南方医科大学学报2025，Vol.45Issue(11)：2285-2296,12.DOI:10.12122/j.issn.1673-4254.2025.11.01
罗浮山风湿膏药通过抑制TLR4/TNF-α信号通路缓解小鼠神经病理性疼痛
LuoFuShan Rheumatism Plaster ameliorates neuropathic pain in mice by suppressing TLR4/TNF-α signaling
摘要
Abstract
Objective To explore the therapeutic effect of LuoFuShan Rheumatism Plaster(LFS)on neuropathic pain(NP)and its molecular mechanism.Methods Mouse models of sciatic nerve chronic constriction injury(CCI)were treated with low,medium,and high doses(2.2,4.4,and 8.8 cm2,respectively)of LFS by topical application for 14 consecutive days.The therapeutic effects were assessed by evaluating the mechanical withdrawal threshold(MWT),paw withdrawal latency(PWL),plasma IL-6 and TNF-α levels,and histopathology of the sciatic nerve.Network pharmacology and molecular docking were used to identify the key targets and signaling pathways.The key targets were verified by RT-qPCR and immunohistochemistry.The biosafety of LFS was evaluated by measuring the organ indices and damage indicators of the heart,liver,and kidneys.Results Compared with the CCI group,LFS dose-dependently increased MWT and PWL,reduced plasma IL-6 and TNF-α levels,and alleviated sciatic nerve inflammation in the mouse models.Network pharmacology identified 378 bioactive compounds targeting 279 NP-associated genes enriched in TLR and TNF signaling.Molecular docking showed that quercetin and ursolic acid in LFS could stably bind to TLR4 and TNF-α.In the mouse models of sciatic nerve CCI,LFS significantly downregulated the mRNA expression levels of Tlr4 and Tnf-α in the spinal cord in a dose-dependent manner and lowered the protein expressions of TLR4 and TNF-α in the sciatic nerve.LFS treatment did not cause significant changes in the organ indices or damage indicators of the heart,liver and kidneys as compared with those in the CCI model group and sham-operated group.Conclusion LFS alleviates NP in mice by suppression of TLR4/TNF-α-mediated neuroinflammation with a good safety profile.关键词
罗浮山风湿膏药/神经病理性疼痛/TLR4/TNF-α通路/安全性评价Key words
LuoFuShan Rheumatism Plaster/neuropathic pain/TLR4/TNF-α signaling/Safety evaluation引用本文复制引用
傅玉芳,谭伟玲,李小翠,林荣钿,刘叔文,叶玲..罗浮山风湿膏药通过抑制TLR4/TNF-α信号通路缓解小鼠神经病理性疼痛[J].南方医科大学学报,2025,45(11):2285-2296,12.基金项目
Supported by Scientific Connotation of Efficacy of LuoFuShan Rheumatism Plaster Based on Clinical Orientation(K924319081) （K924319081）
National Natural Science Foundation of China(82422077)and Natural Science Foundation of Guangdong Province(2024B1515020093). 基于临床导向的罗浮山风湿膏功效科学内涵研究(K924319081) （82422077）
国家自然科学基金(82422077) （82422077）
广东省自然科学基金(2024B1515020093) （2024B1515020093）
