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Published in: BMC Complementary Medicine and Therapies 1/2017

Open Access 01-12-2017 | Research article

Effect of ginseng extract on the TGF-β1 signaling pathway in CCl4-induced liver fibrosis in rats

Authors: Mohamed M. Hafez, Sherifa S. Hamed, Manal F. El-Khadragy, Zeinab K. Hassan, Salim S. Al Rejaie, Mohamed M. Sayed-Ahmed, Naif O. Al-Harbi, Khalid A. Al-Hosaini, Mohamed M. Al-Harbi, Ali R. Alhoshani, Othman A. Al-Shabanah, Shakir Dekhal Alsharari

Published in: BMC Complementary Medicine and Therapies | Issue 1/2017

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Abstract

Background

Liver diseases are major global health problems. Ginseng extract has antioxidant, immune-modulatory and anti-inflammatory activities. This study investigated the effect of ginseng extract on carbon tetrachloride (CCl4)-induced liver fibrosis in rats.

Methods

Male Wistar rats were divided into four groups: control group, ginseng group, CCl4 group and CCl4 + ginseng group. Liver injury was induced by the intraperitoneal (I.P) injection of 3 ml/kg CCl4 (30% in olive oil) weekly for 8 weeks. The control group was I.P injected with olive oil. The expression of genes encoding transforming growth factor beta (TGF-β), type I TGF-β receptor (TβR-1), type II TGF-β receptor (TβR-II), mothers against decapentaplegic homolog 2 (Smad2), Smad3, Smad4, matrix metalloproteinase 2 (MMP2), MMP9, tissue inhibitor matrix metalloproteinase-1 (TIMP-1), Collagen 1a2 (Col1a2), Collagen 3a1 (Col3a1), interleukin-8 (IL-8) and interleukin -10 (IL-10) were measured by real-time PCR.

Results

Treatment with ginseng extract decreased hepatic fat deposition and lowered hepatic reticular fiber accumulation compared with the CCl4 group. The CCl4 group showed a significant increase in hepatotoxicity biomarkers and up-regulation of the expression of genes encoding TGF-β, TβR-I, TβR-II, MMP2, MMP9, Smad-2,-3, -4, and IL-8 compared with the control group. However, CCl4 administration resulted in the significant down-regulation of IL-10 mRNA expression compared with the control group. Interestingly, ginseng extract supplementation completely reversed the biochemical markers of hepatotoxicity and the gene expression alterations induced by CCl4.

Conclusion

ginseng extract had an anti‐fibrosis effect via the regulation of the TGF‐β1/Smad signaling pathway in the CCl4‐induced liver fibrosis model. The major target was the inhibition of the expression of TGF‐β1, Smad2, and Smad3.
Literature
1.
go back to reference Turner PV, Brabb T, Pekow C, Vasbinder MA. Administration of substances to laboratory animals: routes of administration and factors to consider. J Am Assoc Lab Anim Sci. 2011;50(5):600–13.PubMedPubMedCentral Turner PV, Brabb T, Pekow C, Vasbinder MA. Administration of substances to laboratory animals: routes of administration and factors to consider. J Am Assoc Lab Anim Sci. 2011;50(5):600–13.PubMedPubMedCentral
2.
go back to reference Labarga P, Fernandez-Montero JV, de Mendoza C, Barreiro P, Pinilla J, Soriano V. Liver fibrosis progression despite HCV cure with antiviral therapy in HIV-HCV-coinfected patients. Antivir Ther. 2015;20(3):329–34.CrossRefPubMed Labarga P, Fernandez-Montero JV, de Mendoza C, Barreiro P, Pinilla J, Soriano V. Liver fibrosis progression despite HCV cure with antiviral therapy in HIV-HCV-coinfected patients. Antivir Ther. 2015;20(3):329–34.CrossRefPubMed
4.
go back to reference Peng YC, Lin CL, Hsu WY, Chang CS, Yeh HZ, Kao CH. Risk of Liver Cirrhosis in Patients with Tuberculosis: A Nationwide Cohort Study. Eur J Clin Investig 2015;45(7):663–9 Peng YC, Lin CL, Hsu WY, Chang CS, Yeh HZ, Kao CH. Risk of Liver Cirrhosis in Patients with Tuberculosis: A Nationwide Cohort Study. Eur J Clin Investig 2015;45(7):663–9
5.
6.
go back to reference Liu T, Wang X, Karsdal MA, Leeming DJ, Genovese F. Molecular serum markers of liver fibrosis. Biomark Insights. 2012;7:105–17.PubMedPubMedCentral Liu T, Wang X, Karsdal MA, Leeming DJ, Genovese F. Molecular serum markers of liver fibrosis. Biomark Insights. 2012;7:105–17.PubMedPubMedCentral
7.
go back to reference Singh N, Kamath V, Narasimhamurthy K, Rajini PS. Protective effect of potato peel extract against carbon tetrachloride-induced liver injury in rats. Environ Toxicol Pharmacol. 2008;26(2):241–6.CrossRefPubMed Singh N, Kamath V, Narasimhamurthy K, Rajini PS. Protective effect of potato peel extract against carbon tetrachloride-induced liver injury in rats. Environ Toxicol Pharmacol. 2008;26(2):241–6.CrossRefPubMed
8.
go back to reference Liedtke C, Luedde T, Sauerbruch T, Scholten D, Streetz K, Tacke F, Tolba R, Trautwein C, Trebicka J, Weiskirchen R. Experimental liver fibrosis research: update on animal models, legal issues and translational aspects. Fibrogenesis Tissue Repair. 2013;6(1):19.CrossRefPubMedPubMedCentral Liedtke C, Luedde T, Sauerbruch T, Scholten D, Streetz K, Tacke F, Tolba R, Trautwein C, Trebicka J, Weiskirchen R. Experimental liver fibrosis research: update on animal models, legal issues and translational aspects. Fibrogenesis Tissue Repair. 2013;6(1):19.CrossRefPubMedPubMedCentral
9.
go back to reference Siegmund SV, Brenner DA. Molecular pathogenesis of alcohol-induced hepatic fibrosis. Alcohol Clin Exp Res. 2005;29(11 Suppl):102S–9S.CrossRefPubMed Siegmund SV, Brenner DA. Molecular pathogenesis of alcohol-induced hepatic fibrosis. Alcohol Clin Exp Res. 2005;29(11 Suppl):102S–9S.CrossRefPubMed
10.
go back to reference Weber LW, Boll M, Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit Rev Toxicol. 2003;33(2):105–36.CrossRefPubMed Weber LW, Boll M, Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit Rev Toxicol. 2003;33(2):105–36.CrossRefPubMed
11.
go back to reference Lu DH, Guo XY, Qin SY, Luo W, Huang XL, Chen M, Wang JX, Ma SJ, Yang XW, Jiang HX. Interleukin-22 ameliorates liver fibrogenesis by attenuating hepatic stellate cell activation and downregulating the levels of inflammatory cytokines. World J Gastroenterol. 2015;21(5):1531–45.CrossRefPubMedPubMedCentral Lu DH, Guo XY, Qin SY, Luo W, Huang XL, Chen M, Wang JX, Ma SJ, Yang XW, Jiang HX. Interleukin-22 ameliorates liver fibrogenesis by attenuating hepatic stellate cell activation and downregulating the levels of inflammatory cytokines. World J Gastroenterol. 2015;21(5):1531–45.CrossRefPubMedPubMedCentral
12.
go back to reference Wang Y, Liu W, Liu X, Sheng M, Pei Y, Lei R, Zhang S, Tao R. Role of liver in modulating the release of inflammatory cytokines involved in lung and multiple organ dysfunction in severe acute pancreatitis. Cell Biochem Biophys. 2015;71(2):765–76.CrossRefPubMed Wang Y, Liu W, Liu X, Sheng M, Pei Y, Lei R, Zhang S, Tao R. Role of liver in modulating the release of inflammatory cytokines involved in lung and multiple organ dysfunction in severe acute pancreatitis. Cell Biochem Biophys. 2015;71(2):765–76.CrossRefPubMed
13.
go back to reference Gressner AM, Weiskirchen R, Breitkopf K, Dooley S. Roles of TGF-beta in hepatic fibrosis. Front Biosci. 2002;7:d793–807.CrossRefPubMed Gressner AM, Weiskirchen R, Breitkopf K, Dooley S. Roles of TGF-beta in hepatic fibrosis. Front Biosci. 2002;7:d793–807.CrossRefPubMed
14.
go back to reference Wang J, Qiao L, Li Y, Yang G. Ginsenoside Rb1 attenuates intestinal ischemia-reperfusion- induced liver injury by inhibiting NF-kappaB activation. Exp Mol Med. 2008;40(6):686–98.CrossRefPubMedPubMedCentral Wang J, Qiao L, Li Y, Yang G. Ginsenoside Rb1 attenuates intestinal ischemia-reperfusion- induced liver injury by inhibiting NF-kappaB activation. Exp Mol Med. 2008;40(6):686–98.CrossRefPubMedPubMedCentral
15.
go back to reference Jung CH, Seog HM, Choi IW, Choi HD, Cho HY. Effects of wild ginseng (panax ginseng C.A. Meyer) leaves on lipid peroxidation levels and antioxidant enzyme activities in streptozotocin diabetic rats. J Ethnopharmacol. 2005;98(3):245–50.CrossRefPubMed Jung CH, Seog HM, Choi IW, Choi HD, Cho HY. Effects of wild ginseng (panax ginseng C.A. Meyer) leaves on lipid peroxidation levels and antioxidant enzyme activities in streptozotocin diabetic rats. J Ethnopharmacol. 2005;98(3):245–50.CrossRefPubMed
16.
go back to reference Huang YC, Chen CT, Chen SC, Lai PH, Liang HC, Chang Y, Yu LC, Sung HW. A natural compound (ginsenoside Re) isolated from panax ginseng as a novel angiogenic agent for tissue regeneration. Pharm Res. 2005;22(4):636–46.CrossRefPubMed Huang YC, Chen CT, Chen SC, Lai PH, Liang HC, Chang Y, Yu LC, Sung HW. A natural compound (ginsenoside Re) isolated from panax ginseng as a novel angiogenic agent for tissue regeneration. Pharm Res. 2005;22(4):636–46.CrossRefPubMed
18.
go back to reference Cicero AF, Vitale G, Savino G, Arletti R. Panax notoginseng (burk.) effects on fibrinogen and lipid plasma level in rats fed on a high-fat diet. Phytother Res. 2003;17(2):174–8.CrossRefPubMed Cicero AF, Vitale G, Savino G, Arletti R. Panax notoginseng (burk.) effects on fibrinogen and lipid plasma level in rats fed on a high-fat diet. Phytother Res. 2003;17(2):174–8.CrossRefPubMed
19.
go back to reference Choi KT. Botanical characteristics, pharmacological effects and medicinal components of Korean panax ginseng C a Meyer. Acta Pharmacol Sin. 2008;29(9):1109–18.CrossRefPubMed Choi KT. Botanical characteristics, pharmacological effects and medicinal components of Korean panax ginseng C a Meyer. Acta Pharmacol Sin. 2008;29(9):1109–18.CrossRefPubMed
20.
go back to reference Yang XW, Hattori M, Namba T, Chen DF, Xu GJ. Anti-lipid peroxidative effect of an extract of the stems of kadsura heteroclita and its major constituent, kadsurin, in mice. Chem Pharm Bull. 1992;40(2):406–9.CrossRefPubMed Yang XW, Hattori M, Namba T, Chen DF, Xu GJ. Anti-lipid peroxidative effect of an extract of the stems of kadsura heteroclita and its major constituent, kadsurin, in mice. Chem Pharm Bull. 1992;40(2):406–9.CrossRefPubMed
21.
go back to reference Lee HU, Bae EA, Han MJ, Kim NJ, Kim DH. Hepatoprotective effect of ginsenoside Rb1 and compound K on tert-butyl hydroperoxide-induced liver injury. Liver Int. 2005;25(5):1069–73.CrossRefPubMed Lee HU, Bae EA, Han MJ, Kim NJ, Kim DH. Hepatoprotective effect of ginsenoside Rb1 and compound K on tert-butyl hydroperoxide-induced liver injury. Liver Int. 2005;25(5):1069–73.CrossRefPubMed
22.
go back to reference Park EK, Shin YW, Lee HU, Kim SS, Lee YC, Lee BY, Kim DH. Inhibitory effect of ginsenoside Rb1 and compound K on NO and prostaglandin E2 biosyntheses of RAW264.7 cells induced by lipopolysaccharide. Biol Pharm Bull. 2005;28(4):652–6.CrossRefPubMed Park EK, Shin YW, Lee HU, Kim SS, Lee YC, Lee BY, Kim DH. Inhibitory effect of ginsenoside Rb1 and compound K on NO and prostaglandin E2 biosyntheses of RAW264.7 cells induced by lipopolysaccharide. Biol Pharm Bull. 2005;28(4):652–6.CrossRefPubMed
23.
go back to reference Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010;8(6):e1000412.CrossRefPubMedPubMedCentral Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010;8(6):e1000412.CrossRefPubMedPubMedCentral
24.
go back to reference Khan RA, Khan MR, Sahreen S. CCl4-induced hepatotoxicity: protective effect of rutin on p53, CYP2E1 and the antioxidative status in rat. BMC Complement Altern Med. 2012;12:178.CrossRefPubMedPubMedCentral Khan RA, Khan MR, Sahreen S. CCl4-induced hepatotoxicity: protective effect of rutin on p53, CYP2E1 and the antioxidative status in rat. BMC Complement Altern Med. 2012;12:178.CrossRefPubMedPubMedCentral
25.
go back to reference Karadeniz A, Cemek M, Simsek N. The effects of panax ginseng and spirulina platensis on hepatotoxicity induced by cadmium in rats. Ecotoxicol Environ Saf. 2009;72(1):231–5.CrossRefPubMed Karadeniz A, Cemek M, Simsek N. The effects of panax ginseng and spirulina platensis on hepatotoxicity induced by cadmium in rats. Ecotoxicol Environ Saf. 2009;72(1):231–5.CrossRefPubMed
26.
go back to reference Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957;226(1):497–509.PubMed Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957;226(1):497–509.PubMed
27.
go back to reference Hafez MM, Al-Shabanah OA, Al-Harbi NO, Al-Harbi MM, Al-Rejaie SS, Alsurayea SM, Sayed-Ahmed MM. Association between paraoxonases gene expression and oxidative stress in hepatotoxicity induced by CCl4. Oxid Med Cell Longev. 2014;2014:893212.CrossRefPubMedPubMedCentral Hafez MM, Al-Shabanah OA, Al-Harbi NO, Al-Harbi MM, Al-Rejaie SS, Alsurayea SM, Sayed-Ahmed MM. Association between paraoxonases gene expression and oxidative stress in hepatotoxicity induced by CCl4. Oxid Med Cell Longev. 2014;2014:893212.CrossRefPubMedPubMedCentral
28.
go back to reference Tacke F, Luedde T, Trautwein C. Inflammatory pathways in liver homeostasis and liver injury. Clin Rev Allergy Immunol. 2009;36(1):4–12.CrossRefPubMed Tacke F, Luedde T, Trautwein C. Inflammatory pathways in liver homeostasis and liver injury. Clin Rev Allergy Immunol. 2009;36(1):4–12.CrossRefPubMed
30.
go back to reference Basu S. Carbon tetrachloride-induced lipid peroxidation: eicosanoid formation and their regulation by antioxidant nutrients. Toxicology. 2003;189(1-2):113–27.CrossRefPubMed Basu S. Carbon tetrachloride-induced lipid peroxidation: eicosanoid formation and their regulation by antioxidant nutrients. Toxicology. 2003;189(1-2):113–27.CrossRefPubMed
31.
go back to reference Aruoma OI. Methodological considerations for characterizing potential antioxidant actions of bioactive components in plant foods. Mutat Res. 2003;523–524:9–20.CrossRefPubMed Aruoma OI. Methodological considerations for characterizing potential antioxidant actions of bioactive components in plant foods. Mutat Res. 2003;523–524:9–20.CrossRefPubMed
32.
go back to reference Emzhik M, Rahimi-Moghaddam P, Ebrahimi SA, Keyhanfar F, Moazzam AS. Commentary on prevention a possible drug-drug interaction: is concurrent administration of orlistat and pioglitazone increase the risk of durg-induced hepatotoxicity? Int J Prev Med. 2015;6:16.CrossRefPubMedPubMedCentral Emzhik M, Rahimi-Moghaddam P, Ebrahimi SA, Keyhanfar F, Moazzam AS. Commentary on prevention a possible drug-drug interaction: is concurrent administration of orlistat and pioglitazone increase the risk of durg-induced hepatotoxicity? Int J Prev Med. 2015;6:16.CrossRefPubMedPubMedCentral
33.
go back to reference Ikeda T. Idiosyncratic drug hepatotoxicity: strategy for prevention and proposed mechanism. Curr Med Chem. 2015;22(4):528–37.CrossRefPubMed Ikeda T. Idiosyncratic drug hepatotoxicity: strategy for prevention and proposed mechanism. Curr Med Chem. 2015;22(4):528–37.CrossRefPubMed
34.
go back to reference Kim HJ, Chun YJ, Park JD, Kim SI, Roh JK, Jeong TC. Protection of rat liver microsomes against carbon tetrachloride-induced lipid peroxidation by red ginseng saponin through cytochrome P450 inhibition. Planta Med. 1997;63(5):415–8.CrossRefPubMed Kim HJ, Chun YJ, Park JD, Kim SI, Roh JK, Jeong TC. Protection of rat liver microsomes against carbon tetrachloride-induced lipid peroxidation by red ginseng saponin through cytochrome P450 inhibition. Planta Med. 1997;63(5):415–8.CrossRefPubMed
35.
go back to reference Kitts DD, Wijewickreme AN, Hu C. Antioxidant properties of a north american ginseng extract. Mol Cell Biochem. 2000;203(1–2):1–10.CrossRefPubMed Kitts DD, Wijewickreme AN, Hu C. Antioxidant properties of a north american ginseng extract. Mol Cell Biochem. 2000;203(1–2):1–10.CrossRefPubMed
36.
37.
go back to reference Jaeschke H. Mechanisms of liver injury. II. Mechanisms of neutrophil-induced liver cell injury during hepatic ischemia-reperfusion and other acute inflammatory conditions. Am J Physiol Gastrointest Liver Physiol. 2006;290(6):G1083–8.CrossRefPubMed Jaeschke H. Mechanisms of liver injury. II. Mechanisms of neutrophil-induced liver cell injury during hepatic ischemia-reperfusion and other acute inflammatory conditions. Am J Physiol Gastrointest Liver Physiol. 2006;290(6):G1083–8.CrossRefPubMed
38.
go back to reference Jaeschke H. Neutrophil-mediated tissue injury in alcoholic hepatitis. Alcohol. 2002, 27(1):23-27. Jaeschke H. Neutrophil-mediated tissue injury in alcoholic hepatitis. Alcohol. 2002, 27(1):23-27.
39.
go back to reference Zimmermann HW, Seidler S, Gassler N, Nattermann J, Luedde T, Trautwein C, Tacke F. Interleukin-8 is activated in patients with chronic liver diseases and associated with hepatic macrophage accumulation in human liver fibrosis. PLoS One. 2011;6(6):e21381.CrossRefPubMedPubMedCentral Zimmermann HW, Seidler S, Gassler N, Nattermann J, Luedde T, Trautwein C, Tacke F. Interleukin-8 is activated in patients with chronic liver diseases and associated with hepatic macrophage accumulation in human liver fibrosis. PLoS One. 2011;6(6):e21381.CrossRefPubMedPubMedCentral
40.
go back to reference Ramaiah SK, Jaeschke H. Role of neutrophils in the pathogenesis of acute inflammatory liver injury. Toxicol Pathol. 2007;35(6):757–66.CrossRefPubMed Ramaiah SK, Jaeschke H. Role of neutrophils in the pathogenesis of acute inflammatory liver injury. Toxicol Pathol. 2007;35(6):757–66.CrossRefPubMed
41.
go back to reference Escudero-Lourdes C, Wu T, Camarillo JM, Gandolfi AJ. Interleukin-8 (IL-8) over-production and autocrine cell activation are key factors in monomethylarsonous acid [MMA(III)]-induced malignant transformation of urothelial cells. Toxicol Appl Pharmacol. 2012;258(1):10–8.CrossRefPubMed Escudero-Lourdes C, Wu T, Camarillo JM, Gandolfi AJ. Interleukin-8 (IL-8) over-production and autocrine cell activation are key factors in monomethylarsonous acid [MMA(III)]-induced malignant transformation of urothelial cells. Toxicol Appl Pharmacol. 2012;258(1):10–8.CrossRefPubMed
42.
go back to reference Miller AM, Wang H, Bertola A, Park O, Horiguchi N, Ki SH, Yin S, Lafdil F, Gao B. Inflammation-associated interleukin-6/signal transducer and activator of transcription 3 activation ameliorates alcoholic and nonalcoholic fatty liver diseases in interleukin-10-deficient mice. Hepatology. 2011;54(3):846–56.CrossRefPubMedPubMedCentral Miller AM, Wang H, Bertola A, Park O, Horiguchi N, Ki SH, Yin S, Lafdil F, Gao B. Inflammation-associated interleukin-6/signal transducer and activator of transcription 3 activation ameliorates alcoholic and nonalcoholic fatty liver diseases in interleukin-10-deficient mice. Hepatology. 2011;54(3):846–56.CrossRefPubMedPubMedCentral
43.
go back to reference Thompson K, Maltby J, Fallowfield J, McAulay M, Millward-Sadler H, Sheron N. Interleukin-10 expression and function in experimental murine liver inflammation and fibrosis. Hepatology. 1998;28(6):1597–606.CrossRefPubMed Thompson K, Maltby J, Fallowfield J, McAulay M, Millward-Sadler H, Sheron N. Interleukin-10 expression and function in experimental murine liver inflammation and fibrosis. Hepatology. 1998;28(6):1597–606.CrossRefPubMed
44.
go back to reference Huang YH, Shi MN, Zheng WD, Zhang LJ, Chen ZX, Wang XZ. Therapeutic effect of interleukin-10 on CCl4-induced hepatic fibrosis in rats. World J Gastroenterol. 2006;12(9):1386–91.CrossRefPubMedPubMedCentral Huang YH, Shi MN, Zheng WD, Zhang LJ, Chen ZX, Wang XZ. Therapeutic effect of interleukin-10 on CCl4-induced hepatic fibrosis in rats. World J Gastroenterol. 2006;12(9):1386–91.CrossRefPubMedPubMedCentral
45.
go back to reference Yu J, Wu CW, Chu ES, Hui AY, Cheng AS, Go MY, Ching AK, Chui YL, Chan HL, Sung JJ. Elucidation of the role of COX-2 in liver fibrogenesis using transgenic mice. Biochem Biophys Res Commun. 2008;372(4):571–7.CrossRefPubMed Yu J, Wu CW, Chu ES, Hui AY, Cheng AS, Go MY, Ching AK, Chui YL, Chan HL, Sung JJ. Elucidation of the role of COX-2 in liver fibrogenesis using transgenic mice. Biochem Biophys Res Commun. 2008;372(4):571–7.CrossRefPubMed
46.
go back to reference 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(3):538–49.CrossRefPubMedPubMedCentral 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(3):538–49.CrossRefPubMedPubMedCentral
47.
go back to reference Fan X, Zhang Q, Li S, Lv Y, Su H, Jiang H, Hao Z. Attenuation of CCl4-induced hepatic fibrosis in mice by vaccinating against TGF-beta1. PLoS One. 2013;8(12):e82190.CrossRefPubMedPubMedCentral Fan X, Zhang Q, Li S, Lv Y, Su H, Jiang H, Hao Z. Attenuation of CCl4-induced hepatic fibrosis in mice by vaccinating against TGF-beta1. PLoS One. 2013;8(12):e82190.CrossRefPubMedPubMedCentral
48.
go back to reference Duarte S, Baber J, Fujii T, Coito AJ. Matrix metalloproteinases in liver injury, repair and fibrosis. Matrix Biol. 2015;44-46C:147–56.CrossRef Duarte S, Baber J, Fujii T, Coito AJ. Matrix metalloproteinases in liver injury, repair and fibrosis. Matrix Biol. 2015;44-46C:147–56.CrossRef
49.
go back to reference Knittel T, Mehde M, Grundmann A, Saile B, Scharf JG, Ramadori G. Expression of matrix metalloproteinases and their inhibitors during hepatic tissue repair in the rat. Histochem Cell Biol. 2000;113(6):443–53.PubMed Knittel T, Mehde M, Grundmann A, Saile B, Scharf JG, Ramadori G. Expression of matrix metalloproteinases and their inhibitors during hepatic tissue repair in the rat. Histochem Cell Biol. 2000;113(6):443–53.PubMed
50.
go back to reference Kossakowska AE, Edwards DR, Lee SS, Urbanski LS, Stabbler AL, Zhang CL, Phillips BW, Zhang Y, Urbanski SJ. Altered balance between matrix metalloproteinases and their inhibitors in experimental biliary fibrosis. Am J Pathol. 1998;153(6):1895–902.CrossRefPubMedPubMedCentral Kossakowska AE, Edwards DR, Lee SS, Urbanski LS, Stabbler AL, Zhang CL, Phillips BW, Zhang Y, Urbanski SJ. Altered balance between matrix metalloproteinases and their inhibitors in experimental biliary fibrosis. Am J Pathol. 1998;153(6):1895–902.CrossRefPubMedPubMedCentral
51.
go back to reference Lo YT, Tsai YH, Wu SJ, Chen JR, Chao JC. Ginsenoside Rb1 inhibits cell activation and liver fibrosis in rat hepatic stellate cells. J Med Food. 2011;14(10):1135–43.CrossRefPubMed Lo YT, Tsai YH, Wu SJ, Chen JR, Chao JC. Ginsenoside Rb1 inhibits cell activation and liver fibrosis in rat hepatic stellate cells. J Med Food. 2011;14(10):1135–43.CrossRefPubMed
52.
go back to reference Sadasivan SK, Siddaraju N, Khan KM, Vasamsetti B, Kumar NR, Haridas V, Reddy MB, Baggavalli S, Oommen AM, Pralhada Rao R. Developing an in vitro screening assay platform for evaluation of antifibrotic drugs using precision-cut liver slices. Fibrogenesis Tissue Repair. 2015;8(1):1.CrossRefPubMed Sadasivan SK, Siddaraju N, Khan KM, Vasamsetti B, Kumar NR, Haridas V, Reddy MB, Baggavalli S, Oommen AM, Pralhada Rao R. Developing an in vitro screening assay platform for evaluation of antifibrotic drugs using precision-cut liver slices. Fibrogenesis Tissue Repair. 2015;8(1):1.CrossRefPubMed
53.
54.
go back to reference Liu Y, Wang LF, Zou HF, Song XY, Xu HF, Lin P, Zheng HH, Yu XG. Expression and location of Smad2, 4 mRNAs during and after liver fibrogenesis of rats. World J Gastroenterol. 2006;12(10):1577–82.CrossRefPubMedPubMedCentral Liu Y, Wang LF, Zou HF, Song XY, Xu HF, Lin P, Zheng HH, Yu XG. Expression and location of Smad2, 4 mRNAs during and after liver fibrogenesis of rats. World J Gastroenterol. 2006;12(10):1577–82.CrossRefPubMedPubMedCentral
55.
go back to reference Liu L, Li X-m, Chen L, Feng Q, Xu L, Hu Y-y, Peng J-h. The effect of gypenosides on TGF-β1/smad pathway in liver FibrosisInduced by carbon tetrachloride in rats. Int J Integr Med. 2003;1(23):1–6. Liu L, Li X-m, Chen L, Feng Q, Xu L, Hu Y-y, Peng J-h. The effect of gypenosides on TGF-β1/smad pathway in liver FibrosisInduced by carbon tetrachloride in rats. Int J Integr Med. 2003;1(23):1–6.
56.
go back to reference Chang HF, Lin YH, Chu CC, Wu SJ, Tsai YH, Chao JC. Protective effects of ginkgo biloba, panax ginseng, and schizandra chinensis extract on liver injury in rats. Am J Chin Med. 2007;35(6):995–1009.CrossRefPubMed Chang HF, Lin YH, Chu CC, Wu SJ, Tsai YH, Chao JC. Protective effects of ginkgo biloba, panax ginseng, and schizandra chinensis extract on liver injury in rats. Am J Chin Med. 2007;35(6):995–1009.CrossRefPubMed
Metadata
Title
Effect of ginseng extract on the TGF-β1 signaling pathway in CCl4-induced liver fibrosis in rats
Authors
Mohamed M. Hafez
Sherifa S. Hamed
Manal F. El-Khadragy
Zeinab K. Hassan
Salim S. Al Rejaie
Mohamed M. Sayed-Ahmed
Naif O. Al-Harbi
Khalid A. Al-Hosaini
Mohamed M. Al-Harbi
Ali R. Alhoshani
Othman A. Al-Shabanah
Shakir Dekhal Alsharari
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2017
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-016-1507-0

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