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.
Key words
apoptosis - aristolochic acids - HK-2 cells -
Panax ginseng
- Araliaceae - proliferation - regeneration
