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

Abstract

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.

TNF-α from the Proximal Nephron Exacerbates Aristolochic Acid Nephropathy

“… 50 , 51 Human proximal tubular epithelial (HK-2) cells treated with AA have decreased levels of ATP production, mitochondrial membrane depolarization, and cytochrome C release. 52 , 53 Jiang et al 54 reported that respiratory control ratios and ATP content are reduced in tubular cells by AA treatment in a dose-dependent manner, highlighting dysfunction of mitochondrial energy metabolism in the nephron. In our current in vitro studies with primary kidney tubular cells, the basal levels of cellular respiration are quite low and actually rise rather than fall with AA exposure.…”

Some Common Medicinal Plants with Antidiabetic Activity, Known and Available in Europe (A Mini-Review)

“…Moreover, it improves blood circulation as well as protects against illnesses of the respiratory and nervous systems. It also improves liver activity, physical endurance, and bone metabolism and ensures the neutralization of changes in postmenopausal osteoporosis [178][179][180][181][182][183][184][185]. It is generally believed that ginseng improves metabolism and, thus, helps to improve and maintain good health, and, for this reason, it is an ingredient of dietary supplements [186].…”

Combined use of Panax notoginseng and leech provides new insights into renal fibrosis: Restoration of mitochondrial kinetic imbalance

“…Previous studies have revealed that comprehensive saponins derived from Panax notoginseng have a remarkable ability to modulate mitochondrial energy metabolism, oxidative stress, biosynthesis, and apoptosis [ 14 ]. Furthermore, these saponins have shown significant potential in impeding the progression of renal fibrosis in various animal models of renal failure [ 16 – 18 ]. Leech (Whitmania pigra whitman; Chinese Pinyin: Shui Zhi), renowned for their therapeutic properties in enhancing blood circulation and alleviating blood stasis, have been utilized in medical applications [ 19 ].…”

“…Previous studies have revealed that comprehensive saponins derived from Panax notoginseng have a remarkable ability to modulate mitochondrial energy metabolism, oxidative stress, biosynthesis, and apoptosis [14]. Furthermore, these saponins have shown significant potential in impeding the progression of renal fibrosis in various animal models of renal failure [16][17][18].…”