Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 757, Issue -, Pages 1-10Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2015.03.013
Keywords
Berberine; Src; Toll-like receptor; Macrophage migration
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Funding
- National Health Research Institute [NHRI-EX104-10420BI]
- National Science Council [NSC102-2325-B-006-010, NSC101-2311-B-039-002-MY3]
- Taiwan Department of Health Clinical Trial and Research Center of Excellence [DOH102-TD-B-111-004]
- China Medical University [DWR-100-021]
- National Research Program for Genomic Medicine Grants of NSC [NSC 94-3112-B-001-003, NSC 94-3112-B-001-018-Y]
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Berberine is an isoquinoline with anti-inflammatory activity. We previously demonstrated that there was a loop of signal amplification between nuclear factor kappa B and Src for macrophage mobility triggered by the engagement of Toll like receptors (TLRs). The simultaneous suppression of lipopoly-saccharicle (LPS) mediated upregulation of inducible nitric oxide synthase, cyclooxygenase 2, and cell mobility in berberine-treated macrophages suggested Sic might be a target of berberine. Indeed, th reduced migration, greatly suppressed Sic induction in both protein and RNA transcript by berberine were observed in macrophages exposed to LPS, peptidoglycan, polyinosinic-polycytidylic acid, and CpG-oligodeoxynucleotides. In addition to Sic induction, berberine also inhibited LPS-mediated Sic activation in Sic overexpressing macrophages and S-nitroso-N-acetylpenicillamine (a nitric oxide donor) could partly restore it. Moreover, berberine suppressed Sic activity in fibronectin-stimulated macrophages and in v-Src transformed cells. These results implied that by effectively reducing Sic expression and activity, berberine inhibited TLR-mediated cell motility in macrophages. (C) 2015 Elsevier B.V. All rights reserved.
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