Ginsenoside Rh1 ameliorates polystyrene nanoplastics-caused vascular injury by regulating HSP70 to suppress endoplasmic reticulum stress and pyroptosis.

INTRODUCTION

The vascular toxicity of polystyrene nanoparticles (PS-Nps) via the circulatory system has emerged as novel critical health risk factors. However, the specific mechanisms underlying PS-Nps-induced vascular endothelial injury and corresponding protective strategies remain poorly understood.

OBJECTIVES

This work seeks to assess the vascular toxicity of PS-Nps and the function and mechanism of rare ginsenoside Rh1 derived from ginseng in alleviating vascular endothelial injury caused by PS-Nps.

METHODS

To dissect the protective mechanisms of Rh1 against PS-Nps-triggered vascular endothelial injury across in vitro and in vivo models, we employed an integrated approach including western blot, immunofluorescence, histopathological staining, siRNA-mediated gene silencing, molecular docking, molecular dynamics simulations, co-immunoprecipitation (Co-IP), surface plasmon resonance (SPR) and cellular thermal shift assay (CETSA). Furthermore, transcriptome sequencing (RNA-seq) was performed to validate the key regulatory pathways involved.

RESULTS

Rh1 inhibited the caspase-1-dependent pyroptosis pathway and NLRP3 inflammasome activation. Importantly, Rh1 exerted its endothelial protective effects by targeting HSP70, thereby suppressing NF-κB p65 nuclear translocation and downregulating endoplasmic reticulum stress (ERS) signaling via GRP78-ATF4-CHOP. Moreover, we further verified that Rh1 effectively alleviates atherosclerosis, reinforcing its translational value in classical cardiovascular disease settings.

CONCLUSION

This research provides the first comprehensive investigation of the protective efficacy of ginsenoside Rh1 for preventing cardiovascular damage induced by the new environmental pollutant PS-Nps. This study provides an innovative theoretical basis for the prevention of cardiovascular diseases related to environmental pollutants by ginseng.