Niao-Du-Kang granules regulate autophagy of diabetic nephropathy via the miR-214-3p/SIRT1 signaling pathway.

Ethnopharmacological Relevance: Niao-Du-Kang (NDK) granules, a traditional Chinese medicinal preparation composed of eight different types of herbs, and have been utilized in the treatment of chronic kidney disease for many years, yet its molecular mechanisms of action in diabetic nephropathy (DN) remain to be elucidated.

Aim Of The Study: This study aimed to investigate the therapeutic potential of NDK granules in diabetic nephropathy (DN), with a focus on their impact on autophagy regulation, particularly through the miR-214-3p/SIRT1 pathway.

Materials And Methods: The DN mouse model was established through a high-fat feeding combined with streptozotocin (STZ) injection. After 4 weeks of gavage, fasting blood glucose, blood lipids, blood urea nitrogen, and serum creatinine were measured. Renal histopathological alterations were evaluated through HE, PAS and Masson staining, while the expression of miR-214-3p, SIRT1, autophagy related proteins and inflammatory cytokines were detected by qRT-PCR and Western blot in renal tissues and in vitro models. For in vitro experiments, mesangial cells were stimulated with 30 μg/mL lipopolysaccharide (LPS) for 24 h, followed by treatment with NDK-containing serum; cell viability was measured by Cell Counting Kit-8 (CCK-8) assay. The direct interaction between SIRT1 and miR-214-3p was confirmed by dual luciferase reporter assays and miRNA mimic/inhibitor transfections experiments.

Results: NDK granules significantly improved renal function, promoted renal autophagy, upregulated SIRT1 levels, and downregulated miR-214-3p expression in the kidney of DN mice. NDK-containing serum effectively inhibited mesangial cell proliferation, inflammatory response, and autophagy impairment in vitro. Furthermore, miR-214-3p inhibition potentiated the regulatory effects of NDK granules on SIRT1 and autophagy-related proteins, whereas miR-214-3p overexpression attenuated these therapeutic effects. The direct targeting relationship of miR-214-3p and SIRT1 was further confirmed using dual-luciferase reporter assays.

Conclusions: NDK granules have been shown to exert a protective effect on autophagy impairment in diabetic kidneys by modulating the miR-214-3p/SIRT1 pathway, suggesting a promising avenue for novel clinical treatment strategies for DN.