title: Antioxidant efficacy and the upregulation of Nrf2-mediated HO-1 expression by (+)-lariciresinol, a lignan isolated from Rubia philippinensis, through the activation of p38.
abstract: The aim of the present study was to examine the antioxidative activity of (+)-lariciresinol (LRSL), an optically active lignan isolated from Rubia philippinensis in several in vitro assays. LRSL was also subjected to evaluate its inhibitory effect against the generation of reactive oxygen species (ROS) in murine macrophage (RAW 264.7) cells. The results showed that LRSL possessed very strong radical scavenging activity and reducing power, as well as inhibited ROS generation in a dose-dependent manner without showing any cytotoxicity. The transcriptional and translational levels of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were markedly higher in the sample treated group. LRSL treatment also increased the transcriptional and translational activities of NF-E2-related factor-2 (Nrf-2) with a corresponding increase in the transcriptional and translational activities of the heme oxygenase-1 (HO-1). LRSL activated p38 and treatments with SB239063 (a p38 inhibitor) suppressed the LRSL-induced activation of Nrf2, resulting in a decrease in HO-1 expression. Collectively, the data demonstrated that LRSL has potent antioxidative activity, decreasing ROS generation in RAW 264.7 cells and increasing the transcriptional and translational levels of antioxidant enzymes by activating Nrf2-mediated HO-1 induction via p38 signaling.
authors.affiliation: Department of Applied Microbiology and Biotechnology, School of Biotechnology, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Korea.
authors.forename: Vivek K
authors.initials: VK
authors.lastname: Bajpai
authors.affiliation: Department of Food Science and Biotechnology, Graduate School, Kyungpook National University, Daegu 41566, Korea.
authors.forename: Md Badrul
authors.initials: MB
authors.lastname: Alam
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 34134, Korea.
authors.forename: Khong Trong
authors.initials: KT
authors.lastname: Quan
authors.affiliation: Department of Food Science and Biotechnology, Graduate School, Kyungpook National University, Daegu 41566, Korea.
authors.forename: Kyoo-Ri
authors.initials: KR
authors.lastname: Kwon
authors.affiliation: Department of Food Science and Biotechnology, Graduate School, Kyungpook National University, Daegu 41566, Korea.
authors.forename: Mi-Kyoung
authors.initials: MK
authors.lastname: Ju
authors.affiliation: Department of Food Science and Biotechnology, Graduate School, Kyungpook National University, Daegu 41566, Korea.
authors.forename: Hee-Jeong
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Kcellbio, Seoulsoop Kolon Digital Tower, Seongsuil-ro-4-gil, Seongdong-gu, Seoul, 04713, Korea.
authors.forename: Jong Sung
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Kcellbio, Seoulsoop Kolon Digital Tower, Seongsuil-ro-4-gil, Seongdong-gu, Seoul, 04713, Korea.
authors.forename: Jung-In
authors.initials: JI
authors.lastname: Yoon
authors.affiliation: Department of Biological Sciences, Macquarie University, Sydney, NSW 2109, Australia.|Elizabeth Macarthur Agricultural Institute (EMAI), NSW Department of Primary Industries, Menangle, NSW 2567, Australia.
authors.forename: Rajib
authors.initials: R
authors.lastname: Majumder
authors.affiliation: Department of Applied Microbiology and Biotechnology, School of Biotechnology, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Korea.
authors.forename: Irfan A
authors.initials: IA
authors.lastname: Rather
authors.affiliation: Division of Biotechnology, College of Environmental and Bioresource Sciences, Chonbuk National University, 79 Gobong-ro, Iksan-si-570-752, Jeonbuk, Republic of Korea.
authors.forename: Kangmin
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Food Science and Biotechnology, Graduate School, Kyungpook National University, Daegu 41566, Korea.
authors.forename: Sang-Han
authors.initials: SH
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 34134, Korea.
authors.forename: MinKyun
authors.initials: M
authors.lastname: Na
mesh_terms: D000578:Amidines; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D005663:Furans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D050217:Metabolic Detoxication, Phase II; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D000067996:RAW 264.7 Cells; D017382:Reactive Oxygen Species / Q000378:metabolism; D045470:Rubia / Q000737:chemistry*; D015854:Up-Regulation / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000578:Amidines; D000975:Antioxidants; D016166:Free Radical Scavengers; D005663:Furans; D017705:Lignans; D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species; C046728:2,2'-azobis(2-amidinopropane); C060282:lariciresinol; D051547:Heme Oxygenase-1; D048051:p38 Mitogen-Activated Protein Kinases