Traditional Chinese Herb Couples Mitigate Diabetic Macrovascular Disease Via the AGE‐RAGE Signaling Pathway

Cinnamomi Ramulus‐Puerariae Lobatae Radix (CR‐PLR) possesses antidiabetic macrovascular pathology pharmacological effects, but its pharmacological mechanism of action remains unclear. 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 GO and KEGG analyses showed that CR‐PLR may 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., IL‐6, IL‐4, etc.) and lipid metabolism abnormalities (e.g., TG, TC, LDL, HDL), which was corroborated by the results of immunofluorescence experiments. Western Blot experiments confirmed its action through the AGE‐RAGE pathway. This study may provide an optimized method for elucidating the pharmacological mechanism of CR‐PLR and a new drug candidate for the treatment of diabetic macrovascular disease.