Stellaria yunnanensis Franch and its active constituent 20-hydroxyecdysone ameliorate renal failure

Chronic renal failure (CRF) is a progressive disease characterized by a sustained loss of kidney function, for which current therapies remain insufficient. Growing evidence closely links the CRF pathogenesis to renal aging; therefore, targeting aging processes might have therapeutic promise. Herein, we implemented a novel strategy to identify potential anti-CRF agents from anti-aging Chinese herbal medicines. Phenotypic screening indicated that the 75% ethanol extract of Stellaria yunnanensis Franch ( JM11002 ) exhibited marked anti-aging activity, by prolonging the lifespan of Caenorhabditis elegans and decreasing the proportion of SA-β-gal-positive senescent MRC-5 cells. Importantly, JM11002 also ameliorated renal dysfunction, inflammation, and fibrosis in both unilateral ischemia-reperfusion injury (UIRI) and unilateral ureteral obstruction (UUO) mouse models. Phytochemical investigation identified 20-hydroxyecdysone ( JM11201 ), a major active component of JM11002 , which recapitulated the renoprotective effects in both the UUO model and unilateral ischemia-reperfusion injury with contralateral nephrectomy (UIRIx) model. Mechanistically, 20-hydroxyecdysone suppressed the TGF-β1/Smad3 signaling pathway and decreased the expression of fibrosis-related proteins in UUO kidneys. In summary, through an aging-intervention strategy, we discovered the renoprotective effect of Stellaria yunnanensis Franch extract and its active component, 20-hydroxyecdysone, two promising candidates for the development of novel CRF therapies.