Moutan Cortex terpene glycoside improves diabetic kidney disease by down-regulating SIRT1 mediated autophagy pathway

Moutan Cortex terpene glycoside was derived from the dried root bark of <em>Paeonia suffruticosa Andr.</em> in the Paeoniaceae family, which holds significant value as a traditional Chinese medicine.<strong> </strong>This study investigated that Moutan Cortex terpene glycoside improves diabetic kidney disease (DKD) by targeting sirtuin 1 (SIRT1) mediated autophagy pathway. Mechanistic insights are gained using DKD model rats and human umbilical vein endothelial cells (HUVECs) to delineate how Moutan Cortex terpene glycoside operates in the treatment of DKD. Furthermore, network pharmacology is used to identify the primary metabolic pathways affected by Moutan Cortex terpene glycoside, with key targets being confirmed through PCR (Polymerase Chain Reaction), Western blot, Transmission electron microscope, immunofluorescence staining and Monodansylcadaverine (MDC) staining. Finally, small interfering RNA transfection testified SIRT1 in advanced glycation end-products (AGEs)-induced HUVECs injury. Moutan Cortex terpene glycoside effectively decreased blood glucose rise in DKD rats and improvements and reduced levels of cytokines and biochemical indicators. Network pharmacology revealed that metabolism was the main pathway of Moutan Cortex, and the main targets were verified by PCR and protein experiments. Based on these results, we found that Moutan Cortex could improve DKD and SIRT1 was a potential target. Furthermore, knockdown of SIRT1 attenuated AGEs-induced the expression of Beclin 1 and LC3II/I in HUVECs. In summary, this study demonstrated that Moutan Cortex could alleviate DKD via down-regulating SIRT1-mediated autophagy pathway.