Asiatic acid from Centella asiatica alleviates renal fibrosis: coordinated modulation of the gut–kidney axis and retinol metabolism

Chronic kidney disease (CKD) is a progressive condition characterized by renal fibrosis, with limited treatment options. Asiatic acid (AA), a triterpenoid derived from Centella asiatica, has shown renoprotective potential as a dietary supplement. This study integrated 16S rRNA sequencing, renal metabolomics, transcriptomics, and Metorigin analysis to investigate the renoprotective effects of AA in an adenine-induced CKD mouse model. AA significantly improved renal function, attenuated fibrosis, restored gut barrier integrity. Antibiotic depletion experiments demonstrated that an intact gut microbiota is required for the renoprotective effects of AA, supporting a functional link along the gut–kidney axis. AA modulated gut microbiota composition, notably enriching the beneficial genus Lachnospiraceae NK4A136 group. Multi-omics integration identified retinol metabolism as the key renal pathway rescued by AA, with metabolites including 9-cis-retinal and 4-hydroxyretinoic acid (4-OH-RA) showing strong negative correlations with renal injury markers.In vitro, 4-OH-RA suppressed fibrotic injury and oxidative stress in TGF-β1 stimulated tubular cells. These findings suggest that AA alleviates CKD in association with remodeling of the gut microbiota and reprogramming of renal retinol metabolism, highlighting its potential as a microbiota-targeting dietary supplement for renal protection., supporting its potential as a dietary supplement for countering renal fibrosis and supporting kidney health.