Nano-liposomal berberine and vildagliptin combination: A novel therapeutic approach against oxidative stress, inflammation, autophagy dysregulation, and fibrosis in diabetic nephropathy

An important consequence of diabetes is diabetic nephropathy (DN), which could end up in end-stage renal failure and chronic kidney disease. Blood glucose control, reduction of inflammation, management of oxidative stress, enhancement of autophagy, and repair of renal injury and fibrosis are important strategies for the management of DN. This research examined the protective benefits of berberine hydrochloride liposomes (BHC-Lip) and/or vildagliptin (Vild) against DN in rats with high-fat diet/streptozotocin (HFD/STZ) were examined in this investigation. The rats were separated into four diabetic groups and a control group. These groups are T2DM, T2DM-BHC-Lip, T2DM-Vildagliptin (Vild), and T2DM-BHC-Lip-Vild groups. BHC-Lip or Vild treatment significantly restored antioxidant capacity, resulting in decreased MDA and elevated GPx, SOD, and GSH levels in renal tissues, with combined therapy producing the most powerful effect. The combined therapy significantly improved renal function biomarkers, including creatinine, urea, sodium, and potassium levels, restoring them to nearly control levels. Furthermore, BHC-Lip or Vild treatments markedly reduced serum inflammatory cytokines and upregulated autophagy-related gene expression, with increased expression of Beclin-1 and LC3, and decreased expression of PI3K/Akt/mTOR/P62 signaling. In contrast, combination therapy produced superior autophagic activation and suppression of pro-inflammatory pathways. Furthermore, there was a noticeable improvement in kidney damage and fibrosis indicators (nephrin and higher nestin, desmin, and vimentin), especially those receiving combined treatment. Histopathological examination supported these findings, showing significant improvement in kidney architecture. Together, our findings show that Vild and BHC-Lip work in concert to prevent DN through lowering oxidative stress and inflammation, boosting autophagy, and reducing renal structural damage.