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Journal of Chinese Integrative Medicine ›› 2012, Vol. 10 ›› Issue (12): 1405-1412.doi: 10.3736/jcim20121212

• Original Experimental Research • Previous Articles     Next Articles

Formula-syndrome correlation study of three classical anti-jaundice formulas in inhibition of liver fibrosis induced by dimethylnitrosamine in rats

Yan-qin Bian1,2, Bing-bing Ning1,2, Hong-yan Cao1,2, Yan Lu1,2, Cheng Liu1, Gao-feng Chen1,2, Jia Liu1,3, Ping Liu1,2,3(), Ming-yu Sun1,2,3()   

  1. 1. Institute of Liver Disease, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
    2. Key Laboratory of Liver and Kidney Diseases (Ministry of Education) , Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
    3. E-institute of Shanghai Municipal Education Commission, Shanghai 201203, China
  • Received:2012-07-24 Accepted:2012-08-08 Online:2012-12-20 Published:2018-12-15

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Objective: To investigate the effects of three classical anti-jaundice formulas Yinchenhao Decoction (YCHD), Yinchen Wuling San (YCWLS) and Zhizi Baipi Decoction (ZZBPD) on liver fibrosis induced by dimethylnitrosamine (DMN) in rats and explore the formula-syndrome relationship.
Methods: Forty-eight rats were weighted, and divided into five groups: normal control, DMN, YCHD, YCWLS and ZZBPD groups using stratified random method. Liver fibrosis in rats was induced by intraperitoneal injection of DMN for 4 weeks at the dosage of 10 mg/kg body weight, once per day for 3 consecutive days in each week. Each group was gavaged with distilled water (control or model group), YCHD, YCWLS and ZZBPD respectively in the last 2-week modeling period. At the end of the 4th week, rats were sacrificed and their blood sample and liver tissue were taken for detecting pathology and analyzing of hydroxyproline (Hyp) and liver function.
Results: Compared with the normal control group, DMN model group showed liver damage and liver fibrosis, with remarkably increased Hyp content (P<0.01) and abnormal liver function (P<0.01). Liver fibrosis induced by DMN in rats was improved by administration of YCHD. Compared with DMN model group, content of Hyp was decreased remarkably (P<0.01) and liver function and hepatic histology were improved significantly after 2 weeks of YCHD treatment (P<0.05 or P<0.01), while these effects were not shown in the YCWLS and ZZBPD groups. Comparison of various parameters between groups showed that content of serum total bilirubin was decreased significantly in the YCWLS group (P<0.01), and content of hepatic Hyp was decreased in the ZZBPD group.
Conclusion: Efficacy of YCHD in inhibition of liver fibrosis induced by DMN in rats is far better than YCWLS and ZZBPD. The pathogenesis of the liver fibrosis induced by DMN is mainly damp-heat. In addition, both damp and heat pathogenic factors play very important role in this model. The syndrome is highly correlated with the prescription YCHD.

Key words: liver cirrhosis,experimental, dimethylnitrosamine, compounds (TCD), rats

Table 1

Effects of three anti-jaundice formulas on body weight, liver weight, spleen weight, ratio of liver to body weight and ratio of spleen to body weight in rats with fibrosis liver (x±s)"

Group n Body weight (g) Liver weight (g) Spleen weight (g) Liver weight/
body weight (%)		 Spleen weight/
body weight (%)
A 10 318.70±25.95** 11.75±2.55** 0.66±0.07** 3.67±0.64** 0.21±0.017**
B 10 229.78±17.35 6.38±1.80 1.64±0.33 2.65±0.79 0.68±0.134
C 12 229.50±24.06 8.15±2.21* 1.61±0.18 3.54±0.69** 0.76±0.079
D 8 250.29±19.95*△ 7.47±1.62 1.61±0.17 2.85±0.61△ 0.59±0.059*△△
E 8 230.00±14.60 6.60±2.07 1.28±0.21**△△ 2.86±0.86△ 0.56±0.080**△△

Figure 1

Pathological changes in liver tissue observed by hematein and eosin staining (Light microscopy, ×200) A: Normal control group; B: Model group; C: Yinchenhao Decoction group; D: Yinchen Wuling San group; E: Zhizi Baipi Decoction group."

Figure 2

Collagen deposition in liver tissue observed by Sirius red staining (Light microscopy, ×100) A: Normal control group; B: Model group; C: Yinchenhao Decoction group; D: Yinchen Wuling San group; E: Zhizi Baipi Decoction group."

Figure 3

Effects of three anti-jaundice formulas on liver function in rats with dimethylnitrosamine-induced fibrosis *P<0.05, **P<0.01, vs B; △P<0.05, △△P<0.01, vs C. A: Normal control group; B: Model group; C: Yinchenhao Decoction group; D: Yinchen Wuling San group; E: Zhizi Baipi Decoction group. ALT: alanine aminotransferase; AST: aspartate aminotransferase; TBil: total bilirubin; ALB: albumin; GGT: gamma-glutamyl transpeptidase."

Table 2

Effects of three anti-jaundice formulas on liver Hyp content and collagen deposition in rats with dimethylnitrosamine-induced fibrosis"

Group n Hyp (x±s, μg/g fresh liver tissue) Collagen staging (n) Ridit
0 Ⅰ Ⅱ Ⅲ Ⅳ
A 10 139.82±27.11** 10 0 0 0 0 0.056±0.000**
B 10 531.30±122.57 0 0 3 2 5 0.712±0.287
C 12 394.74±72.03** 0 0 8 4 0 0.449±0.191**
D 8 450.40±93.34 0 0 3 4 1 0.593±0.240
E 8 424.32±82.11* 0 0 5 3 0 0.466±0.201*
[1] Xie M .Logic and significance of the correlation between syndrome and Chinese formulas. Beijing Zhong Yi Yao Da Xue Xue Bao. 2003; 26(2) : 11-12. Chinese.
doi: 10.3321/j.issn:1006-2157.2003.02.004
谢鸣 . 方证相关”逻辑命题及其意义. 北京中医药大学学报. 2003; 26(2) : 11-12.
doi: 10.3321/j.issn:1006-2157.2003.02.004
[2] Sun MY, Xie M . Research idea of syndrome and Chinese formulae. Zhongguo Yi Yao Xue Bao. 2002 ; 17(4):196-198. Chinese.
doi: 10.3969/j.issn.1673-1727.2002.04.001
孙明瑜, 谢鸣 . 试论证候与复方的研究思路.中国医药学报. 2002; 17(4):196-198.
doi: 10.3969/j.issn.1673-1727.2002.04.001
[3] Wang L, Liu P, Mu YP, Li FH, Long AH, Gu HT, Chen GF . Study on TCM recipe and syndrome of dime- thylnitrosamine-induced hepatic fibrosis in rats. Zhong Yi Za Zhi. 2006; 47(12) : 929-932. Chinese with abstract inEnglish.
doi: 10.3321/j.issn:1001-1668.2006.12.025
王磊, 刘平, 慕永平, 李凤华, 龙爱华, 顾宏图, 陈高峰 . 二甲基亚硝胺大鼠肝纤维化中医方证研究.中医杂志. 2006; 47(12) : 929-932.
doi: 10.3321/j.issn:1001-1668.2006.12.025
[4] Xu SY, Bian RL, Chen X. Experimental methodology of pharmacology. 3rd ed. Beijing: People’s Medical Publishing House. 2005. Chinese.
徐叔云, 卞如濂, 陈修 . 药理实验方法学.第3版.北京: 人民卫生出版社. 2005.
[5] Ala-Kokko L, Pihlajaniemi T, Myers JC, Kivirikko KI, Savolainen ER . Gene expression of type I, IE and ]Y collagens in hepatic fibrosis induced by dimethylnitrosamine in the rat. Biochem J. 1987; 244(1):75-79.
doi: 10.1042/bj2440075
[6] Jamall IS, Finelli VN, Que Hee SS . A simple method to determine nanogram levels of 4-hydroxyproline in biological tissues. Anal Biochem. 1981; 112(1) : 70-75.
doi: 10.1016/0003-2697(81)90261-X pmid: 7258630
[7] Scheuer PJ . Classification of chronic viral hepatitis: a need for reassessment.J Hepatol. 1991 ; 13(3) : 372-374.
[8] Jézéquel AM, Mancini R, Rinaldesi ML, Macarri G, Venturini C, Orlandi F . A morphological study of the early stages of hepatic fibrosis induced by low doses of dimethylnitrosamine in the rat.J Hepatol. 1987 ; 5(2):174-181 .
[9] Hong M, Dong ZB, Sun XY, Li XD, Zhu Q . Protective effect of Yinchenhao Decoction on ethanol-induced liver injury in rats. Nanjing Zhong Yi Yao Da Xue Xue Bao. 2004; 20(5) : 303-304. Chinese.
洪敏, 董自波, 孙小玉, 李晓冬, 朱荃 . 茵陈蒿汤对大鼠酒精性肝损伤的保护作用.南京中医药大学学报. 2004; 20(5) : 303-304.
[10] Liu C, Sun M, Wang L, Wang G, Chen G, Liu C, Liu P . Effects of Yinchenhao Tang and related decoctions on DMN-induced cirrhosis/fibrosis in rats. Chin Med. 2008; 3:1.
doi: 10.1186/1749-8546-3-1 pmid: 18237412
[11] Imanishi Y, Maeda N, Otogawa K, Seki S, Matsui H, Kawada N, Arakawa T . Herb medicine Inchin-ko-to (TJ-135) regulates PDGF-BB-dependent signaling pathways of hepatic stellate cells in primary culture and attenuates development of liver fibrosis induced by thioacetamide administration in rats. J Hepatol. 2004; 41(2):242-250.
doi: 10.1016/j.jhep.2004.04.005
[12] Liu C, Sun M, Yan X, Han L, Zhang Y, Liu C, El- Nezami H, Liu P . Inhibition of hepatic stellate cell activation following Yinchenhao decoction administration to dime- thylnitrosamine-treated rats. Hepatol Res. 2008; 38(9):919-929.
doi: 10.1111/hep.2008.38.issue-9
[13] Hong M, Zhu Q, Sun XY . Anti-hepatotoxic mechanism of alcohol extract of capillaris decoction — effect on LPS induced release of TNF from mouse peritoneal macrophage in vitro. Zhong Yao Yao Li Yu Lin Chuang. 1999 ; 15(1):3-6. Chinese with abstract inEnglish.
doi: 10.3969/j.issn.1001-859X.1999.03.003
洪敏, 朱荃, 孙小玉 . 茵陈蒿汤保肝作用的机理——对小鼠腹腔巨噬细胞释放TNF的影响.中药药理与临床. 1999; 15(1):3-6.
doi: 10.3969/j.issn.1001-859X.1999.03.003
[14] Liu C, Liu P, Tao Q, Sun MY, Chen GF, Wang GQ, Wang L, Du JX, Tong X, Du GL, Mu YP, Liu CH, Hu YY. Recipe-syndrome correlation and pathogenesis mechanism of Yinchenhao Decoction in intervening dimethylnitrosamine-induced liver cirrhosis progress in rats. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2010 ; 30(8):845-850. Chinese with abstract inEnglish.
刘成, 刘平, 陶庆, 孙明瑜, 陈高峰, 王高强, 王磊, 都金星, 仝欣, 都广礼, 慕永平, 刘成海, 胡义扬 . 茵陈蒿汤干预二甲基亚硝胺大鼠肝硬化效应的方证病理学基础研究.中国中西医结合杂志. 2010; 30(8):845-850.
[15] Zhu PS, Wang B, Long AH . Effect of different classic formulas on the liver and renal function of extrahepatic cholestasis in rats. Zhong Yi Za Zhi. 2011; 52(4):319-321, 348. Chinese with abstract inEnglish.
朱平生, 王兵, 龙爱华 . 不同经典方剂对肝外胆汁淤积大鼠肝肾功能的影响.中医杂志. 2011; 52(4):319-321, 348.
[16] Sun YN, Feng J . Advancement of the study on the chemical composition and pharmacological activities of Yinchenhao Decoction. Zhongguo Xian Dai Yi Sheng. 2011; 49(21):12-14. Chinese.
孙远南, 冯健 . 茵陈蒿汤的化学成分与药理作用研究进展.中国现代医生. 2011; 49(21):12-14.
[17] Meng XL, Li HW, Li Y, Yu Q, Wang LL, Guo C . Advances in studies on chemical constituents and pharmacological activities of Gardenia jasminoides. Zhongguo Xin Yao Za Zhi. 2011; 20(11):959-967. Chinese with abstract inEnglish.
孟祥乐, 李红伟, 李颜, 余奇, 万丽丽, 郭澄 . 梔子化学成分及其药理作用研究进展.中国新药杂志. 2011; 20(11):959-967.
[18] Zhou F, Xu HM . Effect of eomdin on P-gp expression in intrahepatic cholestatic rats. Zhongguo Zhong Yao Za Zhi. 2010; 35(7):908-911. Chinese with abstract inEnglish.
doi: 10.4268/cjcmm20100724
周方, 许红梅 . 大黄素对肝内胆汁淤积大鼠P-gp表达的影响.中国中药杂志. 2010; 35(7):908-911.
doi: 10.4268/cjcmm20100724
[19] Luo YL, Zeng JW, Yu M, Wei YL, Qu SY, Li W, Zheng TZ . Effect of rhubarb on contractile response of gallbladder smooth muscle strips isolated from guinea pigs. World J Gastroenterol. 2005; 11(6):863-866.
[20] Xu X, Li BP, Zhang HF . Advancement of the study on rhubarb. Shanghai Zhong Yi Yao Za Zhi. 2003 ; 37(4) : 56-59. Chinese with abstract inEnglish.
徐翔, 郦柏平, 张慧芬 . 大黄的研究进展.上海中医药杂志. 2003; 37(4) : 56-59.
[21] Chen Y, Zhao H, Xie R . Review of pharmacology and clinical research on rhubarb. Xi Nan Guo Fang Yi Yao. 2005; 15(2):178-180. Chinese.
doi: 10.3969/j.issn.1004-0188.2005.02.028
陈燕, 赵辉, 谢锐 . 大黄的药理及临床研究近况.西南国防医药. 2005; 15(2):178-180.
doi: 10.3969/j.issn.1004-0188.2005.02.028
[22] Jin H, Sakaida I, Tsuchiya M, Okita K . Herbal medicine Rhei rhizome prevents liver fibrosis in rat liver cirrhosis induced by a choline-deficient L-amino acid-defined diet. LifeSci. 2005; 76(24):2805-2816.
doi: 10.1016/j.lfs.2004.09.041
[23] Lin YL, Wu CF, Huang YT . Effects of rhubarb on migration of rat hepatic stellate cells.[J] Gastroenterol Hepatol. 2009; 24(3):453-461.
doi: 10.1111/j.1440-1746.2008.05573.x pmid: 19175832
[24] Zhu HF, Zhu TX, Zhu DX . The dual regulation of Wuling San. Shizhen Guo Yi Guo Yao. 1998; 9(6) : 542. Chinese.
朱海峰, 朱同宣, 朱冬霞 . 五苓散的双向调节作用.时珍国医国药. 1998; 9(6) : 542.
[25] Wu JR, Zhang B, Zhang GM . Research advance on pharmacological actions of Cortex Phellodendri . Ya Tai Chuan Tong Yi Yao. 2009; 5(11):160-162. Chinese.
吴嘉瑞, 张冰, 张光敏 . 黄柏药理作用研究进展.亚太传统医药. 2009; 5(11):160-162.
[26] Gao XY, Wang WQ, Wei SL, Li WD . Review of pharmacological effects of Glycyrrhiza radix and its bioactive compounds. Zhongguo Zhong Yao Za Zhi. 2009 ; 34(21):2695-2700. Chinese with abstract inEnglish.
高雪岩, 王文全, 魏胜利, 李卫东 . 甘草及其活性成分的药理活性研究进展.中国中药杂志. 2009; 34(21):2695-2700.
[27] Liu Y, Xie M . Thinking about the method of presumption of syndrome based on Chinese prescription. Zhong Yi Za Zhi. 2007; 48(5) : 459-461. Chinese.
刘玥, 谢鸣 . 关于“以方测证”方法的思考.中医杂志. 2007; 48(5) : 459-461.
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