Wang Wei, Ding Yingzhuo, Yu Chunxia, Chi Qingqing, Fu Xia, Deng Mengjiao, Duan Dongxia, Wei Jinbao, Ding Ronghua, Xi Yufei, Li Qin, Ma Le
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 201108, China; Shanghai Key Laboratory of Psychotic Disorders, Shanghai, 200030, China; Shanghai Institute of Traditional Chinese Medicine for Mental Health, Shanghai, 201108, China.
Shanghai Eye Diseases Prevention &Treatment Center/ Shanghai Eye Hospital, School of Medicine, Tongji University, National Clinical Research Center for Eye Diseases, Shanghai Engineering Research Center of Precise Diagnosis and Treatment of Eye Diseases, NO.1440 Hongqiao Road, Shanghai, 200336, China.
Neuropharmacology. 2025 Aug 1;273:110463. doi: 10.1016/j.neuropharm.2025.110463. Epub 2025 Apr 11.
Neuro-inflammation contributes to neuropathic pain by sensitizing ionic channels. Kinsenoside, a traditional Chinese medicine, has recognized anti-inflammatory properties. However, it remains unclear whether kinsenoside can be used for pain therapy. Network pharmacology analysis revealed that 57 % of its targets are associated with pain, including inflammation and synaptic transmission. The analgesic effects of kinsenoside were confirmed in SNL and formalin rat models, with ED50 values of 47.99 μg and 36.80 μg, respectively. Transcriptome and WGCNA analyses indicated the involvement of cytokine release, anti-inflammatory activity, and synapse enrichment in the blue module. Furthermore, we confirmed that kinsenoside's efficacy was mainly mediated by IL-10 induction, phosphorylation of STAT3, and SOCS3 expression. Pretreatment with kinsenoside significantly inhibited the release of TNF-α, IL-1β, and IL-6. Kinsenoside also attenuated ER stress in both microglia and neural cells. Molecular docking analysis demonstrated significantly high binding energies of IL-10, STAT3, and SOCS3 with MHC. Additionally, whole-cell recordings revealed that bath application of kinsenoside reduced the frequency and amplitude of spinal glutamatergic transmission in a dose-dependent manner. In summary, pharmacological prediction and biological validation collectively indicate that kinsenoside significantly exerts significant analgesic effects by attenuating ER stress and inhibiting inflammatory responses via the IL-10/p-STAT3/SOCS3 axis, precisely regulating spinal glutamatergic transmission for pain relief.
神经炎症通过使离子通道敏感化而导致神经性疼痛。人参皂苷，一种传统中药，具有公认的抗炎特性。然而，人参皂苷是否可用于疼痛治疗仍不清楚。网络药理学分析显示，其57%的靶点与疼痛相关，包括炎症和突触传递。在坐骨神经结扎（SNL）和福尔马林大鼠模型中证实了人参皂苷的镇痛作用，其半数有效量（ED50）值分别为47.99μg和36.80μg。转录组和加权基因共表达网络分析（WGCNA）表明，蓝色模块涉及细胞因子释放、抗炎活性和突触富集。此外，我们证实人参皂苷的疗效主要由白细胞介素-10（IL-10）的诱导、信号转导和转录激活因子3（STAT3）的磷酸化以及细胞因子信号转导抑制因子3（SOCS3）的表达介导。人参皂苷预处理显著抑制肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）的释放。人参皂苷还减轻了小胶质细胞和神经细胞中的内质网应激。分子对接分析表明，IL-10、STAT3和SOCS3与主要组织相容性复合体（MHC）具有显著高的结合能。此外，全细胞记录显示，浴用人参皂苷以剂量依赖性方式降低了脊髓谷氨酸能传递的频率和幅度。总之，药理学预测和生物学验证共同表明，人参皂苷通过减轻内质网应激并通过IL-10/p-STAT3/SOCS3轴抑制炎症反应，精确调节脊髓谷氨酸能传递以缓解疼痛，从而显著发挥镇痛作用。
