Ginsenoside Rg1 attenuates T2DM-induced renal damage and fibrosis by inhibiting TRPC6-ChREBP-TXNIP signaling

Ethnopharmacological relevance: As a traditional Chinese medicine, ginseng has many benefits, including regulating blood sugar, blood pressure and so on. Ginsenoside Rg1 is the main active component of ginseng and has been found to significantly improve renal pathological injury in type 2 diabetes mellitus (T2DM) mice. However, the effects and mechanisms of Rg1 in attenuating T2DM are not fully understood.

Aim of the study: This study aims to investigate the role of Rg1 in the treatment of renal damage and fibrosis induced by T2DM and its molecular mechanism.

Materials and methods: T2DM models were constructed on mice and cells respectively and were administered with corresponding drugs. SA-β-Gal and Oil Red O were used to observe cell senescence and lipid droplet deposition; H&E and PAS were used to observe pathological changes in the kidney; masson and sirius red were used to evaluate the level of renal fibrosis. Immunohistochemistry, immunofluorescence and Western blotting were performed to analyze the relevant indexes which resulted in the detection of ROS levels in vitro and in vivo. Calcium imaging was used to test the level of [CA²⁺]_i.

Results: Rg1 and Trpc6 knockout could significantly improve kidney dysfunction, attenuate renal injury and fibrosis and also decrease the expression levels of TRPC6, CaN, TXNIP, ChREBP, p-ASK1 and NLRP3 inflammasome. Meanwhile, Rg1 and Trpc6 knockout significantly inhibited mitochondrial damage and Apoptosis protein release. Additionally, Rg1 treatment has been shown to markedly reduce lipid deposition and ROS accumulation in T2DM, while Trpc6 knockout exhibited no effect on these parameters.

Conclusion: Rg1 treatment can inhibit the TRPC6-ChREBP-TXNIP pathway, thereby improving chronic T2DM-induced renal injury and fibrosis.

Diabetic kidney disease; Ginsenoside Rg1; NLRP3 inflammasome; TRPC6; TXNIP.