title: Comparative effects of curcuminoids on endothelial heme oxygenase-1 expression: ortho-methoxy groups are essential to enhance heme oxygenase activity and protection.
abstract: Recently, it has been reported that curcumin, which is known as a potent antioxidant, acts as a non- stressful and non-cytotoxic inducer of the cytoprotective heme oxygenase (HO)-1. In this study, naturally occurring curcuminoids, such as pure curcumin, demethoxycurcumin (DMC) and bis-demethoxycurcumin (BDMC), were compared for their potential ability to modulate HO-1 expression and cytoprotective activity in human endothelial cells. All three curcuminoids could induce HO-1 expression and HO activity with differential levels. The rank order of HO activity was curcumin, DMC and BDMC. In comparison with endothelial protection against H2O2-induced cellular injury, cytoprotective capacity was found to be highest with curcumin, followed by DMC and BDMC. Interestingly, cytoprotective effects afforded by curcuminoids were considerably associated with their abilities to enhance HO activity. Considering that the main difference among the three curcuminoids is the number of methoxy groups (none for BDMC, one for DMC, and two for curcumin), the presence of methoxy groups in the ortho position on the aromatic ring was suggested to be essential to enhance HO-1 expression and cytoprotection in human endothelial cells. Our results may be useful in designing more efficacious HO-1 inducers which could be considered as promising pharmacological agents in the development of therapeutic approaches for the prevention or treatment of endothelial diseases caused by oxidative damages.
authors.affiliation: Medicinal Resources Research Institute and Department of Microbiology and Immunology, Wonkwang University, Iksan 570-749, Korea.
authors.forename: Gil Saeng
authors.initials: GS
authors.lastname: Jeong
authors.forename: Gi Su
authors.initials: GS
authors.lastname: Oh
authors.forename: Hyun-Ock
authors.initials: HO
authors.lastname: Pae
authors.forename: Sun-Oh
authors.initials: SO
authors.lastname: Jeong
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
authors.forename: Min-Kyo
authors.initials: MK
authors.lastname: Shin
authors.forename: Byeong Yun
authors.initials: BY
authors.lastname: Seo
authors.forename: Sang Youp
authors.initials: SY
authors.lastname: Han
authors.forename: Ho Sub
authors.initials: HS
authors.lastname: Lee
authors.forename: Jong-Gil
authors.initials: JG
authors.lastname: Jeong
authors.forename: Jeong-Soon
authors.initials: JS
authors.lastname: Koh
authors.forename: Hun-Taeg
authors.initials: HT
authors.lastname: Chung
mesh_terms: D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019610:Cytoprotection / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects; D036381:Diarylheptanoids; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000009:adverse effects; D008954:Models, Biological; D015398:Signal Transduction
chemical_list: D036381:Diarylheptanoids; C034786:bisdemethoxycurcumin; D006861:Hydrogen Peroxide; D051547:Heme Oxygenase-1; D003474:Curcumin; C050229:demethoxycurcumin