title: Luteolin and luteolin-7-O-glucoside strengthen antioxidative potential through the modulation of Nrf2/MAPK mediated HO-1 signaling cascade in RAW 264.7 cells.
abstract: It has been understood that glycosidic forms of flavonoids were hydrolyzed by gut bacteria and absorbed as aglycones. However, several reports suggested that glycosides were partly absorbed without hydrolysis and remained biologically active. In this study, we evaluated the antioxidative potential of luteolin and luteolin-7-O-glucoside, glycosidic form of luteolin, against the oxidative damage and compared their antioxidative mechanisms in RAW 264.7 cells. Heme oxygenase-1 (HO-1), one of the phase II enzymes showing an antioxidative activity, was potently induced by luteolin and luteolin-7-O-glucoside treatment, which was in accordance with the translocated nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) into nucleus. Moreover, luteolin and the luteolin-7-O-glucoside activated HO-1 expression by p38 and c-Jun NH2-terminal kinase (JNK) regulation. In order to identify the antioxidation potential by HO-1, tert-butyl hydroperoxide (t-BHP)-induced oxidative damage was applied and ameliorated by luteolin and the luteolin-7-O-glucoside treatment in a dose dependent manner, which was confirmed by HO-1 selective inhibitor and inducer, tin protoporphyrin (SnPP) and cobalt protoporphyrin (CoPP), respectively. Consequently, luteolin and luteolin-7-O-glucoside potently strengthen the HO-1-mediated antioxidative potential through the modulation of the Nrf2/MAPK signaling pathways.
authors.affiliation: Department of Smart Foods and Drugs, Inje University, Gimhae, Gyeongnam, Republic of Korea.
authors.forename: Young Sun
authors.initials: YS
authors.lastname: Song
authors.affiliation: Department of Clinical Laboratory Science, Dong-Eui University, Busan, Republic of Korea. Electronic address: cmpark@deu.ac.kr.
authors.forename: Chung Mu
authors.initials: CM
authors.lastname: Park
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D005960:Glucosides / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D047311:Luteolin / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D005960:Glucosides; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; C066408:luteolin-7-glucoside; D051547:Heme Oxygenase-1; D047311:Luteolin
keywords: Heme oxygenase-1; Luteolin; Luteolin-7-O-glucoside; Mitogen activated protein kinase; Nuclear factor-erythroid 2 p45-related factor 2