Chinese herbal medicine in the treatment of nonalcoholic fatty liver disease

Abstract

Chinese herbal medicine has developed new therapies for nonalcoholic fatty liver disease (NAFLD) based on its unique theory system and substantial herb remedies. In this review, 21 traditional Chinese herbs were introduced for their potential benefit in the treatment of NAFLD. Majority of them are evaluated by experimental studies and few by multicenter clinical trials. Herbal monomers as berberine and resveratrol, extracts from Polygonum hypoleucum Ohwi, and Artemisia sacrorum Ledeb., and formulae including Yinchenhao Decoction (茵陈蒿汤, YCHD), Qushi Huayu Decoction (祛湿化瘀汤, QSHYD), and Danning Tablet (胆宁片) were discussed in detail on their therapeutic potentials. Most of these herbal medicines were proved to improve biochemical and histological changes of NAFLD both in vitro and in vivo. Also, their therapeutic activities were associated with inhibiting lipid accumulation through adenosine monophosphate-activated protein kinase activation or upregulating low-density lipoprotein receptor (LDLR) expression, alleviating lipid peroxidation, and reducing the production of inflammatory cytokines. Although the efficacy and safety of these herbal medicines needed to be evaluated in multicenter large-scale clinical trials, Chinese medicine is promising and effective for preventing and treating NAFLD disease.

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References

  1. 1.

    Fan JG, Farrell GC. Epidemiology of non-alcoholic fatty liver disease in China. J Hepatol 2009;50:204–210.

    PubMed  Article  Google Scholar 

  2. 2.

    Angulo P. GI epidemiology: nonalcoholic fatty liver disease. Aliment Pharmacol Ther 2007;25:883–889.

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Williams R. Global challenges in liver disease. Hepatology 2006;44:521–526.

    PubMed  Article  Google Scholar 

  4. 4.

    Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002;346:1221–1231.

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Sheth SG, Gordon FD, Chopra S. Nonalcoholic steatohepatitis. Ann Intern Med 1997;126:137–145.

    PubMed  CAS  Google Scholar 

  6. 6.

    Wang YX, Wang LT, Gao YQ, Sun XH, Zhang B, He JY, et al. Epidemic survey on TCM syndrome typing and preliminary discussion on TCM etiology and pathogenesis of fatty liver. Chin J Integr Tradit West Med (Chin) 2005;25:126–130.

    CAS  Google Scholar 

  7. 7.

    Wang LT. Thinking on integrative medicine for treatment of non-alcoholic fatty liver disease. Chin J Integr Tradit West Med (Chin) 2009;29:1061–1063.

    Article  Google Scholar 

  8. 8.

    Tang DC. Herbology. Shanghai: Shanghai University of Traditional Chinese Medicine Press; 2006:74.

    Google Scholar 

  9. 9.

    Leng SH, Lu FE, Xu LJ. Therapeutic effects of berberine in impaired glucose tolerance rats and its influence on insulin secretion. Acta Pharmacol Sin 2004;25:496–502.

    PubMed  CAS  Google Scholar 

  10. 10.

    McCullough AJ. Pathophysiology of nonalcoholic steatohepatitis. J Clin Gastroenterol 2006;40:S17–S29.

    PubMed  CAS  Google Scholar 

  11. 11.

    Hardie DG. AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol 2007;8:774–785.

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Kim WS, Lee YS, Cha SH, Jeong HW, Choe SS, Lee MR, et al. Berberine improves lipid dysregulation in obesity by controlling central and peripheral AMPK activity. Am J Physiol Endocrinol Metab 2009;296:E812–E819.

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Zhou JY, Zhou SW, Zhang KB, Tang JL, Guang LX, Ying Y, et al. Chronic effects of berberine on blood, liver glucolipid metabolism and liver PPARs expression in diabetic hyperlipidemic rats. Biol Pharm Bull 2008;31:1169–1176.

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Chang X, Yan H, Fei J, Jiang M, Zhu H, Lu D, et al. Berberine reduces the methylation of the MTTP promoter and alleviates fatty liver induced by a high-fat diet in rats. J Lipid Res 2010;51:2504–2515.

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Wang Y, Campbell T, Perry B, Beaurepaire C, Qin L. Hypoglycemic and insulin-sensitizing effects of berberine in high-fat diet- and streptozotocin-induced diabetic rats. Metabolism 2011;60:298–305.

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Jeong HW, Hsu KC, Lee JW, Ham M, Huh JY, Shin HJ, et al. Berberine suppresses proinflammatory responses through AMPK activation in macrophages. Am J Physiol Endocrinol Metab 2009;296:E955–E964.

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Hsiang CY, Wu SL, Cheng SE, Ho TY. Acetaldehydeinduced interleukin-1beta and tumor necrosis factor-alpha production is inhibited by berberine through nuclear factorkappaB signaling pathway in HepG2 cells. J Biomed Sci 2005;12:791–801.

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Brusq JM, Ancellin N, Grondin P, Guillard R, Martin S, Saintillan Y, et al. Inhibition of lipid synthesis through activation of AMP kinase: an additional mechanism for the hypolipidemic effects of berberine. J Lipid Res 2006;47:1281–1288.

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Kong W, Wei J, Abidi P, Lin M, Inaba S, Li C, et al. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med 2004;10:1344–1351.

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    Abidi P, Zhou Y, Jiang JD, Liu J. Extracellular signalregulated kinase-dependent stabilization of hepatic low-density lipoprotein receptor mRNA by herbal medicine berberine. Arterioscler Thromb Vasc Biol 2005;25:2170–2176.

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Yin J, Gao Z, Liu D, Liu Z, Ye J. Berberine improves glucose metabolism through induction of glycolysis. Am J Physiol Endocrinol Metab 2008;294:E148–E156.

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Lee S, Lim HJ, Park HY, Lee KS, Park JH, Jang Y. Berberine inhibits rat vascular smooth muscle cell proliferation and migration in vitro and improves neointima formation after balloon injury in vivo. Berberine improves neointima formation in a rat model. Atherosclerosis 2006;186:29–37.

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Liang KW, Ting CT, Yin SC, Chen YT, Lin SJ, Liao JK, et al. Berberine suppresses MEK/ERK-dependent Egr-1 signaling pathway and inhibits vascular smooth muscle cell regrowth after in vitro mechanical injury. Biochem Pharmacol 2006;71:806–817.

    PubMed  Article  CAS  Google Scholar 

  24. 24.

    Lee S, Lim HJ, Park JH, Lee KS, Jang Y, Park HY. Berberine-induced LDLR up-regulation involves JNK pathway. Biochem Biophys Res Commun 2007;362:853–857.

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Kong WJ, Wei J, Zuo ZY, Wang YM, Song DQ, You XF, et al. Combination of simvastatin with berberine improves the lipid-lowering efficacy. Metabolism 2008;57:1029–1037.

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    Fan E, Jiang S, Zhang L, Bai Y. Molecular mechanism of apoptosis induction by resveratrol, a natural cancer chemopreventive agent. Int J Vitam Nutr Res 2008;78:3–8.

    PubMed  Article  CAS  Google Scholar 

  27. 27.

    Jiang WJ. Sirtuins: novel targets for metabolic disease in drug development. Biochem Biophys Res Commun 2008;373:341–344.

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Tian WX. Inhibition of fatty acid synthase by polyphenols. Curr Med Chem 2006;13:967–977.

    PubMed  Article  CAS  Google Scholar 

  29. 29.

    Shang J, Chen LL, Xiao FX, Sun H, Ding HC, Xiao H. Resveratrol improves non-alcoholic fatty liver disease by activating AMP-activated protein kinase. Acta Pharmacol Sin 2008;29:698–706.

    PubMed  Article  CAS  Google Scholar 

  30. 30.

    Rivera L, Morón R, Zarzuelo A, Galisteo M. Long-term resveratrol administration reduces metabolic disturbances and lowers blood pressure in obese Zucker rats. Biochem Pharmacol 2009;77:1053–1063.

    PubMed  Article  CAS  Google Scholar 

  31. 31.

    Um JH, Park SJ, Kang H, Yang S, Foretz M, McBurney MW, et al. AMP-activated protein kinase-deficient mice are resistant to the metabolic effects of resveratrol. Diabetes 2010;59:554–563.

    PubMed  Article  CAS  Google Scholar 

  32. 32.

    Aoun M, Michel F, Fouret G, Casas F, Jullien M, Wrutniak-Cabello C, et al. A polyphenol extract modifies quantity but not quality of liver fatty acid content in high-fat-high-sucrose diet-fed rats: possible implication of the sirtuin pathway. Br J Nutr 2010;104:1760–1770.

    PubMed  Article  CAS  Google Scholar 

  33. 33.

    Purushotham A, Schug TT, Xu Q, Surapureddi S, Guo X, Li X. Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. Cell Metab 2009;9:327–338.

    PubMed  Article  CAS  Google Scholar 

  34. 34.

    Wang GL, Fu YC, Xu WC, Feng YQ, Fang SR, Zhou XH. Resveratrol inhibits the expression of SREBP1 in cell model of steatosis via Sirt1-FOXO1 signaling pathway. Biochem Biophys Res Commun 2009;380:644–649.

    PubMed  Article  CAS  Google Scholar 

  35. 35.

    Fullerton MD, Steinberg GR. SIRT1 takes a backseat to AMPK in the regulation of insulin sensitivity by resveratrol. Diabetes 2010;59:551–553.

    PubMed  Article  CAS  Google Scholar 

  36. 36.

    Hou X, Xu S, Maitland-Toolan KA, Sato K, Jiang B, Ido Y, et al. SIRT1 regulates hepatocyte lipid metabolism through activating AMP-activated protein kinase. J Biol Chem 2008;283:20015–20026.

    PubMed  Article  CAS  Google Scholar 

  37. 37.

    Bujanda L, Hijona E, Larzabal M, Beraza M, Aldazabal P, García-Urkia N, et al. Resveratrol inhibits nonalcoholic fatty liver disease in rats. BMC Gastroenterol 2008;9;8:40.

    Article  Google Scholar 

  38. 38.

    Dong H, Lu FE, Gao ZQ, Xu LJ, Wang KF, Zou X. Effects of emodin on treating murine nonalcoholic fatty liver induced by high caloric laboratory chaw. World J Gastroenterol 2005;11:1339–1344.

    PubMed  CAS  Google Scholar 

  39. 39.

    Lin CL, Huang HC, Lin JK. Theaflavins attenuate hepatic lipid accumulation through activating AMPK in human HepG2 cells. J Lipid Res 2007;48:2334–2343.

    PubMed  Article  CAS  Google Scholar 

  40. 40.

    Pan SY, Dong H, Zhao XY, Xiang CJ, Fang HY, Fong WF, et al. Schisandrin B from Schisandra chinensis reduces hepatic lipid contents in hypercholesterolaemic mice. J Pharm Pharmacol 2008;60:399–403.

    PubMed  Article  CAS  Google Scholar 

  41. 41.

    Pan SY, Yang R, Dong H, Yu ZL, Ko KM. Bifendate treatment attenuates hepatic steatosis in cholesterol/bile salt- and high-fat diet-induced hypercholesterolemia in mice. Eur J Pharmacol 2006;552:170–175.

    PubMed  Article  CAS  Google Scholar 

  42. 42.

    Zheng P, Ji G, Ma Z, Liu T, Xin L, Wu H, 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 2009;37:69–83.

    PubMed  Article  CAS  Google Scholar 

  43. 43.

    Kuo YC, Sun CM, Ou JC, Tsai WJ. A tumor cell growth inhibitor from Polygonum hypoleucum Ohwi. Life Sci 1997;61:2335–2344.

    PubMed  Article  CAS  Google Scholar 

  44. 44.

    Chen CH, Chang MY, Lin YS, Lin DG, Chen SW, Chao PM. A herbal extract with acetyl-coenzyme A carboxylase inhibitory activity and its potential for treating metabolic syndrome. Metabolism 2009;58:1297–1305.

    PubMed  Article  CAS  Google Scholar 

  45. 45.

    Mao J, DeMayo FJ, Li H, Abu-Elheiga L, Gu Z, Shaikenov TE, et al. Liver-specific deletion of acetyl-CoA carboxylase 1 reduces hepatic triglyceride accumulation without affecting glucose homeostasis. Proc Natl Acad Sci USA 2006;103:8552–8557.

    PubMed  Article  CAS  Google Scholar 

  46. 46.

    Savage DB, Choi CS, Samuel VT, Liu ZX, Zhang D, Wang A, et al. Reversal of diet-induced hepatic steatosis and hepatic insulin resistance by antisense oligonucleotide inhibitors of acetyl-CoA carboxylases 1 and 2. J Clin Invest 2006;116:817–824.

    PubMed  Article  CAS  Google Scholar 

  47. 47.

    Chao PM, Kuo YH, Lin YS, Chen CH, Chen SW, Kuo YH. The metabolic benefits of Polygonum hypoleucum Ohwi in HepG2 cells and Wistar rats under lipogenic stress. J Agric Food Chem 2010;58:5174–5180.

    PubMed  Article  CAS  Google Scholar 

  48. 48.

    Yuan HD, Yuan HY, Chung SH, Jin GZ, Piao GC. An active part of Artemisia sacrorum Ledeb. attenuates hepatic lipid accumulation through activating AMP-activated protein kinase in human HepG2 cells. Biosci Biotechnol Biochem 2010;74:322–328.

    PubMed  Article  CAS  Google Scholar 

  49. 49.

    Gu X, Xie Z, Wang Q, Liu G, Qu Y, Zhang L, et al. Transcriptome profiling analysis reveals multiple modulatory effects of Ginkgo biloba extract in the liver of rats on a highfat diet. FEBS J 2009;276:1450–1458.

    PubMed  Article  CAS  Google Scholar 

  50. 50.

    Pan SY, Yu ZL, Dong H, Xiang CJ, Fong WF, Ko KM. Ethanol extract of Fructus Schisandrae decreases hepatic triglyceride level in mice fed with a high fat/cholesterol diet, with attention to acute toxicity. Evid Based Complement Alternat Med 2009 Jul 10. [Epub ahead of print].

  51. 51.

    Yan MX, Chen ZY, He BH. Effect of total flavonoids of Chinese hawthorn leaf on expression of NF-κB and its inhibitor in rat liver with non-alcoholic steato-hepatitis. China J Tradit Chin Med Pharm (Chin) 2009;24:139–143.

    CAS  Google Scholar 

  52. 52.

    Hong X, Tang H, Wu L, Li L. Protective effects of the Alisma orientalis extract on the experimental nonalcoholic fatty liver disease. J Pharm Pharmacol 2006;58:1391–1398.

    PubMed  Article  CAS  Google Scholar 

  53. 53.

    Fan XF, Deng YQ, Ye L, Li YD, Chen J, Lu WW, et al. Effect of Xuezhikang Capsule on serum tumor necrosis factor-alpha and interleukin-6 in patients with nonalcoholic fatty liver disease and hyperlipidemia. Chin J Integr Med 2010;16:119–123.

    PubMed  Article  Google Scholar 

  54. 54.

    Lee TY, Chang HH, Lo WC, Lin HC. Alleviation of hepatic oxidative stress by Chinese herbal medicine Yin-Chen-Hao-Tang in obese mice with steatosis. Int J Mol Med 2010;25:837–844.

    PubMed  CAS  Google Scholar 

  55. 55.

    Li HS, Feng Q, Hu YY. Effect of Qushi Huayu Decoction on high-fat diet induced hepatic lipid deposition in rats. Chin J Integr Tradit West Med (Chin) 2009;29:1092–1095.

    Google Scholar 

  56. 56.

    Zhang H, Feng Q, Li HS, Chen SD, Wang XN, Peng JH, et al. Effects of Qushi Huayu Decoction on cathepsin B and tumor necrosis factor-alpha expression in rats with non-alcoholic steatohepatitis. J Chin Integr Med (Chin) 2008;6:928–933.

    Article  CAS  Google Scholar 

  57. 57.

    Li HS, Feng Q, Xu LL, Chen SD, Li XM, Hu YY. Effects of Qushi Huayu Decoction in prevention and treatment of fatty liver in rats based on adiponection-free fatty acid pathway. J Chin Integr Med (Chin) 2009;7:546–551.

    Article  CAS  Google Scholar 

  58. 58.

    Zhang H, Hu YY, Feng Q. Inhibitory effects of Qushi Huayu Decoction on fatty deposition and tumor necrosis factor alpha secretion in HepG2 cells induced by free fatty acid. Chin J Integr Tradit West Med (Chin) 2007;27:1105–1109.

    CAS  Google Scholar 

  59. 59.

    Fan JG. Evaluating the efficacy and safety of Danning Tablets in the short-term treatment of patients with nonalcoholic fatty liver disease: a multicenter clinical trial. Hepatobiliary Pancreat Dis Int 2004;3:375–380.

    PubMed  Google Scholar 

  60. 60.

    Ji G, Fan JG, Chen JJ, Lu LG, Xing LJ, Zheng PY, et al. Effectiveness of Danning Tablet in patients with nonalcoholic fatty liver of damp-heat syndrome type: a multicenter randomized controlled trial. J Chin Integr Med (Chin) 2008;6:128–133.

    Article  Google Scholar 

  61. 61.

    Zhang Q, Zhao Y, Zhang DB, Sun LJ. Effect of Sinai san Decoction on the development of nonalcoholic steatohepatitis in rats. World J Gastroenterol 2005;11:1392–1395.

    PubMed  Google Scholar 

  62. 62.

    Wang N, Dong H, Wei SC, Lu FE. Application of proton magnetic resonance spectroscopy and computerized tomography in the diagnosis and treatment of nonalcoholic fatty Liver disease. J Huazhong Univ Sci Technol Med Sci (Chin) 2008;28:295–298.

    Article  CAS  Google Scholar 

  63. 63.

    Ma Y, Zhao J, Yang S, Jia Y. Cigu Xiaozhi Pills’s influence on lipid peroxidation and TNF-alpha expression in liver tissues of rats with nonalcoholic steatohepatitis. China J Chin Mater Med (Chin) 2010;35:1292–1297.

    Google Scholar 

  64. 64.

    Wang T, Zhang DQ, Li YH, Liu H, Liu ZB, Zhao CF, et al. Regulation effects on abnormal glucose and lipid metabolism of TZQ-F, a new kind of Traditional Chinese Medicine. J Ethnopharmacol 2010;128:575–582.

    Article  Google Scholar 

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Correspondence to Fu-er Lu 陆付耳.

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Supported by the National Natural Science Foundation of China (No. 30772853, 30801492)

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Dong, H., Lu, F. & Zhao, L. Chinese herbal medicine in the treatment of nonalcoholic fatty liver disease. Chin. J. Integr. Med. 18, 152–160 (2012). https://doi.org/10.1007/s11655-012-0993-2

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Keywords

  • nonalcoholic fatty liver disease
  • Chinese herbal medicine