punicalagin and Diabetic-Nephropathies

Diabetic renal injury was associated with dysbiosis of the gut microbiota and intestinal barrier. Punicalagin (PU) from pomegranates potentially impacts the microbial ecosystem, intestinal barrier, and renal function. Therefore, we hypothesized that PU may improve diabetic renal injury by modulating the gut-kidney axis. The present study evaluated the effect of PU on the gut-kidney axis and kidney function in a diabetic renal injury mouse model induced by a high-fat diet (HFD). Mice were fed a HFD without PU or with at doses of 50 and 100 mg kg

Topics: Animals; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Diet, High-Fat; Fatty Acids, Volatile; Gastrointestinal Microbiome; Gene Expression Regulation; Hydrolyzable Tannins; Inflammation; Kidney; Mice; Mice, Inbred C57BL; Pomegranate

Diabetic nephropathy is a diabetic complication caused by chronic inflammation. As the primary polyphenol in pomegranate, punicalagin is believed to have significant anti-inflammatory properties. In this study, we established a mice model for diabetes induced by high-fat diet (HFD)/ streptozotocin (STZ) to verify the protective effect of punicalagin in vivo. The results show that the blood urea nitrogen (BUN), serum creatinine (CREA), and the urine albumin to creatinine ratio (UACR) were significantly decreased in diabetic mice after punicalagin intervention, and the symptoms of glomerular interstitial hyperplasia and glomerular hypertrophy were alleviated. Pyroptosis is an essential manner of programmed cell death in the inflammatory response; the expression of pyroptosis-related proteins such as interleukin-1 (IL-1β), cysteinyl aspartate-specific protease-1 (caspase-1), gasdermin D (GSDMD), and nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing protein 3 (NLRP3) was decreased in our study, which proved that the administration of punicalagin for eight weeks can significantly inhibit pyroptosis in mice. In addition, punicalagin reduced high glucose-mediated protein expressions of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) and alleviated mitochondria damage. Low expression of NOX4 inhibits the dissociation of thioredoxin (Trx) and thioredoxin-interacting protein (TXNIP) and the suppression of NLRP3 inflammasome activation. To summarize, our study provided evidence that punicalagin can alleviate diabetic nephropathy, and the effect is associated with downregulating the expression of NOX4, inhibiting TXNIP/NLRP3 pathway-mediated pyroptosis, suggesting its therapeutic implications for complications of diabetes.

Topics: Albumins; Albuminuria; Animals; Apoptosis; Carrier Proteins; Creatinine; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Diet, High-Fat; Hydrolyzable Tannins; Inflammasomes; Kidney; Male; Mice; Mice, Inbred C57BL; NADPH Oxidase 4; NLR Family, Pyrin Domain-Containing 3 Protein; Protective Agents; Pyroptosis; Serum Albumin; Streptozocin; Thioredoxins