Phloretin alleviates renal injury in streptozotocin-induced diabetic mice through NF-κB/MAPK signaling pathways.
Source: PubMed, NCBI / U.S. National Library of Medicine
Diabetic nephropathy (DN) is a complication of diabetes characterized by renal dysfunction, fibrosis, and inflammation. This study aimed to investigate the nephroprotective effects of phloretin (PHL) in a streptozotocin (STZ)-induced diabetic mouse model. Mice were treated with PHL (50 mg/kg/day) for eight weeks, after which renal function parameters, oxidative stress markers, histopathological changes, fibrosis- and inflammation-related protein expression, and key signaling pathways were analyzed. The results demonstrated that PHL ameliorated hyperglycemia, renal dysfunction (as evidenced by reduced BUN, serum creatinine, and urinary albumin), and dyslipidemia (lowered serum TG and TC). PHL also attenuated renal oxidative stress by enhancing antioxidant enzyme activities (SOD, CAT, GSH-Px) and reducing lipid peroxidation (MDA). Histopathological evaluation revealed that PHL alleviated glomerular damage, tubular necrosis, and inflammatory cell infiltration, while Masson's staining showed inhibition of renal interstitial fibrosis. Mechanistically, PHL downregulated the expression of fibrosis markers (fibronectin, collagen I, α-SMA) and proinflammatory cytokines (IL-6, IL-1β, TNF-α). Furthermore, PHL suppressed the activation of the NF-κB and MAPK pathways, as indicated by increased IκBα levels and reduced phosphorylation of NF-κB p65, p38, JNK, and ERK1/2. In conclusion, PHL protects against DN by improving renal function, reducing oxi
Abstract
Diabetic nephropathy (DN) is a complication of diabetes characterized by renal dysfunction, fibrosis, and inflammation. This study aimed to investigate the nephroprotective effects of phloretin (PHL) in a streptozotocin (STZ)-induced diabetic mouse model. Mice were treated with PHL (50 mg/kg/day) for eight weeks, after which renal function parameters, oxidative stress markers, histopathological changes, fibrosis- and inflammation-related protein expression, and key signaling pathways were analyzed. The results demonstrated that PHL ameliorated hyperglycemia, renal dysfunction (as evidenced by reduced BUN, serum creatinine, and urinary albumin), and dyslipidemia (lowered serum TG and TC). PHL also attenuated renal oxidative stress by enhancing antioxidant enzyme activities (SOD, CAT, GSH-Px) and reducing lipid peroxidation (MDA). Histopathological evaluation revealed that PHL alleviated glomerular damage, tubular necrosis, and inflammatory cell infiltration, while Masson's staining showed inhibition of renal interstitial fibrosis. Mechanistically, PHL downregulated the expression of fibrosis markers (fibronectin, collagen I, α-SMA) and proinflammatory cytokines (IL-6, IL-1β, TNF-α). Furthermore, PHL suppressed the activation of the NF-κB and MAPK pathways, as indicated by increased IκBα levels and reduced phosphorylation of NF-κB p65, p38, JNK, and ERK1/2. In conclusion, PHL protects against DN by improving renal function, reducing oxidative stress, mitigating fibrosis and inflammation, and inactivating the NF-κB/MAPK pathways.