Zhankuic acid a isolated from taiwanofungus camphoratus is a novel selective TLR4/MD-2 antagonist with anti-inflammatory properties

Yu Fon Chen, Ai Li Shiau, Sheng Hung Wang, Jai Sing Yang, Sue Joan Chang, Chao Liang Wu, Tian Shung Wu

研究成果: Article同行評審

20 引文 斯高帕斯(Scopus)

摘要

TLR4, a membrane receptor that functions in complex with its accessory protein myeloid differentiation factor-2 (MD-2), is a therapeutic target for bacterial infections. Taiwanofungus camphoratus is highly valued as a medicinal mushroom for cancer, hypertension, and inflammation in traditional medicine. Zhankuic acid A (ZAA) is the major pharmacologically active compound of T. camphoratus. The mechanism of action of T. camphoratus or ZAA has not been fully elucidated. We analyzed the structure of human TLR4/MD-2 complex with ZAA by X-score and HotLig modeling approaches. Two Abs against MD-2 were used to verify the MD-2/ZAA interaction. The inflammation and survival of the mice pretreated with ZAA and injected with LPS were monitored. The modeling structure shows that ZAA binds the MD-2 hydrophobic pocket exclusively via specific molecular recognition; the contact interface is dominated by hydrophobic interactions. Binding of ZAA to MD-2 reduced Ab recognition to native MD-2, similar to the effect of LPS binding. Furthermore, ZAA significantly ameliorated LPS-induced endotoxemia and Salmonella-induced diarrhea in mice. Our results suggest that ZAA, which can compete with LPS for binding to MD-2 as a TLR4/ MD-2 antagonist, may be a potential therapeutic agent for gram-negative bacterial infections. The Journal of Immunology, 2014, 192: 2778-2786.

原文English
頁(從 - 到)2778-2786
頁數9
期刊Journal of Immunology
192
發行號6
DOIs
出版狀態Published - 2014 三月 15

All Science Journal Classification (ASJC) codes

  • 免疫學和過敏
  • 免疫學

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