title: Platycodi Radix attenuates dimethylnitrosamine-induced liver fibrosis in rats by inducing Nrf2-mediated antioxidant enzymes.
abstract: The purpose of this study was to investigate the anti-fibrotic effects of the aqueous extract of the Platycodi Radix root (Changkil: CK) on dimethylnitrosamine (DMN)-induced liver fibrosis in rats. DMN treatment for 4 weeks led to marked liver fibrosis as assessed by serum biochemistry, histopathological examination, and hepatic lipid peroxidation and collagen content. CK significantly inhibited DMN-induced increases in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, fibrosis score, and hepatic malondialdehyde and collagen content. CK also inhibited DMN-induced reductions in rat body and liver weights. Reverse transcription polymerase chain reaction (RT-PCR) and western blot analyses revealed that CK inhibited DMN-induced increases in matrix metalloproteinase-13 (MMP-13), tissue inhibitor of metalloproteinase-1 (TIMP-1), and tumor necrosis factor-α (TNF-α) mRNA, and collagen type I and α-smooth muscle actin protein. DMN-induced cyclooxygenase-2 (COX-2) expression and nuclear factor-kappa B (NF-κB) activation was reduced by CK treatment. Furthermore, CK induced activation of nuclear erythroid 2-related factor 2 (Nrf2)-mediated antioxidant enzymes such as γ-glutamylcysteine synthetase (γ-GCS), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), and glutathione-S-transferase (GST) in HepG2 cells. These results demonstrated that CK attenuates DMN-induced liver fibrosis through the activation of Nrf2-mediated antioxidant enzymes.
authors.affiliation: Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Choi
authors.forename: Sun Woo
authors.initials: SW
authors.lastname: Jin
authors.forename: Hyung Gyun
authors.initials: HG
authors.lastname: Kim
authors.forename: Tilak
authors.initials: T
authors.lastname: Khanal
authors.forename: Yong Pil
authors.initials: YP
authors.lastname: Hwang
authors.forename: Kyung Jin
authors.initials: KJ
authors.lastname: Lee
authors.forename: Chul Yung
authors.initials: CY
authors.lastname: Choi
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Chung
authors.forename: Young Chun
authors.initials: YC
authors.lastname: Lee
authors.forename: Hye Gwang
authors.initials: HG
authors.lastname: Jeong
mesh_terms: D000199:Actins / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D024042:Collagen Type I / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004128:Dimethylnitrosamine / Q000009:adverse effects*; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D031238:Platycodon; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000199:Actins; D000410:Alanine Transaminase; D000975:Antioxidants; D001219:Aspartate Aminotransferases; D024042:Collagen Type I; D051546:Cyclooxygenase 2; D004128:Dimethylnitrosamine; D005721:Glutamate-Cysteine Ligase; D005982:Glutathione Transferase; D006419:Heme Oxygenase (Decyclizing); D008315:Malondialdehyde; D053509:Matrix Metalloproteinase 13; D016660:NAD(P)H Dehydrogenase (Quinone); D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D010936:Plant Extracts; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; C440574:Changkil; C495637:Nfe2l2 protein, rat; C576839:TIMP1 protein, rat; C498862:Acta2 protein, rat; C491523:Hmox1 protein, rat; C489691:Ptgs2 protein, rat; C507703:NQO1 protein, rat; C507083:Mmp13 protein, rat