The Ginsenoside Rg₁ Rescues Mitochondrial Disorders in Aristolochic Acid-Induced Nephropathic Mice

Chronic exposure to aristolochic acid (AA) leads to renal interstitial fibrosis and nephropathy. In this study, we aimed to investigate the renoprotective effects of Panax ginseng extract (GE) and ginsenoside saponin (GS) on AA-induced nephropathy (AAN) in mice. Eighty female C3H/He mice were randomly divided into eight groups, including normal; AA (3 μg/mL for 56 days); AA with GE (125, 250, or 500 mg/kg/d for 14 days); and AA with important GE ingredients, Rg₁, Rb₁, or Rd (5 mg/kg/d for 14 days). Compared with the AA group, renal injuries were significantly decreased in the GE (250 mg/kg/d), Rb₁, and Rg₁ treatment groups. Rg₁ exhibited the best renoprotection among all GS-treated groups. There were 24 peaks significantly altered among normal, AA, and AA + Rg₁ groups, and four mitochondrial proteins were identified, including acyl-CoA synthetase medium-chain family member 2, upregulated during skeletal muscle growth 5 (Usmg5), mitochondrial aconitase 2 (ACO2), and cytochrome c oxidase subunit Va preprotein (COX5a). We demonstrated for the first time that the AAN mechanism and renoprotective effects of Rg₁ are associated with expression of mitochondrial proteins, especially ACO2, Usmg5, and COX5a.