Ameliorative effect of white tea from 50-year-old tree of Camellia sinensis L. (Theaceae) on kidney damage in diabetic mice via SIRT1/AMPK pathway

Diabetic kidney damage (DKD) is one of the most common complications of diabetes, which is known as a chronic inflammatory kidney disease caused by persistent hyperglycemia . White tea was originally used as a folk medicine to treat measles in ancient China. What arouses our interest is that there is a traditional method to treat diabetes with white tea taken from over 30-year-old tree of Camellia sinensis L. However, there are few reports on the renal protection of white tea. This present study was designed to study the potential protective effects of white tea (WT) and old tree white tea (OTWT) on high-fat-diet (HFD) combined with streptozotocin (STZ)-induced type 2 diabetic mice to explore the possible mechanism of WT/OTWT against DKD. C57BL/6 mice were randomly divided into four groups: NC, T2D , WT (400 mg/kg·b.w, p.o.), OTWT (400 mg/kg·b.w, p.o.). Diabetes was established in all groups except NC group, by six weeks of HFD feeding combined with STZ (50 mg/kg, i.p.) for 3 times, treatments were administered for six weeks and then all the animals were decapitated; kidney tissues and blood samples were collected for the further analysis, including: levels of insulin, lipid metabolism (TG, TC, HDL, LDL, FFA), antioxidative enzymes (catalase (CAT), super oxide dismutase (SOD), glutathione peroxidase (GPx)), blood urea nitrogen (BUN) and creatine , inflammatory cytokines (TNF-α, IL-1β, COX-2, iNOS , MCP-1), advanced glycation end products (AGE), receptor of AGE (RAGE), Nrf2, AMPK, SIRT1 , and PGC-1α. H&E, PAS and Masson staining were performed to examine the histopathological alterations of the kidneys. Our data showed that WT and OTWT reversed the abnormal serum lipids (TG, TC, HDL, LDL, FFA) in T2D mice, upregulated antioxidative enzymes levels (CAT, SOD, GPx) and inhibit the excessive production of proinflammatory mediators (including MCP-1, TNF-α, IL1β, COX-2 and iNOS) by varying degrees, and OTWT was more effective. In histopathology, OTWT could significantly alleviate the accumulation of renal AGE in T2D mice, thereby improving the structural changes of the kidneys, such as glomerular hypertrophy , glomerular basement membrane thickening and kidney FIbrosis . Both WT and OTWT could alleviate the diabetic changes in T2D mice via hypoglycemic , hypolipidemic , anti-oxidative and anti-inflammatory effects, while OTWT was more evident. OTWT could prominently alleviate the accumulation of AGE in the kidneys of T2D mice, thereby ameliorating the renal oxidative stress and inflammatory damage, which was associated with the activation of SIRT1/AMPK pathway.