Bunel Valérian, Antoine Marie-Hélène, Nortier Joëlle, Duez Pierre, Stévigny Caroline
Laboratory of Experimental Nephrology, Faculty of Medicine, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Laboratory of Pharmacognosy, Bromatology and Human Nutrition, Faculty of Pharmacy, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Planta Med. 2015 Mar;81(5):363-72. doi: 10.1055/s-0035-1545839. Epub 2015 Mar 23.
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.
这项体外研究旨在确定人参提取物对马兜铃酸介导的HK-2细胞毒性的影响。人参甲醇提取物（50μg/mL）能够在50μM马兜铃酸处理24、48和72小时后降低细胞存活率，刃天青还原试验证明了这一点。通过使用膜联蛋白V-碘化丙啶染色进行细胞凋亡的流式细胞术评估证实了该结果，并且表明与单独使用马兜铃酸相比，用马兜铃酸和人参提取物处理的细胞凋亡率更高。然而，人参提取物本身（5和50μg/mL）增加了Ki-67指数，表明细胞增殖增强。细胞周期分析排除了人参提取物介导的G2/M细胞周期阻滞诱导，如通常在马兜铃酸中观察到的那样。最后，发现当用两种剂量的人参处理细胞时，β-连环蛋白的获得加速，这表明肾近端小管上皮细胞的上皮表型得以维持。此外，人参处理（5和50μg/mL）在24和48小时后降低了马兜铃酸诱导的氧化应激活性。这些结果表明，人参提取物对马兜铃酸诱导的细胞毒性活性氧的产生具有保护作用。然而，人参介导的氧化应激减轻与马兜铃酸诱导的细胞凋亡和死亡的减少无关，而是与增加有关。这种有害的草药-草药相互作用可能会使马兜铃酸肾小管毒性恶化，并加重损伤的严重程度和持续时间。尽管如此，细胞增殖和迁移的增加，以及上皮表型维持的改善，表明人参可能有助于改善肾小管再生和药物性肾损伤后的恢复。人参的这种双重活性当然值得进一步的体内研究。
