期刊论文详细信息
Lipids in Health and Disease
Fuzheng Huayu recipe prevents nutritional fibrosing steatohepatitis in mice
Jun Yu2  Yue-Min Nan1  Wen-Juan Wu1  Yu-Guo Zhang1  Su-Xian Zhao1  Wen-Cong Li1  Wei-Guang Ren1  Ling-Bo Kong1  Hong-Mei Mi1  Rong-Qi Wang1  Yan-Hong Jia1 
[1] Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China;Institute of Digestive Disease and Department of Medicine and Therapeutics, Li KaShing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
关键词: Oxidative stress;    Hepatic fibrosis;    Non-alcoholic steatohepatitis;    Chinese herb;    FuzhengHuayu;   
Others  :  1160320
DOI  :  10.1186/1476-511X-11-45
 received in 2012-02-24, accepted in 2012-03-28,  发布年份 2012
PDF
【 摘 要 】

Background

Fuzheng Huayu recipe (FZHY), a compound of Chinese herbal medicine, was reported to improve liver function and fibrosis in patients with hepatitis B virus infection. However, its effect on nutritional fibrosing steatohepatitis is unclear. We aimed to elucidate the role and molecular mechanism of FZHY on this disorder in mice.

Methods

C57BL/6 J mice were fed with methionine-choline deficient (MCD) diet for 8 weeks to induce fibrosing steatohepatitis. FZHY and/or heme oxygenase-1 (HO-1) chemical inducer (hemin) were administered to mice, respectively. The effect of FZHY was assessed by comparing the severity of hepatic injury, levels of hepatic lipid peroxides, activation of hepatic stellate cells (HSCs) and the expression of oxidative stress, inflammatory and fibrogenic related genes.

Results

Mice fed with MCD diet for 8 weeks showed severe hepatic injury including hepatic steatosis, necro-inflammation and fibrosis. Administration of FZHY or hemin significantly lowered serum levels of alanine aminotransferase, aspartate aminotransferase, reduced hepatic oxidative stress and ameliorated hepatic inflammation and fibrosis. An additive effect was observed in mice fed MCD supplemented with FZHY or/and hemin. These effects were associated with down-regulation of pro-oxidative stress gene cytochrome P450 2E1, up-regulation of anti-oxidative gene HO-1; suppression of pro-inflammation genes tumor necrosis factor alpha and interleukin-6; and inhibition of pro-fibrotic genes including α-smooth muscle actin, transforming growth factor beta 1, collagen type I (Col-1) and Col-3.

Conclusions

Our study demonstrated the protective role of FZHY in ameliorating nutritional fibrosing steatohepatitis. The effect was mediated through regulating key genes related to oxidative stress, inflammation and fibrogenesis.

【 授权许可】

   
2012 Jia et al; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150410101904628.pdf 2098KB PDF download
Figure 6. 60KB Image download
Figure 5. 61KB Image download
Figure 4. 49KB Image download
Figure 3. 62KB Image download
Figure 2. 101KB Image download
Figure 1. 78KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

【 参考文献 】
  • [1]Anstee QM, Daly AK, Day CP: Genetic modifiers of non-alcoholic fatty liver disease progression. Biochim Biophys Acta 2011, 812:1557-1566.
  • [2]Liu C, Hu Y, Xu L, Liu C, Liu P: Effect of Fuzheng Huayu formula and its actions against liver fibrosis. Chin Med 2009, 4:12. BioMed Central Full Text
  • [3]Zhao CQ, Wu YQ, Xu LM: Curative effects of Fuzheng Huayu capsules on hepatic fibrosis and the functional mechanisms. J Chin Integr Med 2006, 4:467-472.
  • [4]Liu P, Hu YY, Liu C, Xu LM, Liu CH, Sun KW, Hu DC, Yin YK, Zhou XQ, Wan MB, Cai X, Zhang ZQ, Ye J, Zhou RX, He J, Tang BZ: Multicenter clinical study on Fuzheng huayu capsule against liver fibrosis due to chronic hepatitis B. World J Gastroenterol 2005, 11:2892-2899.
  • [5]Nan YM, Han F, Kong LB, Zhao SX, Wang RQ, Wu WJ, Yu J: Adenovirus-mediated peroxisome proliferator activated receptor gamma overexpression prevents nutritional fibrotic steatohepatitis in mice. Scand J Gastroenterol 2011, 46:358-369.
  • [6]The Chinese National Workshop on Fatty Liver and Alcoholic Liver Disease for the Chinese Liver Disease Association: Guidelines for management of nonalcoholic fatty liver diseases: an updated and revised edition. Zhonghua Ganzangbing Zazhi 2010, 18:163-166.
  • [7]Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR: Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 1999, 94:2467-2474.
  • [8]Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ: Nonalcoholic Steatohepatitis clinical research network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005, 41:1313-1321.
  • [9]Yu J, Ip E, Dela Peña A, Hou JY, Sesha J, Pera N, Hall P, Kirsch R, Leclercq I, Farrell GC: COX-2 induction in mice with experimental nutritional steatohepatitis: role as pro-inflammatory mediator. Hepatology 2006, 43:826-836.
  • [10]Larter C, Yeh M: Animal models of NASH: getting both pathology and metabolic context right. J GastroenterolHepatol 2008, 23:1635-1648.
  • [11]Day CP, James OF: Hepatic steatosis: innocent bystander or guilty party? Hepatology 1998, 27:1463-1466.
  • [12]García-Galiano D, Sánchez-Garrido MA, Espejo I, Montero JL, Costán G, Marchal T, Membrives A, Gallardo-Valverde JM, Muñoz-Castañeda JR, Arévalo E, De la Mata M, Muntané J: IL-6 and IGF-1 are independent prognostic factors of liver steatosis and non-alcoholic steatohepatitis in morbidly obese patients. ObesSurg 2007, 17:493-503.
  • [13]Mantena SK, King AL, Andringa KK, Eccleston HB, Bailey SM: Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol- and obesity-induced fatty liver diseases. Free RadicBiol Med 2008, 44:1259-1272.
  • [14]Shen XD, Ke B, Zhai Y, Gao F, Busuttil RW, Cheng G, Kupiec-Weglinski JW: Toll-like receptor and heme oxygenase-1 signaling in hepatic ischemia/reperfusion injury. Am J Transplant 2005, 5:1793-1800.
  • [15]Farombi EO, Surh YJ: Heme-oxygenase-1 as a potential therapeutic target for hepatoprotection. J BiochemMolBiol 2006, 39:479-491.
  • [16]Camara NO, Soares MP: Heme oxygenase-1 (HO-1), a protective gene that prevents chronic graft dysfunction. Free RadicBiol Med 2005, 38:426-435.
  • [17]Tsuchihashi S, Zhai Y, Bo Q, Busuttil RW, Kupiec-Weglinski JW: Heme oxygenase-1 mediated cytoprotection against liver ischemia and reperfusion injury: inhibition of type-1 interferon signaling. Transplantation 2007, 83:1628-1634.
  • [18]Lickteig AJ, Fisher CD, Augustine LM, Cherrington NJ: Genes of the antioxidant response undergo upregulation in a rodent model of nonalcoholic steatohepatitis. J Biochem Mol Toxicol 2007, 21:216-220.
  • [19]Wang RQ, Nan YM, Wu WJ, Kong LB, Han F, Zhao SX, Kong L, Yu J: Induction of heme oxygenase-1 protects against nutritional fibrosing steatohepatitis in mice. Lipids Health Dis 2011, 10:31-41. BioMed Central Full Text
  • [20]Zhou T, Yan XC, Chen Q, Tao YY, Hu YY, Liu P, Liu CH: Effects of Chinese herbal medicine Fuzheng Huayu recipe and its components against hepatocyte apoptosis in mice with hepatic injury. Zhong Xi Yi Jie He XueBao 2011, 9:57-63.
  • [21]Jia W, Gao WY, Yan YQ, Wang J, Xu ZH, Zheng WJ, Xiao PG: The rediscovery of ancient Chinese herbal formulas. Phytother Res 2004, 18:681-686.
  • [22]Rombouts K, Marra F: Molecular mechanisms of hepatic fibrosis in non-alcoholic steatohepatitis. Dig Dis 2010, 28:229-235.
  • [23]Harmon RC, Tiniakos DG, Argo CK: Inflammation in nonalcoholic steatohepatitis. Expert Rev GastroenterolHepatol 2011, 5:189-200.
  • [24]Rose-John S, Mitsuyama K, Matsumoto S, Thaiss WM, Scheller J: Interleukin-6 trans-signaling and colonic cancer associated with inflammatory bowel disease. Curr Pharm Des 2009, 15:2095-2103.
  • [25]Nieto N: Oxidative-stress and IL-6 mediate the fibrogenic effects of rodent Kupffer cells on stellate cells. Hepatology 2006, 44:1487-1501.
  • [26]Di Sario A, Candelaresi C, Omenetti A, Benedetti A: Vitamin E in chronic liver diseases and liver fibrosis. Vitam Horm 2007, 76:551-573.
  • [27]Estep JM, Baranova A, Hossain N, Elariny H, Ankrah K, Afendy A, Chandhoke V, Younossi ZM: Expression of cytokine signaling genes inmorbidly obese patients with non-alcoholic steatohepatitis and hepatic fibrosis. Obes Surg 2009, 19:617-624.
  • [28]Friedman SL: Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiol Rev 2008, 88:125-172.
  • [29]Parola M, Marra F, Pinzani M: Myofibroblast-like cells and liver fibrogenesis: emerging concepts in a rapidly moving scenario. Mol Aspects Med 2008, 29:58-66.
  • [30]Jarcuska P, Janicko M, Veselíny E, Jarcuska P, Skladaný L: Circulating markers of liver fibrosis progression. Clin Chim Acta 2010, 411:1009-1017.
  • [31]Liu C, Wang X, Liu P: Serapharmacologicaleffect of Fuzheng Huayu 319 decoction on expression of type I collagen and transforming growth factor-β-1 in hepatic stellate cells. Zhongguo Zhong Xi Yi Jie He Za Zhi 1999, 19:412-414.
  • [32]Liu CH, Xuan HP, Tao YY, Hu YY: Mechanism of "Fuzheng Huayu recipe" against hepatic stellate cell activation through FN/Integrin signaling. Shang Hai Zhong Yi Yao Za Zhi 2008, 42:3-7.
  • [33]Yuan JL, Zhang Y, Jiang ZH: Effects of fuzheng huayu recipe in antagonizing rat's renal interstitial fibrosis. Zhongguo Zhong Xi Yi Jie He Za Zhi 2010, 30:76-79.
  • [34]Hellerbrand C, Stefanovic B, Giordano F, Burchardt ER, Brenner DA: The role of TGF beta1 in initiating hepatic stellate cell activation in vivo. J Hepatol 1999, 30:77-87.
  • [35]Shek FW, Benyon RC: How can transforming growth factor beta be targeted usefully to combat liver fibrosis? Eur J Gastroenterol Hepatol 2004, 16:123-126.
  • [36]de Gouville AC, Boullay V, Krysa G, Pilot J, Brusq JM, Loriolle F, Gauthier JM, Papworth SA, Laroze A, Gellibert F, Huet S: Inhibition of TGF-beta signaling by an ALK5 inhibitor protects rats from dimethylnitrosamine-induced liver fibrosis. Br J Pharmacol 2005, 145:166-177.
  • [37]Okuno M, Akita K, Moriwaki H, Kawada N, Ikeda K, Kaneda K, Suzuki Y, Kojima S: Prevention of rat hepatic fibrosis by the protease inhibitor, camostatmesilate, via reduced generation of active TGF-beta. Gastroenterology 2001, 120:1784-1800.
  • [38]Kim KH, Kim HC, Hwang MY, Oh HK, Lee TS, Chang YC, Song HJ, Won NH, Park KK: The antifibrotic effect of TGF-beta1 siRNAs in murine model of liver cirrhosis. Biochem Biophys Res Commun 2006, 343:1072-1078.
  • [39]Cheng K, Yang N, Ram I, Mahato RI: TGF-β1 Gene Silencing for Treating Liver Fibrosis. Mol Pharm 2009, 6:772-779.
  • [40]Jiang ZH, Cui HY, Liu CH, Liu C, Liu P, Xu LM, Hu YY, Yuan JL, Li FH: Effects of Fuzheng Huayu recipe on renal toxic interstitial fibrosis in rats. Zhong Xi Yi Jie He Xue Bao 2004, 2:358-360.
  • [41]Xuan HP, Sun BM, Tao YY, Hu YY, Liu CH: Effects of Fuzheng Huayu Decoction on steatohepatitis and liver fibrosis in rats. Yaopin Pingjia 2007, 4:414-418.
  文献评价指标  
  下载次数:17次 浏览次数:2次