Li Jing, Li Xiaoliang, Zhai Hongyan, Wu Deling, Chu Xiaoqin
School of Pharmacy, Anhui University of Chinese Medicine, Hefei, China.
Anhui Joyfar Pharmaceutical Research Institute Co. Ltd., Hefei, China.
Chem Biodivers. 2025 Apr 3:e202500531. doi: 10.1002/cbdv.202500531.
Cinnamomi Ramulus-Puerariae Lobatae Radix (CR-PLR) possesses antidiabetic macrovascular pathology pharmacological effects, but its precise pharmacological mechanisms remain to be fully elucidated. A total of 197 CR-PLR targets were identified, with 1015 diabetic macrovascular disease-specific targets through network pharmacological analysis, and 55 intersecting targets were found. We screened five main active ingredients: Puerarin, 3'-methoxydaidzein, cinnamaldehyde, cinnamic acid, and formononetin. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that CR-PLR might ameliorate diabetic macrovascular disease through the AGE-RAGE signaling pathway. In vivo experiments verified that CR-PLR significantly reduced body weight and blood glucose, improved vascular function, and attenuated inflammatory responses (e.g., interleukin-6 [IL-6], IL-4, etc.) and lipid metabolism abnormalities (e.g., triglyceride, total cholesterol, LDL, HDL), which was corroborated by the results of immunofluorescence experiments. WB analysis validated that CR-PLR modulates the AGE-RAGE signaling pathway, thereby attenuating vascular inflammation and metabolic dysregulation. These findings provide novel insights into the therapeutic potential of CR-PLR, suggesting its application as a complementary treatment for diabetic macrovascular disease.
桂枝-葛根（CR-PLR）具有抗糖尿病大血管病变的药理作用，但其确切的药理机制仍有待充分阐明。通过网络药理学分析共鉴定出197个CR-PLR靶点，其中有1015个糖尿病大血管疾病特异性靶点，发现了55个交集靶点。我们筛选出五种主要活性成分：葛根素、3'-甲氧基大豆苷元、肉桂醛、肉桂酸和芒柄花素。基因本体论和京都基因与基因组百科全书分析表明，CR-PLR可能通过AGE-RAGE信号通路改善糖尿病大血管疾病。体内实验证实，CR-PLR显著降低体重和血糖，改善血管功能，并减轻炎症反应（如白细胞介素-6 [IL-6]、IL-4等）和脂质代谢异常（如甘油三酯、总胆固醇、低密度脂蛋白、高密度脂蛋白），免疫荧光实验结果也证实了这一点。蛋白质免疫印迹分析验证了CR-PLR调节AGE-RAGE信号通路，从而减轻血管炎症和代谢失调。这些发现为CR-PLR的治疗潜力提供了新的见解，表明其可作为糖尿病大血管疾病的辅助治疗方法。
