Hirsutanol A attenuates lipopolysaccharide-mediated matrix metalloproteinase 9 expression and cytokines production and improves endotoxemia-induced acute sickness behavior and acute lung injury

Jing Shiun Jan, Chih Hao Yang, Mong Heng Wang, Fan Li Lin, Jing Lun Yen, Irene Hsieh, Maksim Khotimchenko, Tzong Huei Lee, George Hsiao

研究成果: 雜誌貢獻文章

1 引文 斯高帕斯(Scopus)

摘要

Activated human monocytes/macrophages, which increase the levels of matrix metalloproteinases (MMPs) and pro-inflammatory cytokines, are the essential mechanisms for the progression of sepsis. In the present study, we determined the functions and mechanisms of hirsutanolA (HA), which is isolated from the red alga-derived marine fungus Chondrostereum sp. NTOU4196, on the production of pro-inflammatory mediators produced from lipopolysaccharide (LPS)-treated THP-1 cells. Our results showed that HA suppressed LPS-triggered MMP-9-mediated gelatinolysis and expression of protein and mRNA in a concentration-dependent manner without effects on TIMP-1 activity. Also, HA significantly attenuated the levels of TNF-α, IL-6, and IL-1β from LPS-treated THP-1 cells. Moreover, HA significantly inhibited LPS-mediated STAT3 (Tyr705) phosphorylation, IκBα degradation and ERK1/2 activation in THP-1 cells. In an LPS-induced endotoxemia mouse model, studies indicated that HA pretreatment improved endotoxemia-induced acute sickness behavior, including acute motor deficits and anxiety-like behavior. HA also attenuated LPS-induced phospho-STAT3 and pro-MMP-9 activity in the hippocampus. Notably, HA reduced pathologic lung injury features, including interstitial tissue edema, infiltration of inflammatory cells and alveolar collapse. Likewise, HA suppressed the induction of phospho-STAT3 and pro-MMP-9 in lung tissues. In conclusion, our results provide pharmacological evidence that HA could be a useful agent for treating inflammatory diseases, including sepsis.
原文英語
文章編號360
期刊Marine Drugs
17
發行號6
DOIs
出版狀態已發佈 - 六月 17 2019

ASJC Scopus subject areas

  • Drug Discovery

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