Shenkang injection ameliorates peritoneal fibrosis via the ESR1/PI3K/Akt pathway: Experimental verification and network pharmacology analysis.

BACKGROUND

Peritoneal fibrosis (PF) is the most distressing complication for peritoneal dialysis (PD) patients, leading to ultrafiltration failure and forcing discontinuation of PD. However, no effective treatment is currently available. Shenkang injection (SKI) is a traditional Chinese medicine which has shown anti-fibrosis efficacy. This study focused on the validation and preliminary prediction of the role and molecular mechanisms of SKI against PF.

METHODS

The PF mouse model in vivo and cellular mesothelial-mesenchymal transition (MMT) model in vitro were conducted to verify whether SKI had mitigating fibrosis and anti-MMT effects. Mass spectrometry was used to collect and analyze the major compounds of SKI. Then we examine the potential targets and underlying mechanisms through network pharmacology analysis and molecular docking. Finally, in vitro experiments were performed to validate the function of SKI on signaling pathways.

RESULTS

The in vivo and in vitro experimental data showed that SKI alleviated the progression of PF. Further mass spectrometry and network pharmacology analysis revealed that the active compounds in SKI may bind to ESR1 and prevent its nuclear translocation, hence inhibiting the activation of the PI3K-Akt signaling pathway. Experimental validation of SKI inhibited high glucose (HG)-induced activation of the ESR1/PI3K/Akt pathway.

CONCLUSIONS

This study examines the therapeutic effect of SKI on PF and provides preliminary experimental support for further clinical investigation of SKI against PF.