Ginsenoside Rk1 exerts protective effects of LPS-induced podocyte apoptosis and inflammation by inactivating JAK2/STAT3 and NF-κB pathways.

Abstract

Podocyte injury is a major biomarker of primary glomerular disease that leads to massive proteinuria and kidney failure. Ginsenoside Rk1, a substance derived from ginseng, has several pharmacological activities, such as anti-apoptotic, anti-inflammatory, and antioxidant effects. In this study, our goal is to investigate the roles and mechanisms of ginsenoside Rk1 in podocyte injury and acute kidney injury (AKI). C57BL/6 mice were intraperitoneally injected with 10 mg/kg LPS to mimic AKI-like conditions in vivo. One hour after the LPS challenge, ginsenoside Rk1 (10 mg/kg or 20 mg/kg) or vehicle was orally administered into mice every 6 h until sacrifice at 24 h. Renal functions were assessed by measuring blood urea nitrogen and creatinine. Renal histological changes were examined by hematoxylin and eosin staining. The production of proinflammatory cytokines in kidney tissues was evaluated by RT-qPCR and western blotting. A conditionally immortalized mouse MPC-5 podocyte cell line was treated with LPS and ginsenoside Rk1. Viability and apoptosis of MPC-5 cells were estimated by CCK-8 and flow cytometry. Western blotting was also conducted to measure the protein levels of apoptosis-related and pathway-related genes. The results of abovementioned experiments revealed that Ginsenoside Rk1 ameliorated LPS-stimulated podocyte apoptosis in vitro and relieved renal dysfunctions and inflammatory response in LPS-induced AKI mice. Mechanistically, ginsenoside Rk1 inactivated the JAK2/STAT3 and NF-κB pathways in LPS-treated podocytes and mice. In conclusion, this study shows that Ginsenoside Rk1 attenuates LPS-induced renal dysfunctions and inflammatory response in mice and LPS-induced podocyte apoptosis in vitro through inactivating the NF-κB and JAK2/STAT3 pathways.