Ginsenoside Rg1 alleviates renal inflammation and fibrosis through regulating Nrf2-TRPC6 signalling pathway in mice

Chronic Kidney Disease (CKD) is a global health issue, with chronic inflammation playing a key role in its progression. This study investigated the protective effects of Ginsenoside Rg1 on LPS-induced renal inflammation and fibrosis in mice, as well as in HMCs. Chronic LPS exposure caused ROS accumulation, TRPC6-mediated calcium overload, and inflammasome activation (AIM2, NLRP1, NLRP3). Trpc6 knockout reduced renal injury and inflammation. Rg1 treatment further mitigated these effects by inhibiting TRPC6-mediated pathways, suppressing inflammasome activation, and enhancing Nrf2/HO-1 signalling to reduce ROS. These results suggest that Rg1 treatment can ameliorate LPS-induced renal inflammation and injury not only by activating Nrf2/HO-1 signalling but also inhibiting TRPC6-mediated inflammasomes activation, thus emerging as a potential agent for attenuating CKD. • Chronic LPS exposure promotes kidney injury and fibrosis formation in mice. • Trpc6 knockout ameliorates renal inflammatory injury through inhibiting calcium overload and inflammasomes activation. • Rg1 alleviates LPS-induced chronic renal inflammation by activating the Nrf2 signalling. • Rg1 attenuates LPS-induced chronic kidney injury by inhibiting TRPC6-inflammasomes signalling.