Unraveling the superiority of (−)‐gallocatechin gallate to (−)‐epigallocatechin‐3‐gallate in protection of diabetic nephropathy of db/db mice

Abstract

AbstractGCG ((−)‐gallocatechin gallate) and EGCG ((−)‐epigallocatechin‐3‐gallate) are main biologically active polyphenolic compounds in tea leaves, and EGCG has been studied for its potential effects on alleviating diabetic nephropathy (DN). Previous studies showed that GCG exhibited better hypoglycemic and antioxidant efficacy than EGCG. However, the efficacy and molecular mechanisms of GCG in the protection of DN are unknown. In this study, db/db mice were administered with EGCG or GCG orally for 20 weeks to comparatively investigate their effects on DN. These results revealed that GCG was significantly more effective than EGCG in decreasing water intake and urine excretion, reducing fasting blood glucose levels and systolic blood pressure, improving mesenteric artery contractility, enhancing the right renal hemodynamics, and improving key renal function markers. Through transcriptome analysis, S100A8/S100A9, two regulators of interstitial fibrosis, were identified and found to be more sensitive to GCG intervention, which was further confirmed by mRNA and protein expression data. In addition, the molecular docking analysis results demonstrated that GCG displayed a superior binding affinity toward S100A8/S100A9 in comparison to EGCG. Overall, our study found that GCG holds significant potential for the treatment of DN and outperforms EGCG in terms of efficacy.