Regulating effect of berberine on macrophage phenotype transformation in hepatic tissue of mice with methionine-choline deficiency diet induced non-alcoholic steatohepatitis

doi:10.3969/j.issn.0529-1356.2014.05.009

Abstract

Abstract:

Objective To determine the efficacy of berberine in the treatment of non-alcoholic steatohepatitis (NASH), and to investigate the regulating effect on macrophage phenotype transformation in hepatic tissue on methionine-choline deficiency (MCD) diet induced NASH mice. Methods Fourty male C57BL/6 mice were randomly divided into 4 groups (10 mice per group): the normal group (fed with normal diet), the NASH model group (fed with MCD diet), rosiglitazone treatment group (30mg/kg) and berberine treatment group (150mg/kg). Drugs were adopted in the preventive intervention method for 2 weeks. The hepatic histopathological method was adopted to evaluate the drug therapeutic effect. The serum levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-6, and IL-10 were examined with ELISA method. M1 and M2 phenotype were detected by flow cytometry. Results The results showed berberine improved the degree of hepatic histopathology. Berberine not only reduced the level of TNF-α, but also increased the level of IL-10 in serum on NASH mice significantly (P<0.05). Flow cytometry data indicated that berberine decreased M1 type macrophages and increased M2 type macrophages in liver tissue. The ratio of M1/M2 was significantly decreased in berberine and rosiglitazone treated group (P<0.01). Conclusion Berberine may improve the hepatic pathological process in MCD diet induced NASH model possibly through modulating macrophage phenotype transformation, i.e. The ratio of M2 type is more than M1 type in hepatic tissue, and increasing anti-inflammatory cytokines.

Key words: Berberine, Non-alcholic steatohepatitis, Macrophage, Phenotype transformation, Flow cytometry, Mouse

ZHANG Hui-qin LIU Ze-zhou XU Chang LIU Xin LOU Jin-li LI Jian NIU Jian-zhao HAO Yu *. Regulating effect of berberine on macrophage phenotype transformation in hepatic tissue of mice with methionine-choline deficiency diet induced non-alcoholic steatohepatitis[J]. AAS, 2014, 45(5): 633-638.

References

［1］Fan JG, Farrell GC. Epidemiology of non-alcoholic fatty liver disease in China ［J］. J Hepatol, 2009，50(1): 204-210.
［2］Shi JP, Fan JG. Effects of hepatoprotectants in the treatment of nonalcoholic fatty liver disease ［J］. World Clinical Drugs, 2010, 31 (9): 526-531. (in Chinese)
施军平，范建高. 保肝抗炎药物在非酒精性脂肪性肝病治疗中的作用［J］. 世界临床医药， 2010, 31 (9): 526-531.
［3］Neyrinck AM, Cani PD, Dewulf EM, et al. Critical role of Kuffer cells in the management of diet-induced diabetes and obesity ［J］. Biochem Biophys Res Commun, 2009, 385 (3):351-356.［4］Maina V, Sutti S, Locatelli I, et al. Bias in macrophage activation pattern influences non-alcoholic steatohepatitis (NASH) in mice ［J］. Clin Sci, 2012, 122(11):545-553.
［5］Bouhlel MA, Derudas B, Rigamonti E, et al. PPAR-gamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties ［J］. Cell Metlab, 2007, 6(2): 137-143.
［6］Charo IF, Macrophage polarization and insulin resistance: PPAR-gamma in control ［J］. Cell Metlab, 2007, 6(2):96-98.
［7］Wu CW, Chu ES, Lam CN, et al. PPAR-gamma is essential for protection against nonalcoholic steatohepatitis ［J］. Gene Ther, 2010, 17 (6): 790-798.
［8］Nan, YM, Fu N, Wu WJ, et al. Rosiglitazone prevents nutritional fibrosis and steatohepatitis in mice［J］. Scand J Gastroenterol, 2009, 44(3): 358-365.
［9］Kallwitz ER, McLachlan A, Cotler SJ. Role of peroxisome proliferators-activated receptors in the pathogenesis and treatment of nonalcoholic fatty liver disease ［J］. World J Gastroeuterol, 2008, 14 (1): 22-28.
［10］Xing LJ, Zhang L, Liu T, et al. Berberine reducing insulin resistance by up-regulating IRS-2 mRNA expression in nonalcoholic fatty liver disease (NAFLD) rat liver［J］. Eur J Pharmacol, 2011, 668 (3):467-471.
［11］Yang QH, Hu SP, Zhang YP, et al. Effect of berberine on expressions of uncoupling protein-2 mRNA and protein in hepatic tissue of non-alcoholic fatty liver disease in rats［J］. Chin J Integr Med, 2011, 17(3):205-211.
［12］Li J, Hao Y, Zhang YL, et al. Berberine inhibits tumor-associated macrophages in subcutaneous tumor of mice ［J］. Chinese Journal of Histochemistry and Cytochemistry, 2011, 20(3): 203-206. (in Chinese)
李健, 郝钰, 张玉丽, 等. 小檗碱对CT26皮下移植瘤组织中肿瘤相关巨噬细胞的影响［J］.中国组织化学与细胞化学杂志,2011,20(3): 203-206.
［13］Su DM, Zhu-Ge L, Li J, et al. A mouse model of nonalcoholic steatohepatitis induced by feeding a methionine-choline-deficient diet: establishment and dynamic monitoring ［J］. World Chinese Journal of Digestology, 2011, 19 (11): 1122-1127. (in Chinese)
苏冬梅,诸葛丽,李健,等. 蛋氨酸-胆碱缺乏饮食诱导的非酒精性脂肪性肝炎小鼠模型的建立及动态监测［J］. 世界华人消化杂志, 2011,19(11): 1122-1127.
［14］Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease ［J］. Hepatology, 2005, 41(6): 1313-1321.
［15］Jerrold MO, Christopher KG. Macrophages, inflammation and insulin resistance ［J］. Annu. Rev. Physiol, 2010, 72(1): 219-246.
［16］Zhang YT, An W. Role of liver innate immune cells in nonalcoholic fatty liver disease［J］. World J Gastroeuterol, 2010, 16 (37): 4652-4660.
［17］Oh DY, Morinaga H, Talukdar S, et al. Increased macrophage migration into adipose tissue in obese mice［J］. Diabetes, 2012, 61(2): 346-354.
［18］Chawla A. Control of macrophage activation and function by PPARs ［J］. Circ Res, 2010, 106(10): 1559-1569.
［19］Odegaard JI, Ricardo-Gonzalez RR, Goforth MH, et al. Macrophage-specific PPARγ controls alternative activation and improves insulin resistance［J］. Nature, 2007, 447 (7148): 1116-1120.
［20］Younossi ZM. Review article: current management of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis［J］. Aliment Pharmacol Ther, 2008, 28 (1) : 2-12.
［21］Jeong HW, Hsu KC, Lee JW, et al. Berberine suppresses proinflammatory responses through AMPK activation in macrophages［J］. Am J Physiol Endocrinol Metab, 2009, 296(4): E955-964.
［22］Chen FL, Yang ZH, Liu Y,et al. Berberine inhibits the expression of TNF-αlpha, MCP-1, and IL-6 in AcLDL-stimulated macrophages through PPAR-gamma pathway［J］. Endocrine, 2008, 33(3): 331-337.

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