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Ginseng treatment attenuates autophagic cell death in chronic cyclosporine nephropathy
Sun Woo Lim1, Kyoung Chan Doh, Long Jin
1Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea; Transplant Research Center, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
Aims:
Chronic cyclosporine (CsA) treatment induces autophagic cell death characterized by excessive autophagosome formation and decreased autophagic clearance. In this study, we evaluated the influence of ginseng treatment on autophagy in chronic CsA nephropathy.
Methods:
Mice were treated with CsA (30 mg/kg) with or without Korean red ginseng (KRG) extract (0.2, 0.4 g/kg) for 4 weeks. The effect of KRG on CsA-induced autophagosome formation was measured using phospholipid-conjugated form of LC3-II, beclin-1, and autophagic vacuoles were visualized with electron microscopy. Autophagic clearance was evaluated by accumulation of p62/sequestosome 1 (p62) and ubiquitin, then double immunolabeling for p62 and either LC3-II or ubiquitin. To demonstrate the association between the effects of KRG treatment on autophagy and apoptosis, double immunolabelling for LC3-II and active caspase-3 was performed. Multiple autophagy pathways were also examined.
Results:
KRG co-treatment significantly decreased the expression of LC3-II, beclin-1, and the number of autophagic vacuoles compared with the CsA group, and these changes were accompanied by improvements in renal dysfunction and fibrosis. CsA-induced accumulation of p62 and ubiquitin was also decreased by KRG treatment, and these proteins were colocalized with LC3-II and with each other. KRG treatment simultaneously reduced the expression of both active caspase-3 and LC3-II in the injured area. KRG treatment during chronic CsA nephropathy induced the expression of AKT/mTOR, which is a pathway that inhibits autophagy, and reduced AMPK expression.
Conclusion:
Ginseng treatment attenuated CsA-induced excessive autophagosome formation and autophagic aggregates. These findings suggest that ginseng has a renoprotective effect against CsA-induced autophagic cell death.
Insights
Ginseng treatment reduced excessive autophagosome formation and improved kidney function in mice with chronic cyclosporine nephropathy. This suggests ginseng offers protection against drug-induced autophagic cell death.
Area of Science:
- Nephrology
- Cell Biology
- Pharmacology
Background:
- Chronic cyclosporine (CsA) treatment can lead to kidney damage by inducing autophagic cell death, characterized by excessive autophagosome formation and impaired clearance.
- Autophagy, a cellular degradation process, plays a critical role in maintaining kidney health, and its dysregulation is implicated in CsA nephropathy.
Purpose of the Study:
- To investigate the renoprotective effects of Korean red ginseng (KRG) extract on chronic CsA-induced nephropathy.
- To evaluate the influence of KRG on autophagy pathways, including autophagosome formation and clearance, in the context of CsA treatment.
Main Methods:
- Mice received CsA with or without KRG extract for 4 weeks.
- Autophagosome formation was assessed using LC3-II and beclin-1 expression and electron microscopy.
- Autophagic clearance was evaluated by measuring p62/sequestosome 1 (p62) and ubiquitin accumulation, and co-localization studies.
- Apoptosis and autophagy pathway markers (AKT/mTOR, AMPK) were also examined.
Main Results:
- KRG co-treatment significantly reduced LC3-II, beclin-1, and autophagic vacuoles, improving renal dysfunction and fibrosis.
- KRG decreased the accumulation of p62 and ubiquitin, indicating enhanced autophagic clearance.
- KRG treatment reduced both active caspase-3 and LC3-II expression, suggesting a dual effect on apoptosis and autophagy.
- KRG induced the AKT/mTOR pathway and reduced AMPK, modulating autophagy.
Conclusions:
- Ginseng treatment effectively attenuated CsA-induced excessive autophagosome formation and autophagic aggregates.
- These findings highlight ginseng's potential renoprotective effects against CsA-induced autophagic cell death.
- Ginseng may modulate key signaling pathways involved in autophagy regulation, offering therapeutic potential for CsA nephropathy.
