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Iridoids isolated from Viticis Fructus inhibit paclitaxel-induced mechanical allodynia in mice

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Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) manifests as mechanical allodynia and hyperalgesia, and is one of the main adverse effects of chemotherapeutic agents. Currently available therapeutic drugs are not sufficiently effective for the management of this adverse effect in the clinic. Therefore, the development of novel therapeutic agents for treating CIPN is necessary. Our previous study suggested the potential of aucubin and pedicularis-lactone (1) as active compounds responsible for the anti-allodynic property of Plantaginis Semen. However, the activity of purified 1 has not been evaluated due to its low content in Plantaginis Semen. In the present study, 1 was isolated from Viticis Fructus, as well as viteoid I (2) and viteoid II (3) during the process of isolation. The purities of isolated 1, 2, and 3 were determined as 67.15%, 92.12%, and 86.72%, respectively, by quantitative 1H-NMR, using DSS-d6 as an internal standard. Repeated daily oral administration of these three iridoids at a dose of 15 mg/kg significantly inhibited the PTX-induced mechanical allodynia in mice, suggesting the anti-allodynic activities of 1, 2, and 3. This study provides confirmatory evidence for the anti-allodynic activity of purified 1 and also reveals two additional active iridoids from Viticis Fructus. These three iridoids could be potential candidates for the treatment of CIPN.

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Acknowledgements

This study was supported in part by a Grant-in-Aid for the Cooperative Research Project from the Institute of Natural Medicine, University of Toyama in 2016 and 2017; JSPS KAKENHI Grant numbers 15K07993, 15H05268 and 18K06728; Wakanyaku-Biotechnology Research Grant from Toyama prefecture; and JSPS Core-to-Core Program, Asia-Africa Science Platforms. The authors would like to thank Nippon Funmatsu Yakuhin Co., LTD, for providing the extract of Viticis Fructus in large scale.

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Authors and Affiliations

  1. Section of Pharmacognosy, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan

    Huanhuan Yu, Kazufumi Toume & Katsuko Komatsu

  2. Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan

    Yoko Kurokawa & Tsugunobu Andoh

  3. Department of Pharmacology and Pathophysiology, College of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyama-ku, Nagoya, Aichi, 463-8521, Japan

    Tsugunobu Andoh

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Yu, H., Toume, K., Kurokawa, Y. et al. Iridoids isolated from Viticis Fructus inhibit paclitaxel-induced mechanical allodynia in mice. J Nat Med 75, 48–55 (2021). https://doi.org/10.1007/s11418-020-01441-6

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