Search JIM Advanced Search

Journal of Integrative Medicine ›› 2014, Vol. 12 ›› Issue (3): 135-146.doi: 10.1016/S2095-4964(14)60023-6

• Review • Previous Articles     Next Articles

Efficacy of polyphenolic ingredients of Chinese herbs in treating dyslipidemia of metabolic syndromes

Zemin Yaoa,b, Li Zhangb, Guang Jib,c   

  1. Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of System Biology, University of Ottawa, Ottawa K1H 8M5, Canada
    Institute of Digestive Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 200032,China
    E-institute of Shanghai Municipal Education Commission, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
  • Received:2013-12-12 Accepted:2014-03-07 Online:2014-05-10 Published:2014-06-26

There is an increasing interest and popularity of Chinese herbal medicine worldwide, which is accompanied by increasing concerns about its effectiveness and potential toxicity. Several ingredients, such as polyphenolic compounds berberine, flavonoids, and curcumin, have been studied extensively by using various animal models. Effectiveness of treatment and amelioration of metabolic syndromes, including insulin resistance and dyslipidemia, has been demonstrated. This review summarizes the major checkpoints and contributing factors in regulation of exogenous and endogenous lipid metabolism, with particular emphasis centered on triglyceride-rich and cholesterol-rich lipoproteins. Available experimental evidence demonstrating the lipid-lowering effect of berberine, flavonoids and curcumin in cell culture and animal models is compiled, and the strengths and shortcomings of experimental designs in these studies are discussed.

Key words: Drugs, Chinese herbal, Metabolic syndromes, Dyslipidemias, Reviews

Figure 1

Schematic representation of exogenous (A) and endogenous (B) lipid metabolism in humans The exogenous lipid metabolism encompasses the process of (i) lipid (e.g., cholesterol) absorption by enterocytes (mediated by ABCG5/8 and NPC1L1), (ii) formation of ApoB-48-containing chylomicrons, (iii) hydrolysis catalyzed by LPL (in complex with GPIHBP1), (iv) utilization of free fatty acids by muscle or adipocytes, and (v) uptake of chylomicron remnants by the liver (through LRP1-mediated endocytosis). The endogenous lipid metabolism includes (i) assembly and secretion of ApoB-100-containing VLDL (facilitated by MTP and ApoC3 in the liver), (ii) conversion of VLDL into remnants and eventually into LDL through the action of LPL and HL, (iii) utilization of free fatty acids, and (iv) clearance of LDL through LDLR-mediated endocytosis by the liver and peripheral tissues (e.g., steroidogenic cells). Formation of HDL and its metabolism are not shown. A-I: apolipoprotein A-I; A-IV: apolipoprotein A-IV; B100: apolipoprotein B-100; B48: apolipoprotein B-48; ABCG5/8: ATP-binding cassette transporter G5 and G8; Cs: apolipoprotein Cs; E: apolipoprotein E; FFA: free fatty acids; GPIHBP1: glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1; HL: hepatic lipase; LDL: low-density lipoprotein; LDLR: low-density lipoprotein receptor; LPL: lipoprotein lipase; LRP1: low-density lipoprotein receptor-related protein 1; MTP: microsomal triglyceride-transfer protein; NPC1L1: Niemann-Pick C1-like 1; VLDL: very-low-density lipoprotein."

Figure 2

Potential targets of the effective ingredients of Chinese herbal medicine in lipoprotein metabolismMajor pathways responsible for fatty acid, triglyceride and cholesterol metabolism are depicted, and protein/lipid factors lipoprotein assembly and secretion are shown. Proteins whose level of expression can be affected by berberine and curcumin treatment are shown (in red). For simplicity, signaling pathways and molecules regulating the expression of these protein/lipid factors are omitted."


[1] Graham MJ, Lee RG , Bell TA 3rd, Fu W, Mullick AE, Alexander VJ, Singleton W, Viney N, Geary R, Su J, Baker BF, Burkey J, Crooke ST, Crooke RM.Antisense oligonucleotide inhibition of apolipoprotein C-III reduces plasma triglycerides in rodents, nonhuman primates, and humans[J]. Circ Res, 2013,112(11):1479-1490
doi: 10.1161/CIRCRESAHA.111.300367
[2] Hewing B, Parathath S, Mai CK, Fiel MI, Guo L, Fisher EA . Rapid regression of atherosclerosis with MTP inhibitor treatment[J]. Atherosclerosis, 2013,227(1):125-129
doi: 10.1016/j.atherosclerosis.2012.12.026
[3] Hussain MM, Rava P, Pan X, Dai K, Dougan SK, Iqbal J, Lazare F, Khatun I . Microsomal triglyceride transfer protein in plasma and cellular lipid metabolism[J]. Curr Opin Lipidol, 2008,19(3):277-284
doi: 10.1097/MOL.0b013e3282feea85
[4] Aegerion Pharmaceuticals , Inc. FDA approves Aegerion Pharmaceuticals’ JUXTAPIDTM (lomitapide) Capsules for homozygous familial hypercholesterolemia (HoFH). (2012-12-24)[ 2013-6-15]. .
[5] Sundaram M, Yao Z . Intrahepatic role of exchangeable apolipoproteins in lipoprotein assembly and secretion[J]. Arterioscler Thromb Vasc Biol, 2012,32(5):1073-1078
doi: 10.1161/ATVBAHA.111.241455
[6] Yao Z, Wang Y . Apolipoprotein C-III and hepatic triglyceride-rich lipoprotein production[J]. Curr Opin Lipidol, 2012,23(3):206-212
doi: 10.1097/MOL.0b013e328352dc70
[7] Furtado JD, Wedel MK, Sacks FM . Antisense inhibition of apoB synjournal with mipomersen reduces plasma apoC-III and apoC-III-containing lipoproteins[J]. J Lipid Res, 2012,53(4):784-791
doi: 10.1194/jlr.P021717
[8] Samaha FF , McKenney J, Bloedon LT, Sasiela WJ, Rader DJ.Inhibition of microsomal triglyceride transfer protein alone or with ezetimibe in patients with moderate hypercholesterolemia[J]. Nat Clin Pract Cardiovasc Med, 2008,5(8):497-505
doi: 10.1038/ncpcardio1250
[9] Goldstein JL, Brown MS . The LDL receptor[J]. Arterioscler Thromb Vasc Biol, 2009,29(4):431-438
doi: 10.1161/ATVBAHA.108.179564
[10] Brown MS, Goldstein JL . Cholesterol feedback: from Schoenheimer’s bottle to Scap’s MELADL[J]. J Lipid Res, 2009,50(Suppl):S15-S27
doi: 10.1194/jlr.R800054-JLR200
[11] Park SW, Moon YA, Horton JD . Post-transcriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin/kexin type 9a in mouse liver[J]. J Biol Chem, 2004,279(48):50630-50638
doi: 10.1074/jbc.M410077200
[12] Peterson AS, Fong LG, Young SG . PCSK9 function and physiology[J]. J Lipid Res, 2008,49(6):1152-1156
doi: 10.1194/jlr.E800008-JLR200
[13] Steinberg D, Witztum JL . Inhibition of PCSK9: a powerful weapon for achieving ideal LDL cholesterol levels[J]. Proc Natl Acad Sci U S A, 2009,106(24):9546-9547
doi: 10.1073/pnas.0904560106
[14] Timmins JM, Lee JY, Boudyguina E, Kluckman KD, Brunham LR, Mulya A, Gebre AK, Coutinho JM, Colvin PL, Smith TL, Hayden MR, Maeda N, Parks JS . Targeted inactivation of hepatic Abca1 causes profound hypoalphalipoproteinemia and kidney hypercatabolism of apoA-I[J]. J Clin Invest, 2005,115(5):1333-1342
doi: 10.1172/JCI200523915
[15] Wang X, Collins HL, Ranalletta M, Fuki IV, Billheimer JT, Rothblat GH, Tall AR, Rader DJ . Macrophage ABCA1 and ABCG1, but not SR-BI, promote macrophage reverse cholesterol transport in vivo[J]. J Clin Invest, 2007,117(8):2216-2224
doi: 10.1172/JCI32057
[16] Brooks R, Jennions MD . The dark side of sexual selection[J]. Trends Ecol Evol, 1999,14(9):336-337
doi: 10.1016/S0169-5347(99)01689-4
[17] Orso E, Broccardo C, Kaminski WE, Bottcher A, Liebisch G, Drobnik W, Gotz A, Chambenoit O, Diederich W, Langmann T, Spruss T, Luciani MF, Rothe G, Lackner KJ, Chimini G, Schmitz G . Transport of lipids from Golgi to plasma membrane is defective in tangier disease patients and Abc1-deficient mice[J]. Nat Genet, 2000,24(2):192-196
doi: 10.1038/72869
[18] Knox R. Merck: niacin drug mix fails to prevent heart attacks, strokes. (2012-12-20)[ 2013-6-20]. .
[19] Klett EL, Patel S . Genetic defenses against noncholesterol sterols[J]. Curr Opin Lipidol, 2003,14(4):341-345
doi: 10.1097/00041433-200308000-00001
[20] Altmann SW, Davis HR Jr., Zhu LJ, Yao X, Hoos LM, Tetzloff G, Iyer SP, Maguire M, Golovko A, Zeng M, Wang L, Murgolo N, Graziano MP . Niemann-Pick C1 like 1 protein is critical for intestinal cholesterol absorption[J]. Science, 2004,303(5661):1201-1204
doi: 10.1126/science.1093131
[21] Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, Crona JH, Davis HR Jr., Dean DC, Detmers PA, Graziano MP, Hughes M, Macintyre DE, Ogawa A , O’Neill K A, Iyer SP, Shevell DE, Smith MM, Tang YS, Makarewicz AM, Ujjainwalla F, Altmann SW, Chapman KT, Thornberry NA. The target of ezetimibe is Niemann-Pick C1-like 1(NPC1L1)[J]. Proc Natl Acad Sci U S A, 2005,102(23):8132-8137
doi: 10.1073/pnas.0500269102
[22] Grigore L, Norata GD, Catapano AL . Combination therapy in cholesterol reduction: focus on ezetimibe and statins[J]. Vasc Health Risk Manag, 2008,4(2):267-278
doi: 10.2147/VHRM
[23] Burnett JR, Watts GF . MTP inhibition as a treatment for dyslipidemias: time to deliver or empty promises? Expert Opin Ther Targets. 2007; 11(2):181-189.
doi: 10.1517/14728222.11.2.181
[24] Hesse D, Radloff K, Jaschke A, Lagerpusch M, Chung B, Tailleux A, Staels B, Schurmann A . Hepatic trans-Golgi action coordinated by the GTPase ARFRP1 is crucial for lipoprotein lipidation and assembly[J]. J Lipid Res, 2014,55(1):41-52
doi: 10.1194/jlr.M040089
[25] Jones B, Jones EL, Bonney SA, Patel HN, Mensenkamp AR, Eichenbaum-Voline S, Rudling M, Myrdal U, Annesi G, Naik S, Meadows N, Quattrone A, Islam SA, Naoumova RP, Angelin B, Infante R, Levy E, Roy CC, Freemont PS, Scott J, Shoulders CC . Mutations in a Sar1 GTPase of COPII vesicles are associated with lipid absorption disorders[J]. Nat Genet, 2003,34(1):29-31
doi: 10.1038/ng1145
[26] Young SG, Davies BS, Voss CV, Gin P, Weinstein MM, Tontonoz P, Reue K, Bensadoun A, Fong LG, Beigneux AP . GPIHBP1, an endothelial cell transporter for lipoprotein lipase[J]. J Lipid Res, 2011,52(11):1869-1884
doi: 10.1194/jlr.R018689
[27] Brunzell JD, Deeb S. Familial lipoprotein lipase deficiency, apoCII deficiency, and hepatic lipase deficiency. In: Scriver CR, Beaudet AL, Sly WS, Valle D. The metabolic and molecular bases of inherited disease.8th ed[M]. New York: McGraw-Hill Medical Publishing Division, 2001: 2789-2816
[28] Sundaram M, Yao Z . Recent progress in understanding protein and lipid factors affecting hepatic VLDL assembly and secretion[J]. Nutr Metab (Lond), 2010,7:35
doi: 10.1186/1743-7075-7-35
[29] Adiels M, Borén J, Caslake MJ, Stewart P, Soro A, Westerbacka J, Wennberg B, Olofsson SO, Packard C, Taskinen MR . Overproduction of VLDL1 driven by hyperglycemia is a dominant feature of diabetic dyslipidemia[J]. Arterioscler Thromb Vasc Biol, 2005,25(8):1697-1703
doi: 10.1161/01.ATV.0000172689.53992.25
[30] Gill JM, Brown JC, Bedford D, Wright DM, Cooney J, Hughes DA, Packard CJ, Caslake MJ . Hepatic production of VLDL1 but not VLDL2 is related to insulin resistance in normoglycaemic middle-aged subjects[J]. Atherosclerosis, 2004,176(1):49-56
doi: 10.1016/j.atherosclerosis.2004.04.022
[31] Wu X, Chen K, Williams KJ . The role of pathway-selective insulin resistance and responsiveness in diabetic dyslipoproteinemia[J]. Curr Opin Lipidol, 2012,23(4):334-344
doi: 10.1097/MOL.0b013e3283544424
[32] Lafontan M, Langin D . Lipolysis and lipid mobilization in human adipose tissue[J]. Prog Lipid Res, 2009,48(5):275-297
doi: 10.1016/j.plipres.2009.05.001
[33] Jiang ZG, Robson SC, Yao Z . Lipoprotein metabolism in nonalcoholic fatty liver disease[J]. J Biomed Res, 2013,27(1):1-13
[34] Yao Z, Zhou H, Figeys D, Wang Y, Sundaram M . Microsome-associated lumenal lipid droplets in the regulation of lipoprotein secretion[J]. Curr Opin Lipidol, 2013,24(2):160-170
doi: 10.1097/MOL.0b013e32835aebe7
[35] Myers MG Jr., Heymsfield SB, Haft C, Kahn BB, Laughlin M, Leibel RL, Tschop MH, Yanovski JA . Challenges and opportunities of defining clinical leptin resistance[J]. Cell Metab, 2012,15(2):150-156
doi: 10.1016/j.cmet.2012.01.002
[36] L?llmann B, Grüninger S, Stricker-Krongrad A, Chiesi M . Detection and quantification of the leptin receptor splice variants Ob-Ra, b, and, e in different mouse tissues[J]. Biochem Biophys Res Commun, 1997,238(2):648-652
doi: 10.1006/bbrc.1997.7205
[37] Choi SM, Tucker DF, Gross DN, Easton RM , DiPilato LM, Dean AS, Monks BR, Birnbaum MJ.Insulin regulates adipocyte lipolysis via an Akt-independent signaling pathway[J]. Mol Cell Biol, 2010,30(21):5009-5020
doi: 10.1128/MCB.00797-10
[38] Brown MS, Goldstein JL . Selective versus total insulin resistance: a pathogenic paradox[J]. Cell Metab, 2008,7(2):95-96
doi: 10.1016/j.cmet.2007.12.009
[39] Kamagate A, Qu S, Perdomo G, Su D, Kim DH, Slusher S, Meseck M, Dong HH . FoxO1 mediates insulin-dependent regulation of hepatic VLDL production in mice[J]. J Clin Invest, 2008,118(6):2347-2364
[40] Altomonte J, Cong L, Harbaran S, Richter A, Xu J, Meseck M, Dong HH . Foxo1 mediates insulin action on apoC-III and triglyceride metabolism[J]. J Clin Invest, 2004,114(10):1493-1503
doi: 10.1172/JCI200419992
[41] Phung TL, Roncone A, Jensen KL, Sparks CE, Sparks JD . Phosphoinositide 3-kinase activity is necessary for insulin-dependent inhibition of apolipoprotein B secretion by rat hepatocytes and localizes to the endoplasmic reticulum[J]. J Biol Chem, 1997,272(49):30693-30702
doi: 10.1074/jbc.272.49.30693
[42] Carvalheira JB, Torsoni MA, Ueno M, Amaral ME, Araujo EP, Velloso LA, Gontijo JA, Saad MJ . Cross-talk between the insulin and leptin signaling systems in rat hypothalamus[J]. Obes Res, 2005,13(1):48-57
doi: 10.1038/oby.2005.7
[43] Andrews RC, Walker BR . Glucocorticoids and insulin resistance: old hormones, new targets[J]. Clin Sci (Lond), 1999,96(5):513-523
doi: 10.1042/cs0960513
[44] Masuzaki H, Paterson J, Shinyama H, Morton NM, Mullins JJ, Seckl JR, Flier JS . A transgenic model of visceral obesity and the metabolic syndrome[J]. Science, 2001,294(5549):2166-2170
doi: 10.1126/science.1066285
[45] Guinane CM, Cotter PD . Role of the gut microbiota in health and chronic gastrointestinal disease: understanding a hidden metabolic organ[J]. Therap Adv Gastroenterol, 2013,6(4):295-308
doi: 10.1177/1756283X13482996
[46] Lee YS, Kim WS, Kim KH, Yoon MJ, Cho HJ, Shen Y, Ye JM, Lee CH, Oh WK, Kim CT, Hohnen-Behrens C, Gosby A, Kraegen EW, James DE, Kim JB . Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states[J]. Diabetes, 2006,55(8):2256-2264
doi: 10.2337/db06-0006
[47] Kim WS, Lee YS, Cha SH, Jeong HW, Choe SS, Lee MR, Oh GT, Park HS, Lee KU, Lane MD, Kim JB . Berberine improves lipid dysregulation in obesity by controlling central and peripheral AMPK activity[J]. Am J Physiol Endocrinol Metab, 2009,296(4):E812-E819
doi: 10.1152/ajpendo.90710.2008
[48] Chang XX, Yan HM, Xu Q, Xia MF, Bian H, Zhu TF, Gao X . The effects of berberine on hyperhomocysteinemia and hyperlipidemia in rats fed with a long-term high-fat diet[J]. Lipids Health Dis, 2012,11:86
doi: 10.1186/1476-511X-11-86
[49] Hu Y, Davies GE . Berberine inhibits adipogenesis in high-fat diet-induced obesity mice[J]. Fitoterapia, 2010,81(5):358-366
doi: 10.1016/j.fitote.2009.10.010
[50] Kong W, Wei J, Abidi P, Lin M, Inaba S, Li C, Wang Y, Wang Z, Si S, Pan H, Wang S, Wu J, Li Z, Liu J, Jiang JD . Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins[J]. Nat Med, 2004,10(12):1344-1351
doi: 10.1038/nm1135
[51] Zhou JY, Zhou SW, Zhang KB, Tang JL, Guang LX, Ying Y, Xu Y, Zhang L, Li DD . Chronic effects of berberine on blood, liver glucolipid metabolism and liver PPARs expression in diabetic hyperlipidemic rats[J]. Biol Pharm Bull, 2008,31(6):1169-1176
doi: 10.1248/bpb.31.1169
[52] Wu N, Sarna LK, Siow YL , O K.Regulation of hepatic cholesterol biosynjournal by berberine during hyperhomocysteinemia[J]. Am J Physiol Regul Integr Comp Physiol, 2011,300(3):R635-R643
doi: 10.1152/ajpregu.00441.2010
[53] Yin J, Xing H, Ye J . Efficacy of berberine in patients with type 2 diabetes mellitus[J]. Metabolism, 2008,57(5):712-717
doi: 10.1016/j.metabol.2008.01.013
[54] Zhang Y, Li X, Zou D, Liu W, Yang J, Zhu N, Huo L, Wang M, Hong J, Wu P, Ren G, Ning G . Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine[J]. J Clin Endocrinol Metab, 2008,93(7):2559-2565
doi: 10.1210/jc.2007-2404
[55] Zhang H, Wei J, Xue R, Wu JD, Zhao W, Wang ZZ, Wang SK, Zhou ZX, Song DQ, Wang YM, Pan HN, Kong WJ, Jiang JD . Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression[J]. Metabolism, 2010,59(2):285-292
doi: 10.1016/j.metabol.2009.07.029
[56] Derosa G , D’Angelo A, Bonaventura A, Bianchi L, Romano D, Maffioli P.Effects of berberine on lipid profile in subjects with low cardiovascular risk[J]. Expert Opin Biol Ther, 2013,13(4):475-482
doi: 10.1517/14712598.2013.776037
[57] Trimarco B, Benvenuti C, Rozza F, Cimmino CS, Giudice R, Crispo S . Clinical evidence of efficacy of red yeast rice and berberine in a large controlled study versus diet[J]. Med J Nutrition Metab, 2011,4(2):133-139
doi: 10.1007/s12349-010-0043-6
[58] Ge Y, Zhang Y, Li R, Chen W, Li Y, Chen G . Berberine regulated Gck, G6pc, Pck1 and Srebp-1c expression and activated AMP-activated protein kinase in primary rat hepatocytes[J]. Int J Biol Sci, 2011,7(5):673-684
doi: 10.7150/ijbs.7.673
[59] Zhao HL, Sui Y, Qiao CF, Yip KY, Leung RK, Tsui SK, Lee HM, Wong HK, Zhu X, Siu JJ, He L, Guan J, Liu LZ, Xu HX, Tong PC, Chan JC . Sustained antidiabetic effects of a berberine-containing Chinese herbal medicine through regulation of hepatic gene expression[J]. Diabetes, 2012,61(4):933-943
doi: 10.2337/db11-1164
[60] Zhou J, Zhou S . Berberine regulates peroxisome proliferator-activated receptors and positive transcription elongation factor b expression in diabetic adipocytes[J]. Eur J Pharmacol, 2010,649(1-3):390-397
doi: 10.1016/j.ejphar.2010.09.030
[61] Li H, Dong B, Park SW, Lee HS, Chen W, Liu J . Hepatocyte nuclear factor 1α plays a critical role in PCSK9 gene transcription and regulation by the natural hypocholesterolemic compound berberine[J]. J Biol Chem, 2009,284(42):28885-28895
doi: 10.1074/jbc.M109.052407
[62] Abidi P, Zhou Y, Jiang JD, Liu J . Extracellular signal-regulated kinase-dependent stabilization of hepatic low-density lipoprotein receptor mRNA by herbal medicine berberine[J]. Arterioscler Thromb Vasc Biol, 2005,25(10):2170-2176
doi: 10.1161/01.ATV.0000181761.16341.2b
[63] Lee TS, Pan CC, Peng CC, Kou YR, Chen CY, Ching LC, Tsai TH, Chen SF, Lyu PC, Shyue SK . Anti-atherogenic effect of berberine on LXRα-ABCA1-dependent cholesterol efflux in macrophages[J]. J Cell Biochem, 2010,111(1):104-110
doi: 10.1002/jcb.22667
[64] Li GS, Liu XH, Zhu H, Huang L, Liu YL, Ma CM, Qin C . Berberine-improved visceral white adipose tissue insulin resistance associated with altered sterol regulatory element-binding proteins, liver X receptors, and peroxisome proliferator-activated receptors transcriptional programs in diabetic hamsters[J]. Biol Pharm Bull, 2011,34(5):644-654
doi: 10.1248/bpb.34.644
[65] Chen C, Zhang Y, Huang C . Berberine inhibits PTP1B activity and mimics insulin action[J]. Biochem Biophys Res Commun, 2010,397(3):543-547
doi: 10.1016/j.bbrc.2010.05.153
[66] Cheng Z, Pang T, Gu M, Gao AH, Xie CM, Li JY, Nan FJ, Li J . Berberine-stimulated glucose uptake in L6 myotubes involves both AMPK and p38 MAPK[J]. Biochim Biophys Acta, 2006,1760(11):1682-1689
doi: 10.1016/j.bbagen.2006.09.007
[67] Chang X, Yan H, Fei J, Jiang M, Zhu H, Lu D, Gao X . Berberine reduces methylation of the MTTP promoter and alleviates fatty liver induced by a high-fat diet in rats[J]. J Lipid Res, 2010,51(9):2504-2515
doi: 10.1194/jlr.M001958
[68] Zhou Y, Cao S, Wang Y, Xu P, Jian K, Bin W, Qiu F, Kang N . Berberine metabolites could induce low density lipoprotein receptor up-regulation to exert lipid-lowering effects in human hepatoma cells[J]. Fitoterapia, 2014,92:230-237
doi: 10.1016/j.fitote.2013.11.010
[69] Xie W, Gu D, Li J, Cui K, Zhang Y . Effects and action mechanisms of berberine and Rhizoma coptidis on gut microbes and obesity in high-fat diet-fed C57BL/6J mice[J]. PLoS One, 2011,6(9):e24520
doi: 10.1371/journal.pone.0024520
[70] Zhang X, Zhao Y, Zhang M, Pang X, Xu J, Kang C, Li M, Zhang C, Zhang Z, Zhang Y, Li X, Ning G, Zhao L . Structural changes of gut microbiota during berberine-mediated prevention of obesity and insulin resistance in high-fat diet-fed rats[J]. PLoS One, 2012,7(8):e42529
doi: 10.1371/journal.pone.0042529
[71] Koo SI, Noh SK . Green tea as inhibitor of the intestinal absorption of lipids: potential mechanism for its lipid-lowering effect[J]. J Nutr Biochem, 2007,18(3):179-183
doi: 10.1016/j.jnutbio.2006.12.005
[72] Hayek T, Fuhrman B, Vaya J, Rosenblat M, Belinky P, Coleman R, Elis A, Aviram M . Reduced progression of atherosclerosis in apolipoprotein E-deficient mice following consumption of red wine, or its polyphenols quercetin or catechin, is associated with reduced susceptibility of LDL to oxidation and aggregation[J]. Arterioscler Thromb Vasc Biol, 1997,17(11):2744-2752
doi: 10.1161/01.ATV.17.11.2744
[73] Allister EM, Borradaile NM, Edwards JY, Huff MW . Inhibition of microsomal triglyceride transfer protein expression and apolipoprotein B100 secretion by the citrus flavonoid naringenin and by insulin involves activation of the mitogen-activated protein kinase pathway in hepatocytes[J]. Diabetes, 2005,54(6):1676-1683
doi: 10.2337/diabetes.54.6.1676
[74] Borradaile NM, de Dreu LE, Huff MW . Inhibition of net HepG2 cell apolipoprotein B secretion by the citrus flavonoid naringenin involves activation of phosphatidylinositol 3-kinase, independent of insulin receptor substrate-1 phosphorylation[J]. Diabetes, 2003,52(10):2554-2561
doi: 10.2337/diabetes.52.10.2554
[75] Mulvihill EE, Allister EM, Sutherland BG, Telford DE, Sawyez CG, Edwards JY, Markle JM, Hegele RA, Huff MW . Naringenin prevents dyslipidemia, apolipoprotein B overproduction, and hyperinsulinemia in LDL receptor-null mice with diet-induced insulin resistance[J]. Diabetes, 2009,58(10):2198-2210
doi: 10.2337/db09-0634
[76] Nahmias Y, Goldwasser J , Casali M, van Poll D, Wakita T, Chung RT, Yarmush ML.Apolipoprotein B-dependent hepatitis C virus secretion is inhibited by the grapefruit flavonoid naringenin[J]. Hepatology, 2008,47(5):1437-1445
doi: 10.1002/hep.22197
[77] Casaschi A, Wang Q, Dang K, Richards A, Theriault A . Intestinal apolipoprotein B secretion is inhibited by the flavonoid quercetin: potential role of microsomal triglyceride transfer protein and diacylglycerol acyltransferase[J]. Lipids, 2002,37(7):647-652
doi: 10.1007/s11745-002-0945-8
[78] Kurowska EM, Manthey JA, Casaschi A, Theriault AG . Modulation of HepG2 cell net apolipoprotein B secretion by the citrus polymethoxyflavone, tangeretin[J]. Lipids, 2004,39(2):143-151
doi: 10.1007/s11745-004-1212-8
[79] Jang EM, Choi MS, Jung UJ, Kim MJ, Kim HJ, Jeon SM, Shin SK, Seong CN, Lee MK . Beneficial effects of curcumin on hyperlipidemia and insulin resistance in high-fat-fed hamsters[J]. Metabolism, 2008,57(11):1576-1583
doi: 10.1016/j.metabol.2008.06.014
[80] Seo KI, Choi MS, Jung UJ, Kim HJ, Yeo J, Jeon SM, Lee MK . Effect of curcumin supplementation on blood glucose, plasma insulin, and glucose homeostasis related enzyme activities in diabetic db/db mice[J]. Mol Nutr Food Res, 2008,52(9):995-1004
doi: 10.1002/mnfr.v52:9
[81] Li JM, Li YC, Kong LD, Hu QH . Curcumin inhibits hepatic protein-tyrosine phosphatase 1B and prevents hypertriglyceridemia and hepatic steatosis in fructose-fed rats[J]. Hepatology, 2010,51(5):1555-1566
doi: 10.1002/hep.23524
[82] Kang OH, Kim SB, Seo YS, Joung DK, Mun SH, Choi JG, Lee YM, Kang DG, Lee HS, Kwon DY . Curcumin decreases oleic acid-induced lipid accumulation via AMPK phosphorylation in hepatocarcinoma cells[J]. Eur Rev Med Pharmacol Sci, 2013,17(19):2578-2586
[83] Kim M, Kim Y . Hypocholesterolemic effects of curcumin via up-regulation of cholesterol 7a-hydroxylase in rats fed a high fat diet[J]. Nutr Res Pract, 2010,4(3):191-195
doi: 10.4162/nrp.2010.4.3.191
[84] Manjunatha H, Srinivasan K . Hypolipidemic and antioxidant effects of dietary curcumin and capsaicin in induced hypercholesterolemic rats[J]. Lipids, 2007,42(12):1133-1142
doi: 10.1007/s11745-007-3120-y
[85] Martínez-Morúa A1, Soto-Urquieta MG, Franco-Robles E, Zú?iga-Trujillo I, Campos-Cervantes A, Pérez-Vázquez V, Ramírez-Emiliano J . Curcumin decreases oxidative stress in mitochondria isolated from liver and kidneys of high-fat diet-induced obese mice[J]. J Asian Nat Prod Res, 2013,15(8):905-915
doi: 10.1080/10286020.2013.802687
[86] Hu GX, Lin H, Lian QQ, Zhou SH, Guo J, Zhou HY, Chu Y, Ge RS . Curcumin as a potent and selective inhibitor of 11β-hydroxysteroid dehydrogenase 1: improving lipid profiles in high-fat-diet-treated rats[J]. PLoS One, 2013,8(3):e49976
doi: 10.1371/journal.pone.0049976
[87] Alwi I, Santoso T, Suyono S, Sutrisna B, Suyatna FD, Kresno SB, Ernie S . The effect of curcumin on lipid level in patients with acute coronary syndrome[J]. Acta Med Indones, 2008,40(4):201-210
[88] Gupta SC, Patchva S, Aggarwal BB . Therapeutic roles of curcumin: lessons learned from clinical trials[J]. AAPS J, 2013,15(1):195-218
doi: 10.1208/s12248-012-9432-8
[89] Sahebkar A. A systematic review and meta-analysis of randomized controlled trials investigating the effects of curcumin on blood lipid levels. Clin Nutr. 2013 Sep 25.Epub ahead of print.
[1] Shu-yi Chen, Qun-wei Chen, Liu-mei Shou, Hong Pan, Shan-ming Ruan, Zhe-hao Liang, Qi-jin Shu. Stevens-Johnson syndrome/toxic epidermal necrolysis successfully treated with Chinese herbal medicine Pi-Yan-Ning: A case report. Journal of Integrative Medicine, 2021, 19(6): 555-560.
[2] Xin Yin, Shu-bin Cai, Lan-ting Tao, Lu-ming Chen, Zhong-de Zhang, Su-hong Xiao, Arthur Yin Fan, Xu Zou. Recovery of a patient with severe COVID-19 by acupuncture and Chinese herbal medicine adjuvant to standard care. Journal of Integrative Medicine, 2021, 19(5): 460-466.
[3] Qing-lan Wang, Yan-yan Tao, Hong-dong Xie, Cheng-hai Liu, Ping Liu. Fuzheng Huayu recipe, a traditional Chinese compound herbal medicine, attenuates renal interstitial fibrosis via targeting the miR-21/PTEN/AKT axis. Journal of Integrative Medicine, 2020, 18(6): 505-513.
[4] Ming-sheng Lyu, De-ying Li, Shao-zhong Zhou, Cheng-jun Ban, Jun Yan. Adult-onset Still's disease successfully treated with Chinese herbal medicine: A case report with 15-month follow-up. Journal of Integrative Medicine, 2020, 18(6): 530-534.
[5] Arthur Yin Fan, Sherman Gu, Sarah Faggert Alemi, Research Group for Evidence-based Chinese Medicine. Chinese herbal medicine for COVID-19: Current evidence with systematic review and meta-analysis. Journal of Integrative Medicine, 2020, 18(5): 385-394.
[6] Bin Lan, Jin-wen Ge, Shao-wu Cheng, Xi-long Zheng, Jun Liao, Chao He, Zheng-qing Rao, Guo-zuo Wang. Extract of Naotaifang, a compound Chinese herbal medicine, protects neuron ferroptosis induced by acute cerebral ischemia in rats. Journal of Integrative Medicine, 2020, 18(4): 344-350.
[7] Deng-hai Zhang, Kun-lun Wu, Xue Zhang, Sheng-qiong Deng, Bin Peng. In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus. Journal of Integrative Medicine, 2020, 18(2): 152-158.
[8] Carola Analía Torres, Cristina Marisel Pérez Zamora, María Beatriz Nuñez, Ana María Gonzalez. In vitro antioxidant, antilipoxygenase and antimicrobial activities of extracts from seven climbing plants belonging to the Bignoniaceae. Journal of Integrative Medicine, 2018, 16(4): 255-262.
[9] Zahra Hajmohammadi, Mojtaba Heydari, Majid Nimrouzi, Pouya Faridi, Mohammad Javad Zibaeenezhad, Gholamhossein Ranjbar Omrani, Mesbah Shams . Rhus coriaria L. increases serum apolipoprotein-A1 and high-density lipoprotein cholesterol levels: A double-blind placebo-controlled randomized clinical trial. Journal of Integrative Medicine, 2018, 16(1): 45-50.
[10] Shui-jie Shen, Yong-hong Zhang, Xiao-xia Gu, Shui-ju Jiang, Ling-jun Xu. Yangfei Kongliu Formula, a compound Chinese herbal medicine, combined with cisplatin, inhibits growth of lung cancer cells through transforming growth factor-β1 signaling pathway. Journal of Integrative Medicine, 2017, 15(3): 242-251.
[11] Liliana Zazueta-Beltrán, Lorena Medina-Aymerich, Nadia Estela Díaz-Triste, Aracely Evangelina Chávez-Piña, Gilberto Castañeda-Hernández, Leticia Cruz-Antonio. Evidence against the participation of a pharmacokinetic interaction in the protective effect of single-dose curcumin against gastrointestinal damage induced by indomethacin in rats. Journal of Integrative Medicine, 2017, 15(2): 151-157.
[12] Tom Fleischer, Tung-Ti Chang, Hung-Rong Yen. Post-hematopoietic stem cell transplantation in patients with hematologic disorders: Chinese herbal medicine for an unmet need. Journal of Integrative Medicine, 2016, 14(5): 322-335.
[13] JiaXia, Li-qunHe, XiaoSu. Interventional mechanisms of herbs or herbal extracts on renal interstitial fibrosis. Journal of Integrative Medicine, 2016, 14(3): 165-173.
[14] Mojtaba Heydari, Mohammad Hashem Hashempur, Mohammad Hosein Ayati, Detlev Quintern, Majid Nimrouzi, Seyed Hamdollah Mosavat. The use of Chinese herbal drugs in Islamic medicine. Journal of Integrative Medicine, 2015, 13(6): 363-367.
[15] Wei Chiang Chan Eric, Kuin Wong Siu. Phytochemistry and pharmacology of ornamental gingers, Hedychium coronarium and Alpinia purpurata: A review. Journal of Integrative Medicine, 2015, 13(6): 368-379.
Full text



[1] Jin-zhou Tian, Jing Shi, Xin-qing Zhang, Qi Bi, Xin Ma, Zhi-liang Wang, Xiao-bin Li, Shu-li Shen, Lin Li, Zhen-yun Wu, Li-yan Fang, Xiao-dong Zhao, Ying-chun Miao, Peng-wen Wang, Ying Ren, Jun-xiang Yin, Yong-yan Wang, Beijing United Study Group on MCI of the Capital Foundation of Medical Developments. An explanation on "guiding principles of clinical research on mild cognitive impairment (protocol)". Journal of Chinese Integrative Medicine, 2008, 6(1): 15-21
[2] Yi-ting He, Qing-lin Zha, Jian-ping Yu, Yong Tan, Cheng Lu, Ai-ping Lv. Principal factor analysis of symptoms of rheumatoid arthritis and their correlations with efficacy of traditional Chinese medicine and Western medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 32-36
[3] Jun Cai, Hua Wang, Sheng Zhou, Bin Wu, Hua-rong Song, Zheng-rong Xuan. Effect of Sijunzi Decoction and enteral nutrition on T-cell subsets and nutritional status in patients with gastric cancer after operation: A randomized controlled trial. Journal of Chinese Integrative Medicine, 2008, 6(1): 37-40
[4] Wei Zhang, Xiang-feng Lu, Xiao-mei Zhang, Jian-jun Wu, Liang-duo Jiang. A rat model of pulmonary fibrosis induced by infusing bleomycin quickly through tracheal intubation. Journal of Chinese Integrative Medicine, 2008, 6(1): 60-67
[5] A-gao Zhou, Yong Zhang, Gang Kui, De-Yun Kong, Hai-liang Ge, Qiu-hua Ren, Jia-rong Dong, Sheng Hong, Xu-ming Mao, Yin Wang, Hui-zheng Zhang, Shu-jun Wang. Influence of traditional Chinese compound recipes with different efficacy on body weight, tumor weight and immune function in H22 cancer-bearing mice. Journal of Chinese Integrative Medicine, 2008, 6(1): 77-82
[6] Guo-hong Yuan, Xiao-jing Pang, He-chao Ma. Synergic effects of Danggui Buxue Decoction in reducing toxicity of cytoxan in tumor-bearing mice. Journal of Chinese Integrative Medicine, 2008, 6(1): 83-88
[7] Li Zhou, Hong-xing Zhang, Ling-guang Liu, Wen-jun Wan. Effect of electro-acupuncture at Fenglong (GV 16) on nitric oxide and endothelin in rats with hyperlipidemia. Journal of Chinese Integrative Medicine, 2008, 6(1): 89-92
[8] Jin-zhou Tian, Jing Shi, Xin-qing Zhang, Qi Bi, Xin Ma, Zhi-liang Wang, Xiao-bin Li, Shu-li Shen, Lin Li, Zhen-yun Wu, Li-yan Fang, Xiao-dong Zhao, Ying-chun Miao, Peng-wen Wang, Ying Ren, Jun-xiang Yin, Yong-yan Wang, Beijing United Study Group on MCI of the Capital Foundation of Medical Developments. Guiding principles of clinical research on mild cognitive impairment (protocol). Journal of Chinese Integrative Medicine, 2008, 6(1): 9-14
[9] Xin-jun Wang, Ling-ling Wang . A mechanism of endogenous opioid peptides for rapid onset of acupuncture effect in treatment of depression. Journal of Chinese Integrative Medicine, 2010, 8(11): 1014-1017
[10] Bo Wang , Wei Yan , Li-hui Hou, Xiao-ke Wu. Disorder of Tiangui (kidney essence) and reproductive dysfunction in patients with polycystic ovary syndrome. Journal of Chinese Integrative Medicine, 2010, 8(11): 1018-1022