Open AccessAntofine suppresses endotoxin‐induced inflammation and metabolic disorder via AMP ‐activated protein kinase
Author(s) -
Chou ShaoTing,
Jung Fang,
Yang ShihHsing,
Chou HweiLing,
Jow GueyMei,
Lin JauChen
Publication year - 2017
Publication title -
pharmacology research and perspectives
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.975
H-Index - 27
ISSN - 2052-1707
DOI - 10.1002/prp2.337
Subject(s) - inflammation , proinflammatory cytokine , ampk , inflammasome , macrophage , microbiology and biotechnology , secretion , protein kinase a , chemistry , pharmacology , biology , kinase , immunology , biochemistry , in vitro
The inhibition of activated macrophages has been used to develop anti‐inflammatory agents for therapeutic intervention to human diseases that cause excessive inflammatory responses. Antofine, a phenanthroindolizidine alkaloid, has a potent anti‐inflammatory effect. However, the molecular mechanisms of its anti‐inflammatory activity have not yet been fully detailed. In this study, we comprehensively explored the anti‐inflammatory effects of antofine on endotoxin‐induced inflammation in macrophages using cDNA microarray analysis, thereby elucidating the potential mechanism by which antofine suppresses inflammation. Antofine significantly suppressed the secretion of proinflammatory cytokines such as TNF α and IL ‐1 β and the production of iNOS in LPS ‐activated Raw264.7 macrophage cells. In addition, antofine can suppress the expressions of several inflammation‐related genes (such as ARG ‐1, IL 1F9, IL ‐10, and IL ‐33) and extracellular matrix genes (such as TNC and HYAL 1), as well as a vasopressor gene ( EDN 1) in activated macrophage cells, that are induced by LPS stimulation. The gene expression profiles analyzed by Gene MANIA software showed that antofine not only contributed anti‐inflammatory activity but also modulated the cellular metabolism via AMPK . Furthermore, antofine also modulated the activation of AMPK and caspase‐1, the key regulator in inflammasome‐mediated IL ‐1 β maturation, in activated macrophage cells. In conclusion, these data indicated that antofine potentially can not only contribute an anti‐inflammatory effect but can also attenuate the metabolic disorders induced by inflammation via AMPK.