title: Hepatoprotective Effects of Traditional Chinese Medicine on Liver Fibrosis from Ethanol Administration following Partial Hepatectomy.
abstract: The aim of this study was to establish the effective hepatoprotective properties of traditional Chinese medicines (TCMs) in fibrotic rat liver regeneration after partial hepatectomy (PHx). Fibrosis was induced in rats by ethanol (EtOH, 5 ml/kg) administration for 6, 24, 72, and 168 h. The rats were then fed four TCMs (1 g/kg/day, Codonopsis pilosula (CP), Salvia miltorrhiza Bunge (SMB), Bupleurum kasi (BK), and Elephantopus scaber L (ESL)) to Spraque-Dawley rats for 6, 24, 72 and 168 h, respectively. Surgical 70% cirrhotic fibrosis PHx was then conducted at 6, 24, 72, and 168 h. The effects on liver regeneration were examined to estimate and measure hepatocyte growth factor (HGF), focal adhesion kinase (FAK), Cyclin D1, Cyclin E, and retinoblastoma protein (pRb) protein expression using Western blotting analysis. Cyclin D1, matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitors of metalloproteinase (TIMP)-1, TIMP-2 and TIMP-3 mRNA by Reverse transcription polymerase chain reaction (RT-PCR) were analyzed in cirrhotic fibrosis rats. Transforming growth factor-β1 (TGF-β1), Cyclin D1, Cyclin E, pRb and E2F mRNA expression levels were determined in fibrotic rats following PHx using RT-PCR. We found elevated glutamyl oxaloacetic transaminase (GOT), glutamyl pyrubic transaminase (GPT), alkaline phosphatase (ALP), gammaglutamyl transpeptidase (γ-GT), glutathione (GSH), nonprotein sulfhydryl (NPSH) and total bilirubin in serum after 6 h EtOH administration. These levels were progressively decreased over 168 h. Total protein and albumin were reduced in serum after 6 h administration and then progressively increased. In contrast, tissues disorder histology and morphology were determined in liver sections. After rats were fed TCMs we found that SMB extraction not only induced HGF, FAK, Cyclin D1, and pRb protein expression and Cyclin D1 mRNA increases, but also reduced MMP-2 and MMP-9 after 24 and 72 h post injury. In the cell cycle S phase the Cyclin E protein expression was increased by ESL. CP induced TIMP-1, TIMP-2 and TIMP-3 mRNA increases in fibrotic rats. We detected liver regeneration in fibrotic rats. We also found that the liver regeneration index increased from 6 to 168 h post PHx. After 168 h fibrotic liver regeneration rats exhibited reduced TGF-β1 mRNA expression and enhanced Cyclin D1, Cyclin E, pRb and E2F mRNA expression. TCMs play a crucial role in the early mediating process in fibrotic rat liver regeneration after PHx.
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung 40402, Taiwan, Republic of China.
authors.forename: Jia-Ping
authors.initials: JP
authors.lastname: Wu
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan, Republic of China.|Chinese Medicine Department, China Medical University Beigang Hospital, Beigang, Yunlin 65152, Taiwan, Republic of China.
authors.forename: Tsung-Jung
authors.initials: TJ
authors.lastname: Ho
authors.affiliation: School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung 84001, Taiwan, Republic of China.|Chinese Medicine Department, E-Da Hospital, Kaohsiung 82445, Taiwan, Republic of China.
authors.forename: Chin-Chuan
authors.initials: CC
authors.lastname: Tsai
authors.affiliation: Department of pathology, Changhua Christian Hospital, Changhua 50006, Taiwan, Republic of China.|Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli 35664, Taiwan, Republic of China.
authors.forename: Yu-Lan
authors.initials: YL
authors.lastname: Yeh
authors.affiliation: Orthopaedic Department, Armed Forces General Hospital, Taichung 32551, Taiwan, Republic of China.
authors.forename: Chien-Chung
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Emergency Department, China Medical University Hospital, Taichung 40447, Taiwan, Republic of China.
authors.forename: Kuan-Ho
authors.initials: KH
authors.lastname: Lin
authors.affiliation: School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 40201, Taiwan, Republic of China.|Department of Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 40201, Taiwan, Republic of China.
authors.forename: Dennis Jine-Yuan
authors.initials: DJ
authors.lastname: Hsieh
authors.affiliation: Center of General Education, Central Taiwan University of Science & Technology, Taichung 40601, Taiwan, Republic of China.
authors.forename: Li-Mien
authors.initials: LM
authors.lastname: Chen
authors.affiliation: Department of Medical Imaging and Radiological Sciences of Central Taiwan University of Science and Technology, Taichung 40601, Taiwan, Republic of China.
authors.forename: Lung-Fa
authors.initials: LF
authors.lastname: Pan
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung 40402, Taiwan, Republic of China.|School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan, Republic of China.|Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan, Republic of China.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics; D000431:Ethanol / Q000633:toxicity*; D006498:Hepatectomy; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D008516:Medicine, Chinese Traditional; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000235:genetics
chemical_list: D016207:Cytokines; D053773:Transforming Growth Factor beta1; D000431:Ethanol