Renoprotective Effects of Hypoxylonol C and F Isolated from Hypoxylon truncatum against Cisplatin-Induced Cytotoxicity in LLC-PK1 Cells
- Authors
- Hwang, Buyng Su; Lee, Dahae; Choi, Pilju; Kim, Kyu Sun; Choi, Seon-Jun; Song, Bong Geun; Kim, Taejung; Song, Ji Hoon; Kang, Ki Sung; Ham, Jungyeob
- Issue Date
- Apr-2018
- Publisher
- MDPI
- Keywords
- Hypoxylon truncatum; renoprotective effect; hypoxylonol
- Citation
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.19, no.4
- Journal Title
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
- Volume
- 19
- Number
- 4
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/3919
- DOI
- 10.3390/ijms19040948
- ISSN
- 1422-0067
- Abstract
- 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 mu M. 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.
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