Pharmacological evaluation of physcion as a TRPV1 inhibitor with multimodal analgesic efficacy in experimental pain models
Abstract Background Pain serves as a vital protective mechanism triggered by tissue damage. While NSAIDs and opioids offer relief, their prolonged usage is hindered by adverse effects. Developing analgesics with fewer side effects is crucial for effective pain treatment. The TRPV1 channel is a key t...
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2025-07-01
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| Online Access: | https://doi.org/10.1186/s40659-025-00630-5 |
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| author | Hanbin Chen Guanghong Li Lin Deng Shuli Li Songqiang Huang Simon Ming-Yuen Lee Xiaowei Nie Jin-Song Bian |
| author_facet | Hanbin Chen Guanghong Li Lin Deng Shuli Li Songqiang Huang Simon Ming-Yuen Lee Xiaowei Nie Jin-Song Bian |
| author_sort | Hanbin Chen |
| collection | DOAJ |
| description | Abstract Background Pain serves as a vital protective mechanism triggered by tissue damage. While NSAIDs and opioids offer relief, their prolonged usage is hindered by adverse effects. Developing analgesics with fewer side effects is crucial for effective pain treatment. The TRPV1 channel is a key target for pain relief, with its inhibitors effectively reducing hyperalgesia in animals. This research utilized virtual screening to identify TRPV1-selective natural compounds for potent analgesic properties. Results The physcion exhibited the notable affinity for TRPV1 compared to the compounds examined. After conducting molecular dynamics simulations, physcion emerged as the compound demonstrating the highest binding affinity towards TRPV1, a finding corroborated by calcium imaging, which validated its inhibitory impact. Furthermore, physcion mitigated the stretch number in the acetic acid-induced stretching model, prolonged the latency period in the hot water tail-flick and hot plate assays, and heightened the pain withdrawal threshold lowered by complete Freund’s adjuvant (CFA). Notably, physcion exerted a marked effect in ameliorating bone cancer-induced pain in the hot plate and von Frey tests. Additionally, physcion diminished the levels of inflammatory cytokines and the mRNA expression of both inflammatory and calcium-related genes in the CFA-induced murine model. Furthermore, physcion downregulated the expression of inflammatory genes induced by tumor necrosis factor-α (TNF-α) in RAW264.7 cells. The underlying mechanism potentially involves the suppression of the NF-κB and MAPK signaling cascades. Conclusions Our investigation underscores the potential of physcion as a promising candidate for analgesic therapy. |
| format | Article |
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| institution | Kabale University |
| issn | 0717-6287 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
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| spelling | doaj-art-3e9385bb602444bfadde12ab0f88cbcb2025-08-20T04:01:46ZengBMCBiological Research0717-62872025-07-0158112210.1186/s40659-025-00630-5Pharmacological evaluation of physcion as a TRPV1 inhibitor with multimodal analgesic efficacy in experimental pain modelsHanbin Chen0Guanghong Li1Lin Deng2Shuli Li3Songqiang Huang4Simon Ming-Yuen Lee5Xiaowei Nie6Jin-Song Bian7Department of Pharmacology, Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases, SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and TechnologyDepartment of Pharmacology, Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases, SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and TechnologyDepartment of Cardiology, The Eighth Affiliated Hospital of Sun Yat-sen UniversityState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of MacauSchool of Biomedical Sciences, Affiliated Hospital of Hunan University, Hunan UniversityState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of MacauDepartment of Human Cell Biology and Genetics, School of Medicine, Southern University of Science and TechnologyDepartment of Pharmacology, Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases, SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and TechnologyAbstract Background Pain serves as a vital protective mechanism triggered by tissue damage. While NSAIDs and opioids offer relief, their prolonged usage is hindered by adverse effects. Developing analgesics with fewer side effects is crucial for effective pain treatment. The TRPV1 channel is a key target for pain relief, with its inhibitors effectively reducing hyperalgesia in animals. This research utilized virtual screening to identify TRPV1-selective natural compounds for potent analgesic properties. Results The physcion exhibited the notable affinity for TRPV1 compared to the compounds examined. After conducting molecular dynamics simulations, physcion emerged as the compound demonstrating the highest binding affinity towards TRPV1, a finding corroborated by calcium imaging, which validated its inhibitory impact. Furthermore, physcion mitigated the stretch number in the acetic acid-induced stretching model, prolonged the latency period in the hot water tail-flick and hot plate assays, and heightened the pain withdrawal threshold lowered by complete Freund’s adjuvant (CFA). Notably, physcion exerted a marked effect in ameliorating bone cancer-induced pain in the hot plate and von Frey tests. Additionally, physcion diminished the levels of inflammatory cytokines and the mRNA expression of both inflammatory and calcium-related genes in the CFA-induced murine model. Furthermore, physcion downregulated the expression of inflammatory genes induced by tumor necrosis factor-α (TNF-α) in RAW264.7 cells. The underlying mechanism potentially involves the suppression of the NF-κB and MAPK signaling cascades. Conclusions Our investigation underscores the potential of physcion as a promising candidate for analgesic therapy.https://doi.org/10.1186/s40659-025-00630-5PhyscionVirtual screeningMolecular dynamics simulationAanalgesicAnti-inflammation |
| spellingShingle | Hanbin Chen Guanghong Li Lin Deng Shuli Li Songqiang Huang Simon Ming-Yuen Lee Xiaowei Nie Jin-Song Bian Pharmacological evaluation of physcion as a TRPV1 inhibitor with multimodal analgesic efficacy in experimental pain models Biological Research Physcion Virtual screening Molecular dynamics simulation Aanalgesic Anti-inflammation |
| title | Pharmacological evaluation of physcion as a TRPV1 inhibitor with multimodal analgesic efficacy in experimental pain models |
| title_full | Pharmacological evaluation of physcion as a TRPV1 inhibitor with multimodal analgesic efficacy in experimental pain models |
| title_fullStr | Pharmacological evaluation of physcion as a TRPV1 inhibitor with multimodal analgesic efficacy in experimental pain models |
| title_full_unstemmed | Pharmacological evaluation of physcion as a TRPV1 inhibitor with multimodal analgesic efficacy in experimental pain models |
| title_short | Pharmacological evaluation of physcion as a TRPV1 inhibitor with multimodal analgesic efficacy in experimental pain models |
| title_sort | pharmacological evaluation of physcion as a trpv1 inhibitor with multimodal analgesic efficacy in experimental pain models |
| topic | Physcion Virtual screening Molecular dynamics simulation Aanalgesic Anti-inflammation |
| url | https://doi.org/10.1186/s40659-025-00630-5 |
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