Meng Jun, Zhang Zhenglang, Wang Yujie, Long Lina, Luo Anqi, Luo Zhenhui, Cai Kexin, Chen Xi, Nie Hong
Guangzhou Baiyunshan Pharmaceutical Holdings Co., Ltd. Baiyunshan Hejigong Pharmaceutical Factory, NO. 52 Xiaogang Dama Road, Xinshi Street, Baiyun District, Guangzhou, 510410, China.
State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE) of China, College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou, 510632, China.
Purinergic Signal. 2024 Nov 4. doi: 10.1007/s11302-024-10056-5.
An increasing number of traditional Chinese medicine(TCM) have been confirmed to possess analgesic bioactivity. 701 Dieda Zhentong patch(701-DZP) which includes 14 kinds of TCMs exhibited excellent efficacy in alleviating back or leg pain after a soft-tissue injury. In this study, UPLC/MS was used to construct the fingerprint of 701-DZP and excavate the potential bioactive ingredients of it. 21 compounds were detected and identified in the fingerprint including 12 compounds that pass through the skin and 6 compounds observed in the plasma. Then, the role of 701-DZP in neuropathic pain(NPP) was assessed by network pharmacology and CCI rats. 701-DZP inhibited pain sensitization(MWT and TWL) and the release of inflammation mediators(IL-1β and IL-6) in CCI rats which were in keeping with the core targets of the PPI network. The results of IHC and Western blot showed that the expression of the P2X3 receptor in the DRG and SC of CCI rats was significantly reduced after the treatment with 701-DZP. Moreover, the 701-DZP down-regulated the level of phosphorylation of ERK1/2 MAPK instead of P38 MAPK in the DRG of CCI rats. In conclusion, this study has clarified 6 potential analgesic active compounds of 701-DZP and explored the analgesic properties, which may inhibit the expression of the P2X3 receptor to reduce the release of inflammatory mediators based on the ERK1/2 MAPK pathway to alleviate the NPP.
越来越多的中药已被证实具有镇痛生物活性。包含14种中药的701跌打镇痛膏（701-DZP）在缓解软组织损伤后的腰腿痛方面显示出优异疗效。在本研究中，采用超高效液相色谱/质谱联用技术构建701-DZP的指纹图谱并挖掘其潜在生物活性成分。在指纹图谱中检测并鉴定出21种化合物，其中包括12种透过皮肤的化合物以及6种在血浆中检测到的化合物。然后，通过网络药理学和坐骨神经慢性缩窄损伤（CCI）大鼠评估701-DZP在神经性疼痛（NPP）中的作用。701-DZP抑制了CCI大鼠的疼痛敏化（机械缩足阈值和热缩足潜伏期）以及炎症介质（白细胞介素-1β和白细胞介素-6）的释放，这与蛋白质-蛋白质相互作用（PPI）网络的核心靶点一致。免疫组化和蛋白质免疫印迹结果显示，701-DZP治疗后，CCI大鼠背根神经节（DRG）和脊髓（SC）中P2X3受体的表达显著降低。此外，701-DZP下调了CCI大鼠DRG中细胞外信号调节激酶1/2（ERK1/2）丝裂原活化蛋白激酶的磷酸化水平，而非P38丝裂原活化蛋白激酶的磷酸化水平。总之，本研究阐明了701-DZP的6种潜在镇痛活性化合物，并探索了其镇痛特性，其可能通过抑制P2X3受体的表达，基于ERK1/2丝裂原活化蛋白激酶途径减少炎症介质的释放，从而减轻神经性疼痛。
