Chen Peng-Fei, Huang Guang-Xiao, Gu Wen-Ting, Zhuang Guo-Dong, Chen Chong, Wang Shu-Mei, Tang Dan
Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administration of TCM and Engineering & Technology Research Center for Chinese Materia Medica Quality of Guangdong Province, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
Chem Biodivers. 2024 Sep;21(9):e202400910. doi: 10.1002/cbdv.202400910. Epub 2024 Aug 6.
Diabetic peripheral neuropathy (DPN) is a significant and frequent complication of diabetes. Bu-Yang-Huan-Wu Decoction (BHD) is a classic traditional Chinese herbal prescription that is commonly used in modern clinical practice for the effective treatment of DPN, but the underlying mechanism is not yet clearly defined. The chemical constituents of BHD were characterized by UPLC-Q-Orbitrap HR MS/MS, and a total of 101 chemical components were identified, including 30 components absorbed into blood. An interaction network of "compound-target-disease" interactions was constructed based on the compounds detected absorbed in blood and their corresponding targets of diabetic neuropathy acquired from disease gene databases, and the possible biological targets and potential signalling pathways of BHD were predicted via network pharmacology analysis. Subsequently, methylglyoxal-induced (MGO-induced) Schwann cells (SCs) were used to identify the active ingredients in blood components of BHD and verify the molecular mechanisms of BHD. Through network topological analysis, 30 shared targets strongly implicated in the anti-DPN effects of BHD were identifed. Combined network pharmacology and in vitro cellular analysis, we found that the active ingredient of BHD may treat DPN by modulating the AGEs/RAGE pathway. This study provides valuable evidence for future mechanistic studies and potential therapeutic applications for patients with DPN.
糖尿病周围神经病变(DPN)是糖尿病一种常见且严重的并发症。补阳还五汤(BHD)是一种经典的中药方剂,在现代临床实践中常用于有效治疗DPN,但其潜在机制尚未明确。采用超高效液相色谱-四极杆-轨道阱高分辨质谱联用技术(UPLC-Q-Orbitrap HR MS/MS)对BHD的化学成分进行表征,共鉴定出101种化学成分,其中30种成分可吸收入血。基于检测到的吸收入血的化合物及其从疾病基因数据库中获取的糖尿病神经病变相应靶点,构建了“化合物-靶点-疾病”相互作用网络,并通过网络药理学分析预测了BHD可能的生物学靶点和潜在信号通路。随后,利用甲基乙二醛诱导(MGO诱导)的雪旺细胞(SCs)来鉴定BHD血成分中的活性成分,并验证BHD的分子机制。通过网络拓扑分析,确定了30个与BHD抗DPN作用密切相关的共同靶点。结合网络药理学和体外细胞分析,我们发现BHD的活性成分可能通过调节晚期糖基化终末产物/晚期糖基化终末产物受体(AGEs/RAGE)途径治疗DPN。本研究为未来DPN患者的机制研究和潜在治疗应用提供了有价值的证据。