Ginsenoside Rg1 Ameliorates Acute Renal Ischemia/Reperfusion Injury via Upregulating AMPK1 Expression.

Acute renal ischemia/reperfusion (I/R) injury often occurs during kidney transplantation and other kidney surgeries, and the molecular mechanism involves oxidative stress. We hypothesized that ginsenoside Rg1 (Rg1), a saponin derived from ginseng, would protect the renal tissue against acute renal I/R injury by upregulating 5' adenosine monophosphate-activated protein kinase 1 (AMPK1) expression and inhibiting oxidative stress. The models of acute anoxia/reoxygenation (A/R) damage in normal rat kidney epithelial cell lines (NRK-52E) and acute renal I/R injury in mice were constructed. The results revealed that pretreatment with 25 M Rg1 significantly increased NRK-52E viability, decreased lactate dehydrogenase (LDH) activity and apoptosis, suppressed reactive oxygen species generation and oxidative stress, stabilized mitochondrial membrane potential and reduced mitochondria permeability transition pore openness, decreased adenosine monophosphate/adenosine triphosphate ratio, and upregulated the expression of AMPK1, cytochrome b-c1 complex subunit 2, NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 8, and B-cell lymphoma 2, while downregulating BCL2-associated X protein expression. The effects of Rg1 pretreatment were similar to those of pAD/Flag-AMPK1. After acute renal I/R injury, serum creatinine, blood urea nitrogen, LDH activity, and oxidative stress in renal tissue significantly increased. Rg1 pretreatment upregulated AMPK1 expression, which protects against acute renal I/R injury by maintaining renal function homeostasis, inhibiting oxidative stress, and reducing apoptosis. Compound C, a specific inhibitor of AMPK, reversed the effects of Rg1. In summary, Rg1 pretreatment upregulated AMPK1 expression, inhibited oxidative stress, maintained mitochondrial function, improved energy metabolism, reduced apoptosis, and ultimately protected renal tissue against acute renal I/R injury.