Search JIM Advanced Search

Journal of Chinese Integrative Medicine ›› 2011, Vol. 9 ›› Issue (6): 651-657.doi: 10.3736/jcim20110612

• Original Experimental Research • Previous Articles     Next Articles

Effects of Chinese herbal medicine Yiguanjian Decoction on collagen metabolism of hepatic tissues in rats with CCI4-induced liver fibrosis

Xiao-ning Wang, Qing Tao, Qin Feng, Jing-hua Peng, Ping Liu, Yi-yang Hu()   

  1. Institute of Liver Diseases, Shuguang Hospital, E-institute of Traditional Chinese Internal Medicine of Shanghai Municipal Education Commission, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
  • Received:2011-03-25 Accepted:2011-04-11 Online:2011-06-20 Published:2011-06-15
  • Contact: Hu Yi-yang E-mail:yyhuliver@163.com

Objective: To investigate the effects of Yiguanjian Decoction, a compound traditional Chinese herbal medicine, on collagen metabolism of hepatic tissues in rats with carbon tetrachloride (CCl4)-induced liver fibrosis.
Methods: Liver fibrosis was induced in rats by intraperitoneal injection of 50% CCl4-olive oil solution at a dose of 1 mL/kg body weight, twice per week for 9 consecutive weeks. Six rats were sacrificed for dynamic observation at the end of the 3rd and 6th week respectively, and the other rats were divided into 9-week untreated group and Yiguanjian Decoction group which was given Yiguanjian Decoction intragastrically in the subsequent 3-week modeling period. Another 6 rats were used as normal group. Rats in the normal group and 9-week untreated group were treated with distilled water. At the end of the 9th week, all rats were sacrificed, and their blood serum and liver tissue were collected for measuring hepatic histology and expressions of α-smooth muscle actin (α-SMA), tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, matrix metalloproteinase (MMP)-13, MMP-14, collagen type Ⅰ (ColⅠ), and activities of MMP-2 and -9.
Results: Compared with the normal group, collagen fiber deposition, expressions of α-SMA, ColⅠ, TIMP-1, TIMP-2, MMP-13 and MMP-14 and activities of MMP-2 and -9 in the liver tissues gradually increased in the untreated group (P<0.05, P<0.01). These changes were significantly suppressed by Yiguanjian Decoction.
Conclusion: Yiguanjian Decoction exerts inhibition on formation of CCl4-induced cirrhosis in rats. The therapeutic mechanism may be related to inhibiting hepatic stellate cell activation, collagen secretion, and promoting collagen fiber degradation.

Key words: liver fibrosis, hepatic stellate cell, collagen metabolism, Yiguanjian Decoction, rats

"

"

Figure 1

Expressions of α-SMA, TIMP-1, TIMP-2, MMP-13 and MMP-14 proteins in liver tissues of rats measured by Western blotting A: Expressions of α-SMA, TIMP-1, TIMP-2, MMP-13, MMP-14 and GAPDH proteins, which were consecutively blotted by incubation with different antibodies on the same membrane. 1: 9 week normal group; 2: 3 week untreated group; 3: 6 week untreated group; 4: 9 week untreated group; 5: Yiguanjian Decoction group. B, C, D, E,F: Semi-quantification results of α-SMA, TIMP-1, TIMP-2, MMP-13 and MMP-14 with GAPDH, represented as the mean±SD, n=3. ▲, P<0.05, ▲▲,P<0.01. MMP: matrix metalloproteinase; TIMP: tissue inhibitor of metalloproteinase; α-SMA: α-smooth muscle actin; GAPDH: glyceraldehyde-3-phosphate dehydrogenase."

Figure 2

Expression of collagen type Ⅰ in liver tissues of rats measured by immunofluorescent staining (Cy2, green) (Light microscopy, ×200) A: Normal group; B: 3 week untreated group; C: 6 week untreated group; D: 9 week untreated group; E: Yiguanjian Decoction group."

Figure 3

Changes of MMP-2 and MMP-9 activities in liver tissues of rats observed by Gelatin zymography A: Gelatin zymography of MMP-9 and MMP-2. 1: 9 week normal group; 2: 3 week untreated group; 3: 6 week untreated group; 4: 9 week untreated group; 5: Yiguanjian Decoction group. B, C: Semi-quantification results of MMP-9 and -2 activities, represented as the mean±SD, n=3. ▲, P<0.05, ▲▲, P<0.01. MMP: matrix metalloproteinase."

[1] Mu Y, Liu P, Du G, Du J, Wang G, Long A, Wang L, Li F . Action mechanism of Yi Guan Jian Decoction on CCl4 induced cirrhosis in rats[J]. J Ethnopharmacol, 2009,121(1):35-42
doi: 10.1016/j.jep.2008.09.032 pmid: 18996463
[2] Shen DZ, Tao Q, Du JX, Ding SD, Chen GF, Hu YY, Liu P . Effects of Yiguanjian Decoction on liver cirrhosis formation: a differential proteomics study in rats[J]. J Chin Integr Med, 2010,8(2):158-167
申定珠, 陶庆, 都金星, 丁赛丹, 陈高峰, 胡义扬, 刘平 . 基于差异蛋白质组学解析一贯煎对大鼠肝硬化形成的影响[J]. 中西医结合学报, 2010,8(2):158-167
[3] Nakamura T, Akiyoshi H, Saito I, Sato K . Adenovirus-mediated gene expression in the septal cells of cirrhotic rat livers[J]. J Hepatol, 1999,30(1):101-106
doi: 10.1016/S0168-8278(99)80013-0 pmid: 9927156
[4] Scheuer PJ . Classification of chronic viral hepatitis: a need for reassessment[J]. J Hepatol, 1991,13(3):372-374
doi: 10.1016/0168-8278(91)90084-O
[5] Kristensen DB, Kawada N, Imamura K, Miyamoto Y, Tateno C, Seki S, Kuroki T, Yoshizato K . Proteome analysis of rat hepatic stellate cells[J]. Hepatology, 2000,32(2):268-277
doi: 10.1053/jhep.2000.9322 pmid: 10915733
[6] Kleiner DE, Stetler-Stevenson WG . Quantitative zymography: detection of picogram quantities of gelatinases[J]. Anal Biochem, 1994,218(2):325-329
doi: 10.1006/abio.1994.1186 pmid: 8074288
[7] Benyon RC, Arthur MJ . Extracellular matrix degradation and the role of hepatic stellate cells[J]. Semin Liver Dis, 2001,21(3):373-384
doi: 10.1055/s-2001-17552
[8] Kawada N . Evolution of hepatic fibrosis research[J]. Hepatol Res, 2011,41(3):199-208
doi: 10.1111/j.1872-034X.2011.00776.x pmid: 21338451
[9] Hernandez-Gea V, Friedman SL . Pathogenesis of liver fibrosis[J]. Annu Rev Pathol, 2011,6:425-456
doi: 10.1146/annurev-pathol-011110-130246
[10] Friedman SL . Evolving challenges in hepatic fibrosis[J]. Nat Rev Gastroenterol Hepatol, 2010,7(8):425-436
doi: 10.1038/nrgastro.2010.97 pmid: 20585339
[11] Brenner DA . Molecular pathogenesis of liver fibrosis[J]. Trans Am Clin Climatol Assoc, 2009,120:361-368
pmid: 19768189
[12] Das SK, Vasudevan DM . Genesis of hepatic fibrosis and its biochemical markers[J]. Scand J Clin Lab Invest, 2008,68(4):260-269
doi: 10.1080/00365510701668516 pmid: 18609066
[13] Coussens LM, Fingleton B, Matrisian LM . Matrix metalloproteinase inhibitors and cancer: trials and tribulations[J]. Science, 2002,295(5564):2387-2392
doi: 10.1126/science.1067100
[14] Zhu SJ, Sun W, Xue WD . Research advances in changes of gene expression during liver fibrosis[J]. Jiangsu Da Xue Xue Bao Yi Xue Ban, 2010,20(1):86-90, 92
朱述钧, 孙文, 薛文达 . 肝纤维化过程中基因表达变化的研究进展[J]. 江苏大学学报:医学版, 2010,20(1):86-90, 92
[15] Takahara T, Furui K, Funaki J, Nakayama Y, Itoh H, Miyabayashi C, Sato H, Seiki M, Ooshima A, Watanabe A . Increased expression of matrix metalloproteinase-Ⅱ in experimental liver fibrosis in rats[J]. Hepatology, 1995,21(3):787-795
doi: 10.1002/hep.1840210328 pmid: 7875677
[16] Galli A, Svegliati-Baroni G, Ceni E, Milani S, Ridolfi F, Salzano R, Tarocchi M, Grappone C, Pellegrini G, Benedetti A, Surrenti C, Casini A . Oxidative stress stimulates proliferation and invasiveness of hepatic stellate cells via a MMP2-mediated mechanism[J]. Hepatology, 2005,41(5):1074-1084
doi: 10.1002/(ISSN)1527-3350
[17] Benyon RC, Iredale JP, Goddard S, Winwood PJ, Arthur MJ . Expression of tissue inhibitor of metalloproteinases 1 and 2 is increased in fibrotic human liver[J]. Gastroenterology, 1996,110(3):821-831
doi: 10.1053/gast.1996.v110.pm8608892
[18] Barascuk N, Veidal SS, Larsen L, Larsen DV, Larsen MR, Wang J, Zheng Q, Xing R, Cao Y, Rasmussen LM, Karsdal MA . A novel assay for extracellular matrix remodeling associated with liver fibrosis: An enzyme-linked immunosorbent assay(ELISA) for a MMP-9 proteolytically revealed neo-epitope of type Ⅲ collagen[J]. Clin Biochem, 2010,43(10-11):899-904
doi: 10.1016/j.clinbiochem.2010.03.012
[19] Arthur MJ, Mann DA, Iredale JP . Tissue inhibitors of metalloproteinases, hepatic stellate cells and liver fibrosis[J]. J Gastroenterol Hepatol, 1998,( 13 Suppl):S33-S38
doi: 10.1186/gb-2011-12-11-233 pmid: 9792032
[20] Adams LA, Angulo P . Role of liver biopsy and serum markers of liver fibrosis in non-alcoholic fatty liver disease[J]. Clin Liver Dis, 2007,11(1):25-35
doi: 10.1016/j.cld.2007.02.004 pmid: 17544970
[21] Hemmann S, Graf J, Roderfeld M, Roeb E . Expression of MMPs and TIMPs in liver fibrosis — a systematic review with special emphasis on anti-fibrotic strategies[J]. J Hepatol, 2007,46(5):955-975
doi: 10.1016/j.jhep.2007.02.003
[22] Iredale JP . Hepatic stellate cell behavior during resolution of liver injury[J]. Semin Liver Dis, 2001,21(3):427-436
doi: 10.1055/s-2001-17557 pmid: 11586470
[23] Trim JE, Samra SK, Arthur MJ, Wright MC, McAulay M, Beri R, Mann DA .Upstream tissue inhibitor of metalloproteinases-1(TIMP-1) element-1, a novel and essential regulatory DNA motif in the human TIMP-1 gene promoter, directly interacts with a 30-kDa nuclear protein[J]. J Biol Chem, 2000,275(9):6657-6663
doi: 10.1074/jbc.275.9.6657
[24] El-Gindy I, El Rahman AT, El-Alim MA, Zaki SS . Diagnostic potential of serum matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 as non-invasive markers of hepatic fibrosis in patients with HCV related chronic liver disease[J]. Egypt J Immunol, 2003,10(1):27-35
[25] Murawaki Y, Ikuta Y, Idobe Y, Kitamura Y, Kawasaki H . Tissue inhibitor of metalloproteinase-1 in the liver of patients with chronic liver disease[J]. J Hepatol, 1997,26(6):1213-1219
doi: 10.1016/S0168-8278(97)80454-0 pmid: 9210606
[26] Iredale JP, Benyon RC, Pickering J, McCullen M, Northrop M, Pawley S, Hovell C, Arthur MJ .Mechanisms of spontaneous resolution of rat liver fibrosis. Hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors[J]. J Clin Invest, 1998,102(3):538-549
doi: 10.1172/JCI1018
[27] Herbst H, Wege T, Milani S, Pellegrini G, Orzechowski HD, Bechstein WO, Neuhaus P, Gressner AM, Schuppan D . Tissue inhibitor of metalloproteinase-1 and -2 RNA expression in rat and human liver fibrosis[J]. Am J Pathol, 1997,150(5):1647-1659
[1] Morufu Eyitayo Balogun, Elizabeth Enohnyaket Besong, Jacinta Nkechi Obimma, Ogochukwu Sophia Mbamalu, Fankou Serges Athanase Djobissie. Protective roles of Vigna subterranea (Bambara nut) in rats with aspirin-induced gastric mucosal injury. Journal of Integrative Medicine, 2018, 16(5): 342-349.
[2] Lucky Legbosi Nwidu, Raphael Ellis Teme. Hot aqueous leaf extract of Lasianthera africana (Icacinaceae) attenuates rifampicin-isoniazid-induced hepatotoxicity. Journal of Integrative Medicine, 2018, 16(4): 263-272.
[3] Kylie Connolly, Douglas Jackson, Candice Pullen, Andrew Fenning. Alpha-adrenoceptor antagonism by Crassostrea gigas oyster extract inhibits noradrenaline-induced vascular contraction in Wistar rats. Journal of Integrative Medicine, 2015, 13(3): 194-200.
[4] Hussein O. B. Oloyede, Matthew C. Adaja, Taofeek O. Ajiboye, Musa O. Salawu. Anti-ulcerogenic activity of aqueous extract of Carica papaya seed on indomethacin-induced peptic ulcer in male albino rats. Journal of Integrative Medicine, 2015, 13(2): 105-114.
[5] Udhaya Lavinya Baskaran, Sherry Joseph Martin, Rasool Mahaboobkhan, Sabina Evan Prince. Protective role of Triphala, an Indian traditional herbal formulation, against the nephrotoxic effects of bromobenzene in Wistar albino rats. Journal of Integrative Medicine, 2015, 13(2): 115-121.
[6] Anirudha A. Lande, Shirishkumar D. Ambavade, Uma S. Swami, Prafulla P. Adkara Prashant D. Ambavade, Arun B. Waghamare. Saponins isolated from roots of Chlorophytum borivilianum reduce acute and chronic inflammation and histone deacetylase. Journal of Integrative Medicine, 2015, 13(1): 25-33.
[7] Elizabeth Abidemi Balogun, Sylvia Orume Malomo, Joseph Oluwatope Adebayo, Ahmed Adebayo Ishola, Ayodele Olufemi Soladoye, Lawrence Aderemi Olatunji, Olatunji Matthew Kolawole, Stephen Olubunmi Oguntoye, Abiola Samuel Babatunde, Oluwole Busayo Akinola . In vivo antimalarial activity and toxicological effects of methanolic extract of Cocos nucifera (Dwarf red variety) husk fibre. Journal of Integrative Medicine, 2014, 12(6): 504-511.
[8] Xin-fang Zhang, Ji Zhu, Wen-ye Geng, Shu-jun Zhao, Chuan-wei Jiang, Sheng-rong Cai, Miao Cheng, Chuan-yun Zhou, Zi-bing Liu. Electroacupuncture at Feishu (BL13) and Zusanli (ST36) down-regulates the expression of orexins and their receptors in rats with chronic obstructive pulmonary disease. Journal of Integrative Medicine, 2014, 12(5): 417-424.
[9] Urmila Aswar, Mayuri Gurav, Ganesh More, Khaled Rashed, Manoj Aswar. Effect of aqueous extract of Solanum xanthocarpum Schrad. & Wendl. on postmenopausal syndrome in ovariectomized rats. Journal of Integrative Medicine, 2014, 12(5): 439-446.
[10] Benjamin Perry, Junzeng Zhang, Tarek Saleh, Yanwen Wang. Liuwei Dihuang, a traditional Chinese herbal formula, suppresses chronic inflammation and oxidative stress in obese rats. Journal of Integrative Medicine, 2014, 12(5): 447-454.
[11] Upendarrao Golla, Praveen Kumar Gajam, Solomon Sunder Bhimathati. Evaluation of diuretic and laxative activity of hydro-alcoholic extract of Desmostachya bipinnata (L.) Stapf in rats. Journal of Integrative Medicine, 2014, 12(4): 372-378.
[12] Shu Dong, Shi-bing Su​. Advances in mesenchymal stem cells combined with traditional Chinese medicine therapy for liver fibrosis. Journal of Integrative Medicine, 2014, 12(3): 147-155.
[13] Qian Zhang, Xin-hua Xiao, Ming Li, Wen-hui Li, Miao Yu, Hua-bing Zhang, Fan Ping, Zhi-xin Wang, Jia Zheng ​. Chromium-containing traditional Chinese medicine, Tianmai Xiaoke Tablet improves blood glucose through activating insulin-signaling pathway and inhibiting PTP1B and PCK2 in diabetic rats. Journal of Integrative Medicine, 2014, 12(3): 162-170.
[14] Amir Rashidian​, Saeed Mehrzadi, Ali Reza Ghannadi, Parvin Mahzooni, Samira Sadr, Mohsen Minaiyan​. Protective effect of ginger volatile oil against acetic acid-induced colitis in rats: A light microscopic evaluation. Journal of Integrative Medicine, 2014, 12(2): 115-120.
[15] Dilpesh Jain​, Manish Kumar Bansal, Rahul Dalvi​, Aman Upganlawar​, Rahul Somani​. Protective effect of diosmin against diabetic neuropathy in experimental rats. Journal of Integrative Medicine, 2014, 12(1): 35-41.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] Li Zhou, Hong-xing Zhang, Ling-guang Liu, Wen-jun Wan. Effect of electro-acupuncture at Fenglong (GV 16) on nitric oxide and endothelin in rats with hyperlipidemia. Journal of Chinese Integrative Medicine, 2008, 6(1): 89-92
[2] Hong Liu , Guo-liang Zhang, Li Shen , Zhen Zeng, Bao-luo Zhou, Cheng-hai Liu, Guang Nie . Application and evaluation of a pseudotyped virus assay for screening herbs for anti-H5Nl avian influenza virus. Journal of Chinese Integrative Medicine, 2010, 8(11): 1036-1040
[3] Gui Yu, Jie Wang. Thinking on building the network cardiovasology of Chinese medicine. Journal of Chinese Integrative Medicine, 2012, 10(11): 1206-1210
[4] Ming-qing Wei , Jin-zhou Tian , Jing Shi , Fu-yun Ma , Ying-chun Miao , Yong-yan Wang. Effects of Chinese medicine for promoting blood circulation and removing blood stasis in treating patients with mild to moderate vascular dementia: a randomized, double-blind and parallel-controlled trial. Journal of Chinese Integrative Medicine, 2012, 10(11): 1240-1246
[5] Ying Xu , Chang-chun Zeng , Xiu-yu Cai , Rong-ping Guo , Guang Nie , Ying Jin. Chromaticity and optical spectrum colorimetry of the tongue color in different syndromes of primary hepatic carcinoma. Journal of Chinese Integrative Medicine, 2012, 10(11): 1263-1271
[6] Ji Chen, Qin Pan, Li-shuang Ye, Jia-ling Huang. English translation of cultural aspects of the titles of traditional Chinese medicine classics based on the skopos theory. Journal of Chinese Integrative Medicine, 2012, 10(11): 1316-1320
[7] Peng-fei Gao, Kenji Watanabe. Introduction of the World Health Organization project of the International Classification of Traditional Medicine. Journal of Chinese Integrative Medicine, 2011, 9(11): 1161-1164
[8] Yong Miao Edwin. Clinical critical qualitative evaluation of the selected randomized controlled trials in current acupuncture researches for low back pain. Journal of Chinese Integrative Medicine, 2010, 8(12): 1133-1146
[9] Kai Qu, Tian-fang Wang, Yan Zhao, Xiao-lin Xue, Xiu-yan Wu, Hua-liang Deng, Lu Yang, Li-liYu , Hong Yue, Qing-guo Wang. Common syndrome factors of traditional Chinese medicine in chronic renal failure based on the questionnaire investigation among experts. Journal of Chinese Integrative Medicine, 2010, 8(12): 1147-1152
[10] Mei-jun Lü, Hui-yong Zhang, Zhe Zhang, Guan-lin Yang. Measurement of health-related quality of life in coronary heart disease: A review. Journal of Chinese Integrative Medicine, 2011, 9(12): 1277-1285