title: Berberine inhibits NADPH oxidase mediated superoxide anion production in macrophages.
abstract: Oxidative stress and amplified redox signaling contribute to the pathogenesis of many human diseases including atherosclerosis. The superoxide-generating phagocytic NADPH oxidase is a key source of oxidative stress in the developing atheroma. The aim of the present study was to examine the effect of berberine, a plant-derived alkaloid, on NADPH oxidase-mediated superoxide anion production in macrophages. Lipopolysaccharide (LPS) treatment activated NADPH oxidase in THP-1 monocyte-derived macrophages and increased the intracellular level of superoxide anions. Preincubation of cells with berberine demonstrated a concentration-dependent (10-50 micromol/L) and time-dependent (6-24 h) inhibition of superoxide anion generation in LPS-stimulated macrophages. Cell viability tests confirmed that berberine, at concentrations sufficient for inhibiting NADPH oxidase-mediated superoxide anion generation in macrophages, did not affect cell viability. Real-time PCR analysis revealed that addition of berberine to the culture medium was able to reduce gp91phox mRNA expression in LPS-treated cells. Berberine also restored superoxide dismutase (SOD) activity, which was found to be inhibited by LPS treatment. In conclusion, results from the present study demonstrate that berberine can effectively reduce intracellular superoxide levels in LPS- stimulated macrophages. Such a restoration of cellular redox by berberine is mediated by its selective inhibition of gp91phox expression and enhancement of SOD activity. The therapeutic relevance of berberine in the prevention and management of atherosclerosis remains to be further investigated.
authors.affiliation: St Boniface Hospital Research Centre, Winnipeg, MB R2H 2A6, Canada.
authors.forename: Lindsei K
authors.initials: LK
authors.lastname: Sarna
authors.forename: Nan
authors.initials: N
authors.lastname: Wu
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Hwang
authors.forename: Yaw L
authors.initials: YL
authors.lastname: Siow
authors.forename: Karmin
authors.initials: K
authors.lastname: O
mesh_terms: D001599:Berberine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D008562:Membrane Glycoproteins; D001599:Berberine; D013481:Superoxides; D013482:Superoxide Dismutase; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C086986:CYBA protein, human