Cinnamaldehyde ameliorates diabetic kidney disease via anti-inflammatory effects: Bridging traditional use and molecular mechanisms

As one of the most common complications of diabetes, the prevention and treatment of diabetic kidney disease (DKD) has garnered increasing attention. Cinnamaldehyde (CIN), the active component of cinnamon, exhibits anti-inflammatory and anti-diabetic potential, but its role in DKD remains unclear. This study investigated the renoprotective mechanisms of CIN in a streptozotocin (STZ)-induced diabetic rat model. Network pharmacology was employed to predict CIN's targets, and GEO data mining validated that DKD therapeutic targets were associated with inflammation. Animal experiments demonstrated that CIN treatment significantly improved renal function and ameliorated pathological damage. This renoprotection was mechanistically achieved by inhibiting the JAK2/STAT3 signaling pathway, reducing pro-inflammatory M1 macrophage polarization, promoting anti-inflammatory M2 macrophage polarization, and lowering renal inflammation levels, all in a dose-dependent manner. Crucially, the protective effects of CIN were confirmed using the JAK2 inhibitor AG490. In addition, our in vitro experiments further validated that CIN can dose-dependently ameliorate pro-inflammatory M1 macrophage polarization and facilitate anti-inflammatory M2 macrophage polarization by inhibiting the JAK2/STAT3 signaling pathway. Therefore, CIN exerts renoprotective effects in DKD by suppressing JAK2/STAT3 pathway activation and modulating macrophage M1/M2 polarization.