Isoquercitrin Alleviates Diabetic Nephropathy by Inhibiting STAT3 Phosphorylation and Dimerization.

ABSTRACT: At the convergence point of multiple cytokine signals, signal transducer and activator of transcription 3 (STAT3) is a highly promising therapeutic target for diabetic nephropathy. Isoquercitrin, a natural small-molecule inhibitor of STAT3, may have beneficial effects on diabetic nephropathy; however, the underlying mechanism remains unclear. Isoquercitrin significantly mitigated renal inflammation and fibrosis by inhibiting STAT3 activity in mice with diabetic nephropathy. Moreover, STAT3 is a direct molecular target of isoquercitrin, which as corroborated by tight and stable noncovalent binding between them. This interaction is mechanistically supported by the affinity of isoquercitrin for the Ser668-Gln635-Gln633 region within the pY+1 binding pocket of the SH2 domain. This binding obst

SUBMITTER: Xuan C 

PROVIDER: S-EPMC12224983 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature