Network pharmacology and experimental validation of asiaticoside protecting against diabetic kidney disease by regulating 11β-hydroxysteroid dehydrogenase type 2

OBJECTIVE: To explore the protective effects and mechanisms of Asiaticoside (AC) against diabetic kidney disease (DKD) through network pharmacology combined with in vitro and in vivoexperiments. METHODS: Based on network pharmacology and RNA sequencing (RNA-Seq) analyses, combined with molecular docking, the core targets and signaling pathways of AC in the treatment of DKD were predicted and screened. Subsequently, the therapeutic effect of AC on DKD was validated in db/db mice and SV40-MES-13 cells, and its molecular mechanism was evaluated. RESULTS: Network pharmacology and protein-protein interaction analyses identified 11-beta hydroxysteroid dehydrogenase type 2 (HSD11B2) as a potential key target for AC treatment of DKD. Molecular docking indicated strong affinity between AC derivative and HSD11B2. RNA-Seq analysis showed that AC significantly regulated steroid metabolism under diabetic conditions. In db/db mice, AC reduced urinary protein excretion, improved renal morphology, and protected renal function. AC also dose-dependently inhibited excessive proliferation of SV40-MES-13 cells in a high-glucose environment. Further validation showed that AC upregulated Hsd11b2 mRNA expression and HSD11B2 protein levels. CONCLUSION: AC may alleviate DKD-related pathological processes by regulating Hsd11b2 gene expression and HSD11B2 protein levels.