BMC Complementary and Alternative Medicine | |
Protective effects of extracts from Pomegranate peels and seeds on liver fibrosis induced by carbon tetrachloride in rats | |
Wei-jin Zang3  Ming Zhao3  A-li Luo4  Guo-xia Ren4  Xue-yuan Bi3  Yong-hua Yang1  Ru-tang Fang2  Xiang-lan Wei4  | |
[1] Department of pediatrics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, People’s Republic of China;Department of Gastroenterology, The 451 Hospital of the Chinese People’s Liberation Army, Xi’an 710054, People’s Republic of China;Department of Pharmacology, Xi’an Jiaotong University Health Science Center, No.76 Yanta West Road, Xi’an 710061, People’s Republic of China;Department of Pharmacy, Xi’an Chest Hospital, Xi’an 710061, People’s Republic of China | |
关键词: Oxidative stress; Liver fibrosis; The extract of pomegranate seeds; The extract of pomegranate peels; | |
Others : 1233210 DOI : 10.1186/s12906-015-0916-9 |
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received in 2015-03-17, accepted in 2015-10-14, 发布年份 2015 | |
【 摘 要 】
Background
Liver fibrosis is a feature in the majority of chronic liver diseases and oxidative stress is considered to be its main pathogenic mechanism. Antioxidants including vitamin E, are effective in preventing liver fibrogenesis. Several plant-drived antioxidants, such as silymarin, baicalin, beicalein, quercetin, apigenin, were shown to interfere with liver fibrogenesis. The antioxidans above are polyphenols, flavonoids or structurally related compounds which are the main chemical components of Pomegranate peels and seeds, and the antioxidant activity of Pomegranate peels and seeds have been verified. Here we investigated whether the extracts of pomegranate peels (EPP) and seeds (EPS) have preventive efficacy on liver fibrosis induced by carbon tetrachloride (CCl 4 ) in rats and explored its possible mechanisms.
Methods
The animal model was established by injection with 50 % CCl 4subcutaneously in male wistar rats twice a week for four weeks. Meanwhile, EPP and EPS were administered orally every day for 4 weeks, respectively. The protective effects of EPP and EPS on biochemical metabolic parameters, liver function, oxidative markers, activities of antioxidant enzymes and liver fibrosis were determined in CCl 4 -induced liver toxicity in rats.
Results
Compared with the sham group, the liver function was worse in CCl 4group, manifested as increased levels of serum alanine aminotransferase, aspartate aminotransferase and total bilirubin. EPP and EPS treatment significantly ameliorated these effects of CCl 4 . EPP and EPS attenuated CCl 4 –induced increase in the levels of TGF-β1, hydroxyproline, hyaluronic acid laminin and procollagen type III. They also restored the decreased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and inhibited the formation of lipid peroxidized products in rats treated with CCl 4 .
Conclusion
The EPP and EPS have protective effects against liver fibrosis induced by CCl 4 , and its mechanisms might be associated with their antioxidant activity, the ability of decreasing the level of TGF-β1 and inhibition of collagen synthesis.
【 授权许可】
2015 Wei et al.
【 预 览 】
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【 参考文献 】
- [1]Sun WY, Wei W, Wu L, Gui SY, Wang H. Effects and mechanisms of extract from Paeonia lactiflora and Astragalus membranaceus on liver fibrosis induced by carbon tetrachloride in rats. J Ethnopharmacol. 2007; 112:514-523.
- [2]Huang X, Wang X, Lv Y, Xu L, Lin J, Diao Y. Protection effect of kallistatin on carbon tetrachloride-induced liver fibrosis in rats via antioxidative stress. Plos ONE. 2014; 9: Article ID e88498
- [3]Friedman SL. Liver fibrosis -- from bench to bedside. J Hepatol. 2003; 38 Suppl 1:S38-S53.
- [4]Kisseleva T, Brenner DA. Hepatic stellate cells and the reversal of fibrosis. J Gastroen Hepatol. 2006; 21:S84-S87.
- [5]Dai LJ, Li HY, Guan LX, Ritchie G, Zhou JX. The therapeutic potential of bone marrow-derived mesenchymal stem cells on hepatic cirrhosis. Stem Cell Res. 2009; 2:16-25.
- [6]Sun WY, Wang L, Liu H, Li X, Wei W. A standardized extract from Paeonia lactiflora and Astragalus membranaceus attenuates liver fibrosis induced by porcine serum in rats. Int J Mol Med. 2012; 29:491-498.
- [7]Cederbaum AI, Lu Y, Wu D. Role of oxidative stress in alcohol-induced liver injury. Arch Toxicol. 2009; 83:519-548.
- [8]Aboutwerat A, Pemberton PW, Smith A, Burrows PC, McMahon RF, Jain SK, Warnes TW. Oxidant stress is a significant feature of primary biliary cirrhosis. Biochim Biophys Acta. 2003; 1637:142-150.
- [9]Sastre J, Serviddio G, Pereda J, Minana JB, Arduini A, Vendemiale G, Poli G, Pallardo FV, Vina J. Mitochondrial function in liver disease. Front Biosci. 2007; 12:1200-1209.
- [10]Poli G. Pathogenesis of liver fibrosis: role of oxidative stress. Mol Aspects Med. 2000; 21:49-98.
- [11]Lee TY, Wang GJ, Chiu JH, Lin HC. Long-term administration of Salvia miltiorrhiza ameliorates carbon tetrachloride-induced hepatic fibrosis in rats. J Pharm Pharmacol. 2003; 55:1561-1568.
- [12]Vendemiale G, Grattagliano I, Caruso ML, Serviddio G, Valentini AM, Pirrelli M, Altomare E. Increased oxidative stress in dimethylnitrosamine-induced liver fibrosis in the rat: effect of N-acetylcysteine and interferon-alpha. Toxicol Appl Pharmacol. 2001; 175:130-139.
- [13]Wasser S, Ho JM, Ang HK, Tan CE. Salvia miltiorrhiza reduces experimentally-induced hepatic fibrosis in rats. J Hepatol. 1998; 29:760-771.
- [14]Elfalleh W, Ying M, Nasri N, Sheng-Hua H, Guasmi F, Ferchichi A. Fatty acids from Tunisian and Chinese pomegranate (Punica granatum L.) seeds. Int J Food Sci Nutr. 2011; 62:200-206.
- [15]Fischer UA, Carle R, Kammerer DR. Identification and quantification of phenolic compounds from pomegranate (Punica granatum L.) peel, mesocarp, aril and differently produced juices by HPLC-DAD-ESI/MS(n). Food Chem. 2011; 127:807-821.
- [16]Singh RP, Chidambara MK, Jayaprakasha GK. Studies on the antioxidant activity of pomegranate (Punica granatum) peel and seed extracts using in vitro models. J Agric Food Chem. 2002; 50:81-86.
- [17]Aviram M, Dornfeld L. Pomegranate juice consumption inhibits serum angiotensin converting enzyme activity and reduces systolic blood pressure. Atherosclerosis. 2001; 158:195-198.
- [18]Seeram NP, Adams LS, Henning SM, Niu Y, Zhang Y, Nair MG, Heber D. In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice. J Nutr Biochem. 2005; 16:360-367.
- [19]Gomez-Caravaca AM, Verardo V, Toselli M, Segura-Carretero A, Fernandez-Gutierrez A, Caboni MF. Determination of the major phenolic compounds in pomegranate juices by HPLC-DAD-ESI-MS. J Agric Food Chem. 2013; 61:5328-5337.
- [20]Aviram M, Volkova N, Coleman R, Dreher M, Reddy MK, Ferreira D, Rosenblat M. Pomegranate phenolics from the peels, arils, and flowers are antiatherogenic: studies in vivo in atherosclerotic apolipoprotein e-deficient (E 0 ) mice and in vitro in cultured macrophages and lipoproteins. J. Agric. Food Chem. 2008; 56:1148-1157.
- [21]Salwe KJ, Sachdev DO, Bahurupi Y, Kumarappan M. Evaluation of antidiabetic, hypolipedimic and antioxidant activity of hydroalcoholic extract of leaves and fruit peel of Punicagranatum in male Wistar albino rats. J Nat SciBiol Med. 2015; 6:56-62.
- [22]Sadeghipour A, Eidi M, IlchizadehKavgani A, Ghahramani R, Shahabzadeh S, Anissian A. Lipid lowering effect of punicagranatum L. Peel in high lipid diet Fed male rats. Evid Based Complement Alternat Med. 2014; 2014:432650.
- [23]Gozlekci S, Saracoglu O, Onursal E, Ozgen M. Total phenolic distribution of juice, peel, and seed extracts of four pomegranate cultivars. Pharmacogn Mag. 2011; 7:161-164.
- [24]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 Clin Invest. 1998; 102:538-549.
- [25]Yang Y, Nemoto EM, Harvey SA, Subbotin VM, Gandhi CR. Increased hepatic platelet activating factor (PAF) and PAF receptors in carbon tetrachloride induced liver cirrhosis. Gut. 2004; 53:877-883.
- [26]Li C, Luo J, Li L, Cheng M, Huang N, Liu J, Waalkes MP. The collagenolytic effects of the traditional Chinese medicine preparation, Han-Dan-Gan-Le, contribute to reversal of chemical-induced liver fibrosis in rats. Life Sci. 2003; 72:1563-1571.
- [27]Safer AM, Afzal M, Nomani A, Sosamma O, Mousa SA. Curative propensity of green tea extract towards hepatic fibrosis induced by CCl(4): A histopathological study. Exp Ther Med. 2012; 3:781-786.
- [28]Fan W, Shi B, Wei H, Ma X, He X, Feng K. Gamma-aminobutyric acid B receptor improves carbon tetrachloride-induced liver fibrosis in rats. Dig Dis Sci. 2013; 58:1909-1915.
- [29]Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guide for clinicians. CMAJ. 2005; 172:367-379.
- [30]Kim MY, Baik SK, Jang YO, Suk KT, Kim JW, Kim HS, Cho MY, Choi SJ, Um SH, Han KH. Serum hyaluronic acid level: correlation with quantitative measurement of hepatic fibrosis in a cirrhotic rat model. Korean J Hepatol. 2008; 14:159-167.
- [31]Qiu W, Guo K, Yi L, Gong Y, Huang L, Zhong W. Resolvin E1 reduces hepatic fibrosis in mice with infection. Exp Ther Med. 2014; 7:1481-1485.
- [32]Dang SS, Wang BF, Cheng YA, Song P, Liu ZG, Li ZF. Inhibitory effects of saikosaponin-d on CCl4-induced hepatic fibrogenesis in rats. World J Gastroenterol. 2007; 13:557-563.
- [33]Choi YJ, Kim DH, Kim SJ, Kim J, Jeong SI, Chung CH, Yu KY, Kim SY. Decursin attenuates hepatic fibrogenesis through interrupting TGF-beta-mediated NAD(P)H oxidase activation and Smad signaling in vivo and in vitro. Life Sci. 2014; 108:94-103.
- [34]Dooley S, Ten DP. TGF-beta in progression of liver disease. Cell Tissue Res. 2012; 347:245-256.
- [35]Kimura K, Ando K, Ohnishi H, Ishikawa T, Kakumu S, Takemura M, Muto Y, Moriwaki H. Immunopathogenesis of hepatic fibrosis in chronic liver injury induced by repeatedly administered concanavalin A. Int Immunol. 1999; 11:1491-1500.
- [36]Rachfal AW, Brigstock DR. Connective tissue growth factor (CTGF/CCN2) in hepatic fibrosis. Hepatol Res. 2003; 26:1-9.
- [37]Luckey SW, Petersen DR. Activation of Kupffer cells during the course of carbon tetrachloride-induced liver injury and fibrosis in rats. Exp Mol Pathol. 2001; 71:226-240.
- [38]Hernandez-Munoz R, Diaz-Munoz M, Lopez V, Lopez-Barrera F, Yanez L, Vidrio S, Aranda-Fraustro A, Chagoya DSV. Balance between oxidative damage and proliferative potential in an experimental rat model of CCl4-induced cirrhosis: protective role of adenosine administration. Hepatology. 1997; 26:1100-1110.
- [39]Muriel P, Escobar Y. Kupffer cells are responsible for liver cirrhosis induced by carbon tetrachloride. J Appl Toxicol. 2003; 23:103-108.
- [40]Wasser S, Tan CE. Experimental models of hepatic fibrosis in the rat. Ann Acad Med Singapore. 1999; 28:109-111.
- [41]Drewa G, Krzyzynska-Malinowska E, Wozniak A, Protas-Drozd F, Mila-Kierzenkowska C, Rozwodowska M, Kowaliszyn B, Czajkowski R. Activity of superoxide dismutase and catalase and the level of lipid peroxidation products reactive with TBA in patients with psoriasis. Med Sci Monit. 2002; 8:R338-R343.
- [42]Ballatori N, Krance SM, Notenboom S, Shi S, Tieu K, Hammond CL. Glutathione dysregulation and the etiology and progression of human diseases. Biol Chem. 2009; 390:191-214.
- [43]Yin YY, Li WP, Gong HL, Zhu FF, Li WZ, Wu GC. Protective effect of astragaloside on focal cerebral ischemia/reperfusion injury in rats. Am J Chin Med. 2010; 38:517-527.
- [44]Liochev SI, Fridovich I. Mechanism of the peroxidase activity of Cu, Zn superoxide dismutase. Free Radic Biol Med. 2010; 48:1565-1569.
- [45]Rice-Evans CA, Miller NJ, Bolwell PG, Bramley PM, Pridham JB. The relative antioxidant activities of plant-derived polyphenolic flavonoids. Free Radic Res. 1995; 22:375-383.