Comparison between the efficacies of curcumin and puerarin in C57BL/6 mice with steatohepatitis induced by a methionine‑ and choline‑deficient diet

Wang,Yunliang; Li,Jian; Zhuge,Li; Su,Dongmei; Yang,Meijuan; Tao,Shiying; Li,Junxiang

doi:10.3892/etm.2013.1461

Comparison between the efficacies of curcumin and puerarin in C57BL/6 mice with steatohepatitis induced by a methionine‑ and choline‑deficient diet

Authors:
- Yunliang Wang
- Jian Li
- Li Zhuge
- Dongmei Su
- Meijuan Yang
- Shiying Tao
- Junxiang Li
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Affiliations: Dongfang Hospital, Beijing University of Chinese Medicine, Beijing 100078, P.R. China, Preclinical College, Beijing University of Chinese Medicine, Beijing 100029, P.R. China
Published online on: December 24, 2013 https://doi.org/10.3892/etm.2013.1461
Pages: 663-668

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Abstract

Non-alcoholic fatty liver disease (NAFLD) is a prevalent disease, which features an abnormal accumulation of lipids inside hepatocytes. Steatohepatitis plays a critical role in the process resulting in liver fibrosis and cirrhosis. Curcumin and puerarin are herbal products widely used in Asia, which are believed to have therapeutic benefits for alleviating the symptoms of steatohepatitis. In this study, mice models of steatohepatitis induced by a methionine- and choline‑deficient diet (MCD) were established to compare the pharmacological actions of curcumin and puerarin. The results showed that curcumin and puerarin exerted inhibitory effects against MCD-induced steatohepatitis in mice. Briefly, curcumin and puerarin significantly downregulated the levels of tumor necrosis factor‑α in the blood serum of mice (P<0.01, versus the MCD group). In addition, the levels of triglycerides, total cholesterol and low density lipoproteins in the serum were significantly reduced by puerarin treatment (P<0.05, versus the MCD group). The concentration of interleukin‑6 was downregulated by curcumin only (P<0.01, versus the MCD group). Curcumin and puerarin significantly increased the levels of peroxisome proliferator-activated receptor‑γ (PPARγ; P<0.05, versus the MCD group). Moreover, increased nuclear factor‑κB (NF-κB) was markedly attenuated by curcumin (P<0.05, versus the MCD group). In conclusion, curcumin and puerarin appear to exert different actions against steatohepatitis. It is possible that puerarin regulated lipid metabolism in the ‘first hit’ stage through the PPARγ pathway, while curcumin inhibited the inflammatory response in the ‘second hit’ stage through the NF-κB pathway.

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1	Williamson RM, Price JF, Glancy S, et al; Edinburgh Type 2 Diabetes Study Investigators. Prevalence of and risk factors for hepatic steatosis and nonalcoholic fatty liver disease in people with type 2 diabetes: the Edinburgh Type 2 Diabetes Study. Diabetes Care. 34:1139–1144. 2011. View Article : Google Scholar : PubMed/NCBI
2	Valantinas J, Apanaviciene DA, Maroziene L and Sveikata A: The prevalence of metabolic risk factors among outpatients with diagnosed nonalcoholic fatty liver disease in Lithuania. Med Sci Monit. 18:PH57–PH62. 2012. View Article : Google Scholar : PubMed/NCBI
3	Chitturi S and Farrell GC: Etiopathogenesis of nonalcoholic steatohepatitis. Semin Liver Dis. 21:27–41. 2001. View Article : Google Scholar : PubMed/NCBI
4	Reid AE: Nonalcoholic steatohepatitis. Gastroenterology. 121:710–723. 2001. View Article : Google Scholar : PubMed/NCBI
5	Kallwitz ER, McLachlan A and Cotler SJ: Role of peroxisome proliferators-activated receptors in the pathogenesis and treatment of nonalcoholic fatty liver disease. World J Gastroenterol. 14:22–28. 2008. View Article : Google Scholar : PubMed/NCBI
6	Wu CW, Chu ES, Lam CN, et al: PPARgamma is essential for protection against nonalcoholic steatohepatitis. Gene Ther. 17:790–798. 2010. View Article : Google Scholar : PubMed/NCBI
7	Yuhas Y, Berent E, Cohen R and Ashkenazi S: Roles of NF-kappaB activation and peroxisome proliferator-activated receptor gamma inhibition in the effect of rifampin on inducible nitric oxide synthase transcription in human lung epithelial cells. Antimicrob Agents Chemother. 53:1539–1545. 2009. View Article : Google Scholar
8	Sanyal AJ, Mofrad PS, Contos MJ, et al: A pilot study of vitamin E versus vitamin E and pioglitazone for the treatment of nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol. 2:1107–1115. 2004. View Article : Google Scholar : PubMed/NCBI
9	Promrat K, Lutchman G, Uwaifo GI, et al: A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. Hepatology. 39:188–196. 2004. View Article : Google Scholar : PubMed/NCBI
10	Elasy TA and Griffin M: Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association: response to Nesto. Diabetes Care. 27:20962004. View Article : Google Scholar
11	Nesto RW, Bell D, Bonow RO, et al: Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. Diabetes Care. 27:256–263. 2004. View Article : Google Scholar
12	Parulkar AA, Pendergrass ML, Granda-Ayala R, Lee TR and Fonseca VA: Nonhypoglycemic effects of thiazolidinediones. Ann Intern Med. 134:61–71. 2001. View Article : Google Scholar : PubMed/NCBI
13	Seeff LB, Lindsay KL, Bacon BR, Kresina TF and Hoofnagle JH: Complementary and alternative medicine in chronic liver disease. Hepatology. 34:595–603. 2001. View Article : Google Scholar : PubMed/NCBI
14	Ghosh N, Ghosh R, Mandal V and Mandal SC: Recent advances in herbal medicine for treatment of liver diseases. Pharm Biol. 49:970–988. 2011. View Article : Google Scholar : PubMed/NCBI
15	Yao QH, Wang DQ, Cui CC, et al: Curcumin ameliorates left ventricular function in rabbits with pressure overload: inhibition of the remodeling of the left ventricular collagen network associated with suppression of myocardial tumor necrosis factor-alpha and matrix metalloproteinase-2 expression. Biol Pharm Bull. 27:198–202. 2004.
16	Vizzutti F, Provenzano A, Galastri S, et al: Curcumin limits the fibrogenic evolution of experimental steatohepatitis. Lab Invest. 90:104–115. 2010. View Article : Google Scholar : PubMed/NCBI
17	Tang Y, Zheng S and Chen A: Curcumin eliminates leptin’s effects on hepatic stellate cell activation via interrupting leptin signaling. Endocrinology. 150:3011–3020. 2009.
18	Xiao C, Li J, Dong X, et al: Anti-oxidative and TNF-α suppressive activities of puerarin derivative (4AC) in RAW264.7 cells and collagen-induced arthritic rats. Eur J Pharmacol. 666:242–250. 2011.
19	Zheng P, Ji G, Ma Z, et al: Therapeutic effect of puerarin on non-alcoholic rat fatty liver by improving leptin signal transduction through JAK2/STAT3 pathways. Am J Chin Med. 37:69–83. 2009. View Article : Google Scholar : PubMed/NCBI
20	Chung MJ, Sung NJ, Park CS, et al: Antioxidative and hypocholesterolemic activities of water-soluble puerarin glycosides in HepG2 cells and in C57 BL/6J mice. Eur J Pharmacol. 578:159–170. 2008. View Article : Google Scholar : PubMed/NCBI
21	Xiao LZ, Gao LJ and Ma SC: Comparative study on effects of puerarin and granulocyte colony-stimulating factor in treating acute myocardial infarction. Zhongguo Zhong Xi Yi Jie He Za Zhi. 25:210–213. 2005.(In Chinese).
22	Dowman JK, Tomlinson JW and Newsome PN: Pathogenesis of non-alcoholic fatty liver disease. QJM. 103:71–83. 2010. View Article : Google Scholar : PubMed/NCBI
23	Fon Tacer K and Rozman D: Nonalcoholic Fatty liver disease: focus on lipoprotein and lipid deregulation. J Lipids. 2011:7839762011.PubMed/NCBI
24	Day CP and James OF: Steatohepatitis: a tale of two ‘hits’? Gastroenterology. 114:842–845. 1998.
25	Postic C and Girard J: Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice. J Clin Invest. 118:829–838. 2008. View Article : Google Scholar : PubMed/NCBI
26	Kugelmas M, Hill DB, Vivian B, Marsano L and McClain CJ: Cytokines and NASH: a pilot study of the effects of lifestyle modification and vitamin E. Hepatology. 38:413–419. 2003. View Article : Google Scholar : PubMed/NCBI
27	Tilg H and Diehl AM: Cytokines in alcoholic and nonalcoholic steatohepatitis. N Engl J Med. 343:1467–1476. 2000. View Article : Google Scholar : PubMed/NCBI
28	Tarantino G, Conca P, Pasanisi F, et al: Could inflammatory markers help diagnose nonalcoholic steatohepatitis? Eur J Gastroenterol Hepatol. 21:504–511. 2009. View Article : Google Scholar : PubMed/NCBI
29	Cai D, Yuan M, Frantz DF, et al: Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med. 11:183–190. 2005. View Article : Google Scholar : PubMed/NCBI
30	Gaemers IC and Groen AK: New insights in the pathogenesis of non-alcoholic fatty liver disease. Curr Opin Lipidol. 17:268–273. 2006. View Article : Google Scholar : PubMed/NCBI
31	Reddy JK: Nonalcoholic steatosis and steatohepatitis. III Peroxisomal beta-oxidation, PPAR alpha, and steatohepatitis. Am J Physiol Gastrointest Liver Physiol. 281:G1333–G1339. 2001.PubMed/NCBI
32	Anstee QM and Goldin RD: Mouse models in non-alcoholic fatty liver disease and steatohepatitis research. Int J Exp Pathol. 87:1–16. 2006. View Article : Google Scholar : PubMed/NCBI
33	Vance JE and Vance DE: The role of phosphatidylcholine biosynthesis in the secretion of lipoproteins from hepatocytes. Can J Biochem Cell Biol. 63:870–881. 1985. View Article : Google Scholar : PubMed/NCBI
34	Yao ZM and Vance DE: The active synthesis of phosphatidylcholine is required for very low density lipoprotein secretion from rat hepatocytes. J Biol Chem. 263:2998–3004. 1988.PubMed/NCBI
35	Gyamfi MA, Damjanov I, French S and Wan YJ: The pathogenesis of ethanol versus methionine and choline deficient diet-induced liver injury. Biochem Pharmacol. 75:981–995. 2008. View Article : Google Scholar : PubMed/NCBI