ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1585181
This article is part of the Research TopicPharmacological Perspectives into Transient Receptor Potential ChannelsView all 6 articles
Identification and Evaluation of a Pinocembrin Analog as a TRPV1 Inhibitor with Analgesic Properties in Murine Pain Models
Provisionally accepted- 1Southern University of Science and Technology, Shenzhen, China
- 2The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
- 3University of Macau, Taipa, Macau Region, China
- 4Hong Kong Polytechnic University, Kowloon, Hong Kong, SAR China
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Pain is a complex phenomenon involving physiological and psychological responses to noxious stimuli. Long-term opioid or NSAID use leads to reduced efficacy and tolerance. Initially a thermosensitive receptor, TRPV1 is increasingly recognized as a target for analgesic intervention. Our investigation is focused on the exploration of novel TRPV1 antagonists derived from natural sources through computational screening methodologies, aiming to assess their efficacy as analgesic agents. Among the compounds screened, a promising TRPV1 antagonist named pinocembrin-7-o-3-o-galloyl-4-6hexahydroxydiphenoyl-beta-d-glucoside (PINO) has exhibited superior stability in its interaction with TRPV1 through virtual screening and molecular dynamics simulation. A dosage of 20 mg/kg of PINO had been shown to reduce the writhing response in acetic acid-induced mice, elevate the thermal pain threshold in the hot water tail-flick and hot plate assays, and concurrently increase the mechanical pain threshold in CFA-induced inflammatory pain models in mice. Moreover, in a murine Lewis lung carcinoma cell line LL-induced bone cancer pain model, PINO also effectively raised the thermal and mechanical pain thresholds in mice. Furthermore, PINO had been found to attenuate the production and gene expression of pro-inflammatory cytokines. The underlying mechanism was attributed to the suppression of NF-κB and MAPK signaling cascades. This innovative compound represents a prospective avenue for the management of acute, chronic, and bone cancer pain, providing a viable alternative analgesic option for individuals suffering from such conditions.
Keywords: Virtual Screening, Molecular Dynamics Simulation, PINO analogue, analgesic, Antiinflammation
Received: 28 Feb 2025; Accepted: 26 May 2025.
Copyright: © 2025 Chen, Li, Deng, Xu, Simon Lee, Nie and Bian. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jin-Song Bian, Southern University of Science and Technology, Shenzhen, China
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