Identification and characterization of saikosaponins as antagonists of transient receptor potential A1 channel

Gyeongbeen Lee, Jiwon Choi, Yeon Ju Nam, Myung Jin Song, Jin Kyu Kim, Woo Jung Kim, Pansoo Kim, Jong Suk Lee, Songmi Kim, Kyoung Tai No, Ji Hyun Lee, Jin Koo Lee, Yongmun Choi

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1 Citation (Scopus)


Neuropathic pain is associated with an increased sensitivity to painful stimuli or abnormal sensitivity to otherwise innocuous stimuli. However, in addition to adverse effects, currently available drugs have shown limited response in patients with neuropathic pain, which provides a rationale to explore new drug classes acting on novel targets and with better efficacy and safety profiles. Here, we found that saikosaponins potently inhibit agonist-induced activation of the transient receptor potential A1 (TRPA1) channel, which has been reported to mediate neuropathic pain by sensing a variety of chemical irritants. Molecular docking and site-directed mutagenesis analyses suggested that saikosaponins bind to the hydrophobic pocket in TRPA1 near the Asn855 residue, which, when mutated to Ser, was previously associated with enhanced pain perception in humans. In support of these findings, saikosaponin D significantly attenuated agonist-induced nociceptive responses and vincristine-induced mechanical hypersensitivity in mice. These results indicate that saikosaponins are TRPA1 antagonists and provide a basis for further elaboration of saikosaponin derivatives for the development of new therapeutics for neuropathic pain.

Original languageEnglish
Pages (from-to)788-795
Number of pages8
JournalPhytotherapy Research
Issue number4
Publication statusPublished - 2020 Apr 1

Bibliographical note

Funding Information:
This work was supported by Support Program for Creative Industry Institutes (R0003950, MOTIE, Korea) and by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MIST) (No. 2016R1A5A2007009). We would also like to acknowledge the generous financial support from the Gyeonggi provincial government.

All Science Journal Classification (ASJC) codes

  • Pharmacology

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