Renoprotective Effects of Hypoxylonol C and F Isolated from Hypoxylon truncatum against Cisplatin-Induced Cytotoxicity in LLC-PK1 Cells.

Autor: Hwang BS; Natural Products Research Institute, Korea Institute of Science and Technology, 679 Saimdang-ro, Gangneung 25451, Korea. hwang1531@nnibr.re.kr., Lee D; School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea. pjsldh@naver.com., Choi P; Natural Products Research Institute, Korea Institute of Science and Technology, 679 Saimdang-ro, Gangneung 25451, Korea. 090609@kist.re.kr.; College of Korean Medicine, Gachon University, Seongnam 13120, Korea. 090609@kist.re.kr., Kim KS; Natural Products Research Institute, Korea Institute of Science and Technology, 679 Saimdang-ro, Gangneung 25451, Korea. 115042@kist.re.kr., Choi SJ; Natural Products Research Institute, Korea Institute of Science and Technology, 679 Saimdang-ro, Gangneung 25451, Korea. 117045@kist.re.kr., Song BG; Natural Products Research Institute, Korea Institute of Science and Technology, 679 Saimdang-ro, Gangneung 25451, Korea. t16374@kist.re.kr., Kim T; Natural Products Research Institute, Korea Institute of Science and Technology, 679 Saimdang-ro, Gangneung 25451, Korea. kgsing@kist.re.kr., Song JH; Department of Medicine, University of Ulsan College of Medicine, Seoul 05505, Korea. jhsong.john@gmail.com., Kang KS; College of Korean Medicine, Gachon University, Seongnam 13120, Korea. kkang@gachon.ac.kr., Ham J; Natural Products Research Institute, Korea Institute of Science and Technology, 679 Saimdang-ro, Gangneung 25451, Korea. ham0606@kist.re.kr.; Division of Bio-Medical Science and Technology, University of Science and Technology, Daejeon 34113, Korea. ham0606@kist.re.kr.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2018 Mar 22; Vol. 19 (4). Date of Electronic Publication: 2018 Mar 22.
DOI: 10.3390/ijms19040948
Abstrakt: 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 Hypoxylon truncatum , a ball-shaped wood-rotting fungus. Chemical investigation of the active fraction from the methanol extract of H. truncatum 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 N -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 H. truncatum fruiting bodies.
Competing Interests: The authors declare no conflict of interest.
Databáze: MEDLINE