{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:14:00Z","timestamp":1792624440684,"version":"4.5.0"},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,11,28]],"date-time":"2019-11-28T00:00:00Z","timestamp":1574899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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\u2010induced 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\u2010directed 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\u2010induced nociceptive responses and vincristine\u2010induced 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.<\/jats:p>","DOI":"10.1002\/ptr.6559","type":"journal-article","created":{"date-parts":[[2019,11,29]],"date-time":"2019-11-29T04:09:35Z","timestamp":1575000575000},"page":"788-795","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Identification and characterization of saikosaponins as antagonists of transient receptor potential A1 channel"],"prefix":"10.1002","volume":"34","author":[{"given":"Gyeongbeen","family":"Lee","sequence":"first","affiliation":[{"name":"Biocenter, Gyeonggido Business and Science Accelerator  Suwon 16229 South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiwon","family":"Choi","sequence":"additional","affiliation":[{"name":"Bioinformatics and Molecular Design Research Center Yonsei University  Seoul 03722 South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeon\u2010Ju","family":"Nam","sequence":"additional","affiliation":[{"name":"Biocenter, Gyeonggido Business and Science Accelerator  Suwon 16229 South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myung\u2010Jin","family":"Song","sequence":"additional","affiliation":[{"name":"Biocenter, Gyeonggido Business and Science Accelerator  Suwon 16229 South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Kyu","family":"Kim","sequence":"additional","affiliation":[{"name":"Biocenter, Gyeonggido Business and Science Accelerator  Suwon 16229 South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"Biocenter, Gyeonggido Business and Science Accelerator  Suwon 16229 South 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