title: A fraction from Dojuksan 30% ethanol extract exerts its anti-inflammatory effects through Nrf2-dependent heme oxygenase-1 expression.
abstract: Dojuksan is a traditional herbal medicine used in Korea and China to treat urinary diseases. In the present study, we aimed to examine the anti-inflammatory effects of an ethanol solvent extract of Dojuksan and a fraction (by bioassay-guided fractionation) derived from this extract, and to elucidate the specific mechanisms involved. The Dojuksan 30% ethanol extract (DEE) had a more significant and potent anti-inflammatory effect than the Dojuksan water extract (DWE). DEE markedly inhibited the production of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), as well as nuclear factor-κB (NF-κB) binding activity. We found that the anti-inflammatory effects of DEE were mediated by the induction of nuclear factor E2-related factor 2 (Nrf2)-dependent heme oxygenase-1 (HO-1). To further explore the anti-inflammatory effects of DEE, we generated 6 different fractions of DEE. Of these, DEE-5 decreased the production of NO more significantly than the other fractions. DEE-5 also significantly decreased the expression of iNOS and COX-2, and the production of NO, PGE2, TNF-α and IL-1β. In addition, DEE-5 also significantly increased HO-1 levels; HO-1 significanlty contributed to the inhibitory effects of DEE-5 on the production of pro-inflammatory mediators. In this study, we determined whether the choice of extraction solvent affects the biological activity of Dojuksan, a traditional herbal formula. Our findings demonstrate that DEE and a fraction derived from this extract exerts anti-inflammatory effects through Nrf2‑dependent HO-1 expression, and that DEE may thus have greater potential therapeutic application than DWE.
authors.affiliation: Department of Biomedical Chemistry, College of Health and Biomedical Science, Konkuk University, Chungju 380-701, Republic of Korea.
authors.forename: Dong-Sung
authors.initials: DS
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Wonkwang University, Iksan 570-749, Republic of Korea.
authors.forename: Kyoung-Su
authors.initials: KS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Wonkwang University, Iksan 570-749, Republic of Korea.
authors.forename: Wonmin
authors.initials: W
authors.lastname: Ko
authors.affiliation: College of Oriental Medicine and Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan 570-749, Republic of Korea.
authors.forename: Gi-Sang
authors.initials: GS
authors.lastname: Bae
authors.affiliation: College of Oriental Medicine and Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan 570-749, Republic of Korea.
authors.forename: Sung-Joo
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Biochemistry, Inha University School of Medicine, Incheon 400-712, Republic of Korea.
authors.forename: Jun-Hyeog
authors.initials: JH
authors.lastname: Jang
authors.affiliation: College of Pharmacy, Wonkwang University, Iksan 570-749, Republic of Korea.
authors.forename: Hyuncheol
authors.initials: H
authors.lastname: Oh
authors.affiliation: College of Pharmacy, Wonkwang University, Iksan 570-749, Republic of Korea.
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
mesh_terms: D000818:Animals; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D053583:Interleukin-1beta / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D016328:NF-kappa B / Q000096:biosynthesis; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D051266:Nuclear Respiratory Factor 1 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D004365:Drugs, Chinese Herbal; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051266:Nuclear Respiratory Factor 1; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; D015232:Dinoprostone