Natural Products Research Institute, Korea Institute of Science and Technology, 679 Saimdang-ro, Gangneung 25451, Korea.
School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
Int J Mol Sci. 2018 Mar 22;19(4):948. doi: 10.3390/ijms19040948.
Although cisplatin is the standard platinum-based anticancer drug used to treat various solid tumors, it can cause damage in normal kidney cells. Protective strategies against cisplatin-induced nephrotoxicity are, therefore, clinically important and urgently required. To address this challenge, we investigated the renoprotective effects of , a ball-shaped wood-rotting fungus. Chemical investigation of the active fraction from the methanol extract of resulted in the isolation and identification of the renoprotective compounds, hypoxylonol C and F, which ameliorated cisplatin-induced nephrotoxicity to approximately 80% of the control value at 5 μM. The mechanism of this effect was further investigated using hypoxylonol F, which showed a protective effect at the lowest concentration. Upregulated phosphorylation of p38, extracellular signal-regulated kinases, and c-Jun -terminal kinases following cisplatin treatment were markedly decreased after pre-treatment with hypoxylonol F. In addition, the protein expression level of cleaved caspase-3 was significantly reduced after co-treatment with hypoxylonol F. These results show that blocking the mitogen-activated protein kinase signaling cascade plays a critical role in mediating the renoprotective effect of hypoxylonol F isolated from fruiting bodies.
顺铂虽然是一种标准的铂类抗癌药物，用于治疗各种实体瘤，但它会对正常肾细胞造成损伤。因此，针对顺铂诱导的肾毒性的保护策略在临床上非常重要且迫切需要。为了应对这一挑战，我们研究了一种球形木腐真菌——，探讨其对肾脏的保护作用。从甲醇提取物的活性部位中进行化学研究，分离并鉴定出具有肾脏保护作用的化合物hypoxylonol C 和 F，它们在 5μM 时将顺铂诱导的肾毒性改善至接近对照值的 80%。用 hypoxylonol F 进一步研究了这种作用的机制，结果表明该化合物在最低浓度时就具有保护作用。顺铂处理后，p38、细胞外信号调节激酶和 c-Jun 末端激酶的磷酸化水平上调，而用 hypoxylonol F 预处理后明显降低。此外，与 hypoxylonol F 共同处理后，cleaved caspase-3 的蛋白表达水平显著降低。这些结果表明，阻断丝裂原活化蛋白激酶信号级联在介导从 子实体中分离出的 hypoxylonol F 的肾脏保护作用中起关键作用。
Zotero 插件
