title: In vitro effects of Panax ginseng in aristolochic acid-mediated renal tubulotoxicity: apoptosis versus regeneration.
abstract: This in vitro study aimed to determine the effects of a Panax ginseng extract on aristolochic acid-mediated toxicity in HK-2 cells. A methanolic extract of ginseng (50 µg/mL) was able to reduce cell survival after treatment with 50 µM aristolochic acid for 24, 48, and 72 h, as evidenced by a resazurin reduction assay. This result was confirmed by a flow cytometric evaluation of apoptosis using annexin V-PI staining, and indicated higher apoptosis rates in cells treated with aristolochic acid and P. ginseng extract compared with aristolochic acid alone. However, P. ginseng extract by itself (5 and 50 µg/mL) increased the Ki-67 index, indicating an enhancement in cellular proliferation. Cell cycle analysis excluded a P. ginseng extract-mediated induction of G2/M cell cycle arrest such as the one typically observed with aristolochic acid. Finally, β-catenin acquisition was found to be accelerated when cells were treated with both doses of ginseng, suggesting that the epithelial phenotype of renal proximal tubular epithelial cells was maintained. Also, ginseng treatment (5 and 50 µg/mL) reduced the oxidative stress activity induced by aristolochic acid after 24 and 48 h. These results indicate that the ginseng extract has a protective activity towards the generation of cytotoxic reactive oxygen species induced by aristolochic acid. However, the ginseng-mediated alleviation of oxidative stress did not correlate with a decrease but rather with an increase in aristolochic acid-induced apoptosis and death. This deleterious herb-herb interaction could worsen aristolochic acid tubulotoxicity and reinforce the severity and duration of the injury. Nevertheless, increased cellular proliferation and migration, along with the improvement in the epithelial phenotype maintenance, indicate that ginseng could be useful for improving tubular regeneration and the recovery following drug-induced kidney injury. Such dual activities of ginseng certainly warrant further in vivo studies.
authors: Laboratory of Experimental Nephrology, Faculty of Medicine, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors: Valérian
authors: V
authors: Bunel
authors: Laboratory of Experimental Nephrology, Faculty of Medicine, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors: Marie-Hélène
authors: MH
authors: Antoine
authors: Laboratory of Experimental Nephrology, Faculty of Medicine, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors: Joëlle
authors: J
authors: Nortier
authors: Laboratory of Pharmacognosy, Bromatology and Human Nutrition, Faculty of Pharmacy, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors: Pierre
authors: P
authors: Duez
authors: Laboratory of Pharmacognosy, Bromatology and Human Nutrition, Faculty of Pharmacy, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors: Caroline
authors: C
authors: Stévigny
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D030022:Aristolochia / Q000737:chemistry; D034341:Aristolochic Acids / Q000009:adverse effects*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D004347:Drug Interactions; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints; D036145:Ginsenosides / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects; D005894:Panax / Q000737:chemistry*; D008517:Phytotherapy; D010936:Plant Extracts / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D034341:Aristolochic Acids; D036145:Ginsenosides; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D051176:beta Catenin; C000228:aristolochic acid I; D053148:Caspase 3