School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
College of Korean Medicine, Gachon University, Seongnam 13120, Korea.
Int J Mol Sci. 2018 Jan 7;19(1):174. doi: 10.3390/ijms19010174.
Platinum-based anticancer drug therapies can cause renal damage and apoptotic kidney cell damage. The development of reno- and kidney-protective molecules is therefore urgently required. To address this challenge, we explored secondary metabolites of termite-associated sp. RB1 isolated from the cuticle of the South African termite, for their renoprotective ability using bioassay-guided fractionation and LLC-PK1 cells. Chemical investigation of the MeOH extract of sp. RB1 resulted in the isolation and identification of a renoprotective metabolite, 1--(2-aminobenzoyl)-α-l-rhamnopyranoside (ABR) () from the active fraction, which ameliorated cisplatin-induced cytotoxicity to 80% of the control value at 25 μM. Upregulated phosphorylation of c-Jun N-terminal kinases (JNK) and p38 following cisplatin treatment was markedly decreased after pre-treatment of cells with ABR. In addition, levels of cleaved caspase-3 and the percentage of apoptotic cells were also significantly reduced after pre-treatment with ABR. These findings provide experimental evidence that blocking the MAPK signaling cascade plays a critical role in mediating the renoprotective effect of ABR, which may inspire the development of novel therapeutic substances to prevent anticancer drug-induced nephrotoxicity.
基于铂的抗癌药物治疗会导致肾脏损伤和凋亡的肾细胞损伤。因此，迫切需要开发肾和肾脏保护分子。为了应对这一挑战，我们使用基于生物测定的分级分离和 LLC-PK1 细胞，探索了从南非白蚁表皮中分离出的与白蚁相关的 sp. RB1 的次生代谢产物，以研究其肾脏保护能力。 sp. RB1 的 MeOH 提取物的化学研究导致从活性部分分离并鉴定出一种肾脏保护代谢物，1--(2-氨基苯甲酰基)-α-l-鼠李吡喃糖苷（ABR）（），在 25 μM 时将顺铂诱导的细胞毒性改善至对照值的 80%。在用 ABR 预处理细胞后，顺铂处理后 JNK 和 p38 的磷酸化明显减少。此外，用 ABR 预处理后，cleaved caspase-3 的水平和凋亡细胞的百分比也显著降低。这些发现为阻断 MAPK 信号级联在介导 ABR 的肾脏保护作用方面发挥关键作用提供了实验证据，这可能为开发预防抗癌药物诱导的肾毒性的新型治疗物质提供启示。
