Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 서은경 | * |
dc.date.accessioned | 2021-08-12T16:31:26Z | - |
dc.date.available | 2021-08-12T16:31:26Z | - |
dc.date.issued | 2021 | * |
dc.identifier.issn | 1661-6596 | * |
dc.identifier.other | OAK-29545 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/258660 | - |
dc.description.abstract | Vincristine (VCR) is a widely used chemotherapy drug that induced peripheral painful neuropathy. Yet, it still lacks an ideal therapeutic strategy. The transient receptor potential (TRP) channels, purinergic receptor (P2Y), and mitogen-activated protein kinase (MAPK) signaling play a crucial role in the pathogenesis of neuropathic pain. Withametelin (WMT), a potential Phytosteroid isolated from datura innoxa, exhibits remarkable neuroprotective properties. The present investigation was designed to explore the effect of withametelin on VCR-induced neuropathic pain and its underlying molecular mechanism. Initially, the neuroprotective potential of WMT was confirmed against hydrogen peroxide (H2O2 )-induced PC12 cells. To develop potential candidates for neuropathic pain treatment, a VCR-induced neuropathic pain model was established. Vincristine (75 µg/kg) was ad-ministered intraperitoneally (i.p.) for 10 consecutive days (day 1–10) for the induction of neuropathic pain. Gabapentin (GBP) (60 mg/kg, i.p.) and withametelin (0.1 and 1 mg/kg i.p.) treatments were given after the completion of VCR injection on the 11th day up to 21 days. The results revealed that WMT significantly reduced VCR-induced pain hypersensitivity, including mechanical allodynia, cold allodynia, and thermal hyperalgesia. It reversed the VCR-induced histopathological changes in the brain, spinal cord, and sciatic nerve. It inhibited VCR-induced changes in the biochemical composition of the myelin sheath of the sciatic nerve. It markedly downregulated the expression levels of TRPV1 (transient receptor potential vanilloid 1); TRPM8 (Transient receptor potential melastatin 8); and P2Y nociceptors and MAPKs signaling, including ERK (Extracellular Signal-Regulated Kinase), JNK (c-Jun N-terminal kinase), and p-38 in the spinal cord. It suppressed apoptosis by regulating Bax (Bcl2-associated X-protein), Bcl-2 (B-cell-lymphoma-2), and Caspase-3 expression. It considerably attenuated inflammatory cytokines, oxidative stress, and genotoxicity. This study suggests that WMT treatment suppressed vincristine-induced neuropathic pain by targeting the TRPV1/TRPM8/P2Y nociceptors and MAPK signaling. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. | * |
dc.language | English | * |
dc.publisher | MDPI AG | * |
dc.subject | Bax/Bcl-2 | * |
dc.subject | MAPK | * |
dc.subject | Neuropathic pain | * |
dc.subject | TRPV1/TRPM8 | * |
dc.subject | Vincristine | * |
dc.subject | Withametelin | * |
dc.title | Suppression of TRPV1/TRPM8/p2y nociceptors by withametelin via downregulating mapk signaling in mouse model of vincristine-induced neuropathic pain | * |
dc.type | Article | * |
dc.relation.issue | 11 | * |
dc.relation.volume | 22 | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.journaltitle | International Journal of Molecular Sciences | * |
dc.identifier.doi | 10.3390/ijms22116084 | * |
dc.identifier.wosid | WOS:000660214900001 | * |
dc.identifier.scopusid | 2-s2.0-85107262494 | * |
dc.author.google | Khan A. | * |
dc.author.google | Shal B. | * |
dc.author.google | Khan A.U. | * |
dc.author.google | Ullah R. | * |
dc.author.google | Baig M.W. | * |
dc.author.google | Ul Haq I. | * |
dc.author.google | Seo E.K. | * |
dc.author.google | Khan S. | * |
dc.contributor.scopusid | 서은경(7005953758) | * |
dc.date.modifydate | 20240118144717 | * |