Comprehensive regulation of Danggui-Shaoyao-San and its active constituent PGG on puromycin aminonucleoside induced nephrotic syndrome in rats

Background: Danggui-Shaoyao-San (DSS) is a classic Chinese compound prescription that has been proven to be effective in treating nephrotic syndrome (NS) in both clinical trials and animal experiments. This study aimed to reveal the mechanism of action of DSS and one of its main constituents, 1,2,3,4,6-O-pentagalloylglucose (PGG), in protecting the kidney through multiple pathways. Methods: In vivo, we used TUNEL assay, western blotting, real-time quantitative PCR, and immunofluorescence to further confirm the regulatory effects of these interventions on apoptosis, podocyte structure and oedema-related proteins in renal tissue. Results: The results of animal experiments showed that DSS effectively alleviated NS. In different combinations, the blood-associated herbs group and PGG decreased the plasminogen related indicators. Molecular mechanism studies revealed that DSS improved the fusion of podocyte foot processes and inhibited renal cell apoptosis. Furthermore, DSS and PGG were confirmed to have improving effects on sodium transporter related proteins and aquaporin 2. Conclusions: These results demonstrate that DSS can alleviate NS by inhibiting apoptosis, ameliorating podocyte injury and possibly reducing sodium and water retention via plasminogen and that its active constituent PGG has a special effect on plasminogen-epithelial Na⁺ channel, which provides a potential candidate for the treatment of NS.