglan Wang, Emiko Iwaoka, Miku Ishikawa, Saki Takeda, Hidemi Sonoda, Kyoka Mizuta, Shunji Aoki, Satoshi Yamamoto, Koichi Noguchi, Yi Dai

International journal of molecular sciences 2021 Mar 31

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Atractylodin (ATR) is a bioactive component found in dried rhizomes of Atractylodes lancea (AL) De Candolle. Although AL has accumulated empirical evidence for the treatment of pain, the molecular mechanism underlying the anti-pain effect of ATR remains unclear. In this study, we found that ATR increases transient receptor potential ankyrin-1 (TRPA1) single-channel activity in hTRPA1 expressing HEK293 cells. A bath application of ATR produced a long-lasting calcium response, and the response was completely diminished in the dorsal root ganglion neurons of TRPA1 knockout mice. Intraplantar injection of ATR evoked moderate and prolonged nociceptive behavior compared to the injection of allyl isothiocyanate (AITC). Systemic application of ATR inhibited AITC-induced nociceptive responses in a dose-dependent manner. Co-application of ATR and QX-314 increased the noxious heat threshold compared with AITC in vivo. Collectively, we concluded that ATR is a unique agonist of TRPA1 channels, which produces long-lasting channel activation. Our results indicated ATR-mediated anti-nociceptive effect through the desensitization of TRPA1-expressing nociceptors.

Citation

Hirosato Kanda, Yanjing Yang, Shaoqi Duan, Yoko Kogure, Shenglan Wang, Emiko Iwaoka, Miku Ishikawa, Saki Takeda, Hidemi Sonoda, Kyoka Mizuta, Shunji Aoki, Satoshi Yamamoto, Koichi Noguchi, Yi Dai. Atractylodin Produces Antinociceptive Effect through a Long-Lasting TRPA1 Channel Activation. International journal of molecular sciences. 2021 Mar 31;22(7)