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: Jae Ho Choi, Sun Woo Jin, Hyung Gyun Kim, Tilak Khanal, Yong Pil Hwang, Kyung Jin Lee, Chul Yung Choi, Young Chul Chung, Young Chun Lee, Hye Gwang Jeong
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 56 Pg. 231-9 (Jun 2013) ISSN: 1873-6351 [Electronic] England
• PMID: 23485615 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Actins
• Antioxidants
• Changkil
• Collagen Type I
• NF-E2-Related Factor 2
• NF-kappa B
• Nfe2l2 protein, rat
• Plant Extracts
• RNA, Messenger
• TIMP1 protein, rat
• Tissue Inhibitor of Metalloproteinase-1
• Tumor Necrosis Factor-alpha
• smooth muscle actin, rat
• Malondialdehyde
• Heme Oxygenase (Decyclizing)
• Hmox1 protein, rat
• Cyclooxygenase 2
• Ptgs2 protein, rat
• NAD(P)H Dehydrogenase (Quinone)
• NQO1 protein, rat
• Glutathione Transferase
• Aspartate Aminotransferases
• Alanine Transaminase
• Matrix Metalloproteinase 13
• Mmp13 protein, rat
• Glutamate-Cysteine Ligase
• Dimethylnitrosamine

Topics

• Actins (metabolism)
• Alanine Transaminase (blood)
• Animals
• Antioxidants (pharmacology)
• Aspartate Aminotransferases (blood)
• Collagen Type I (metabolism)
• Cyclooxygenase 2 (metabolism)
• Dimethylnitrosamine (adverse effects)
• Glutamate-Cysteine Ligase (metabolism)
• Glutathione Transferase (metabolism)
• Heme Oxygenase (Decyclizing) (metabolism)
• Hep G2 Cells
• Humans
• Lipid Peroxidation (drug effects)
• Liver (drug effects, enzymology, pathology)
• Liver Cirrhosis (chemically induced, drug therapy, pathology)
• Male
• Malondialdehyde (blood)
• Matrix Metalloproteinase 13 (metabolism)
• NAD(P)H Dehydrogenase (Quinone) (metabolism)
• NF-E2-Related Factor 2 (metabolism)
• NF-kappa B (antagonists & inhibitors, metabolism)
• Plant Extracts (pharmacology)
• Plant Roots (chemistry)
• Platycodon
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Tissue Inhibitor of Metalloproteinase-1 (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)