4.6 Article

Berberine, A Phytoalkaloid, Inhibits Inflammatory Response Induced by LPS through NF-Kappaβ Pathway: Possible Involvement of the IKKα

Journal

MOLECULES
Volume 26, Issue 16, Pages -

Publisher

MDPI
DOI: 10.3390/molecules26164733

Keywords

berberine; THP-1 cells; lipopolysaccharide; NF-kappa B; 5TL; anti-inflammation

Funding

  1. University of Tennessee College of Pharmacy Drug Discovery Center
  2. Departmental maintenance, CREBB, FIST, UPE, PURSE

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Berberine has been shown to possess therapeutic properties in various health conditions, including anti-inflammatory effects by inhibiting NF-kappa B translocation in activated monocytes. This suggests its potential for treating chronic inflammatory disorders.
Berberine (BBR), a plant alkaloid, is known for its therapeutic properties of anticancer, cardioprotective, antidiabetic, hypolipidemic, neuroprotective, and hepatoprotective activities. The present study was to determine the molecular mechanism of BBR's pharmacological activity in human monocytic (THP-1) cells induced by arachidonic acid (AA) or lipopolysaccharide (LPS). The effect of BBR on AA/LPS activated proinflammatory markers including TNF-alpha, MCP-1, IL-8 and COX-2 was measured by ELISA or quantitative real-time PCR. Furthermore, the effect of BBR on LPS-induced NF-kappa B translocation was determined by immunoblotting and confocal microscopy. AA/ LPS-induced TNF-alpha, MCP-1, IL-6, IL-8, and COX-2 markers were markedly attenuated by BBR treatment in THP-1 cells by inhibiting NF-kappa B translocation into the nucleus. Molecular modeling studies suggested the direct interaction of BBR to IKK alpha at its ligand binding site, which led to the inhibition of the LPS-induced NF-kappa B translocation to the nucleus. Thus, the present study demonstrated the anti-inflammatory potential of BBR via NF-kappa B in activated monocytes, whose interplay is key in health and in the pathophysiology of atherosclerotic development in blood vessel walls. The present study findings suggest that BBR has the potential for treating various chronic inflammatory disorders.

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