title: Curcuminoids distinctly exhibit antioxidant activities and regulate expression of scavenger receptors and heme oxygenase-1.
abstract: METHODS
  Curcumin (CUR), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) have been demonstrated as having antioxidant, anticarcinogenic, and hypocholesterolemic activities. We report the diverse antiatherogenic effects and mechanisms of curcuminoids.
  
  
  RESULTS
  We found that CUR was the most potent antioxidant against copper-mediated LDL oxidation as measured by thiobarbituric acid-reactive substances assay, oxidized LDL (oxLDL) ELISA, and electrophoretic mobility. CUR upregulated heme oxygenase-1, modifier subunit of glutamate-cysteine ligase (GCLM), and CD36 expression in undifferentiated THP-1 cells, supporting the possible involvement of Nrf2 pathway in CD36 expression. Monocyte-to-macrophage differentiation plays a vital role in early atherogenesis. BDMC reduced oxLDL uptake most effectively, while CUR was the best inhibitor for CD36, scavenger receptor A, and lectin-like oxidized LDL receptor-1 expression during phorbol 12-myristate 13-acetate (PMA)-induced THP-1 differentiation. In PMA-differentiated THP-1 macrophages, CUR and DMC effectively induced heme oxygenase-1 expression, but attenuated oxLDL-induced CD36 expression, leading to decreased oxLDL uptake.
  
  
  CONCLUSIONS
  This result indicates curcuminoids, despite structural similarities, exert different atheroprotective effects. Curcuminoids, especially CUR and DMC, are hormetic compounds, which induce Phase II enzyme expression and confer resistance to PMA- and oxLDL-induced scavenger receptor expression and activity.
authors: Department of Biotechnology, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
authors: Mei-Chun
authors: MC
authors: Kou
authors: Shu-Yuan
authors: SY
authors: Chiou
authors: Ching-Yi
authors: CY
authors: Weng
authors: Lisu
authors: L
authors: Wang
authors: Chi-Tang
authors: CT
authors: Ho
authors: Ming-Jiuan
authors: MJ
authors: Wu
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D003300:Copper / Q000378:metabolism; D003474:Curcumin / Q000031:analogs & derivatives / Q000494:pharmacology*; D036381:Diarylheptanoids; D005487:Foam Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000378:metabolism*; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D018955:CD36 Antigens; D036381:Diarylheptanoids; D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D051117:Scavenger Receptors, Class A; D051127:Scavenger Receptors, Class E; D017392:Thiobarbituric Acid Reactive Substances; C099252:oxidized low density lipoprotein; C034786:bisdemethoxycurcumin; C016658:phorbolol myristate acetate; D003300:Copper; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; C546365:GCLM protein, human; D005721:Glutamate-Cysteine Ligase; D003474:Curcumin; D013755:Tetradecanoylphorbol Acetate; C050229:demethoxycurcumin
keywords: CD36; Curcumin; GCLM; HO-1; oxLDL uptake