Advertisement

Treatment of atherosclerosis by traditional Chinese medicine: Questions and quandaries

      Highlights

      • The first review article to address whether Chinese herb medicines can treat atherosclerosis.
      • What is known and unknown about Chinese herb medicine for the treatment of atherosclerosis
      • Con and pro of Chinese herb medicine for atherosclerosis compared with Western medicine.

      Abstract

      Atherosclerosis and its complications, such as myocardial infarction and stroke, are the major causes of morbidity and mortality, and development of effective therapies for both prevention and treatment of this disease is critically important. Currently, there are many drugs available for atherosclerotic disease, but the lipid-lowering drugs statins are still the first-choice for treatment of hypercholesterolemia, a major risk factor for atherosclerosis. On the other hand, traditional Chinese medicines, mainly Chinese herbal medicines (CHM), have been widely used in China and in other Asian countries for the treatment of atherosclerotic diseases. Although many CHMs have been reported to be effective for treating atherosclerotic diseases for more than two thousand years, there are still many difficulties for their use, such as lack of scientific evidence assessed by rigorous clinical trials, complicated components and unclear pharmacological mechanisms, which often hamper the widespread use of CHMs in Western countries. Due to these concerns, CHMs are usually considered as complimentary or alternative treatment for atherosclerotic diseases. In this review, we provide an overview of the pathophysiology of atherosclerosis viewed by Western and traditional Chinese medicine, summarize pros and cons on the efficacy of CHMs for atherosclerosis and discuss what is necessary for CHM use to spread to Western societies.

      Keywords

      Abbreviations

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

      1. WHO Tradtional Medicine Stratery 2014-2023. 2013
        • Wu C.H.
        • Wang C.C.
        • Tsai M.T.
        • et al.
        Trend and Pattern of Herb and Supplement Use in the United States: Results from the 2002, 2007, and 2012 National Health Interview Surveys.
        Evid-Based Compl Alt, 2014
        • Tachjian A.
        • Maria V.
        • Jahangir A.
        Use of herbal products and potential interactions in patients with cardiovascular diseases.
        J. Am. Coll. Cardiol. 2010; 55: 515-525
        • Thompson R.C.
        • Allam A.H.
        • Lombardi G.P.
        • et al.
        Atherosclerosis across 4000 years of human history: the Horus study of four ancient populations.
        Lancet. 2013; 381: 1211-1222
        • Allam A.H.
        • Thompson R.C.
        • Wann L.S.
        • et al.
        Atherosclerosis in ancient Egyptian mummies: the Horus study.
        JACC. Cardiovascular imaging. 2011; 4: 315-327
        • Cheng T.O.
        Coronary arteriosclerotic disease existed in China over 2,200 years ago.
        Methodist DeBakey cardiovascular journal. 2012; 8: 47-48
        • Hanke H.
        • Lenz C.
        • Finking G.
        The discovery of the pathophysiological aspects of atherosclerosis--a review.
        Acta Chirurgica Belgica. 2001; 101: 162-169
        • Konstantinov I.E.
        • Mejevoi N.
        • Anichkov N.M.
        • Nikolai N.
        Anichkov and his theory of atherosclerosis.
        Tex. Heart Inst. J. 2006; 33: 417-423
        • Steinberg D.
        Thematic review series: the pathogenesis of atherosclerosis. An interpretive history of the cholesterol controversy: part I.
        J. Lipid Res. 2004; 45: 1583-1593
        • Castelli W.P.
        Cholesterol and lipids in the risk of coronary artery disease--the Framingham Heart Study.
        Can. J. Cardiol. 1988; 4: 5A-10A
        • Cannon C.P.
        • Steinberg B.A.
        • Murphy S.A.
        • et al.
        Meta-analysis of cardiovascular outcomes trials comparing intensive versus moderate statin therapy.
        J. Am. Coll. Cardiol. 2006; 48: 438-445
        • Raal F.
        • Scott R.
        • Somaratne R.
        • et al.
        Low-density lipoprotein cholesterol-lowering effects of AMG 145, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease in patients with heterozygous familial hypercholesterolemia: the Reduction of LDL-C with PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD) randomized trial.
        Circulation. 2012; 126: 2408-2417
        • Reiner Z.
        Resistance and intolerance to statins, Nutrition, metabolism, and cardiovascular diseases.
        Nutr. Metabol. Cardiovasc. Dis. 2014; 24: 1057-1066
        • Baigent C.
        • Keech A.
        • Kearney P.M.
        • et al.
        Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins.
        Lancet. 2005; 366: 1267-1278
        • Baigent C.
        • Blackwell L.
        • Emberson J.
        • et al.
        Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials.
        Lancet. 2010; 376: 1670-1681
        • Brautbar A.
        • Ballantyne C.M.
        Pharmacological strategies for lowering LDL cholesterol: statins and beyond.
        Nat. Rev. Cardiol. 2011; 8: 253-265
        • Bartecchi C.E.
        Complementary medicine has No place in cardiovascular medicine.
        J. Am. Coll. Cardiol. 2006; 47: 1498-1499
        • Ross R.
        Atherosclerosis--an inflammatory disease.
        N. Engl. J. Med. 1999; 340: 115-126
        • Fan J.
        • Watanabe T.
        Inflammatory reactions in the pathogenesis of atherosclerosis.
        J. Atherosclerosis Thromb. 2003; 10: 63-71
      2. Japan Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardivascular Diseases 2017. Nanao Publishing Com., Tokyo2017
        • Yang Y.Z.
        • Liu L.S.
        The history of Chinese atherosclerosis research.
        J Chin Arterioscler. 2014; 22: 95-104
        • Oppenheim F.
        Review of one hundred autopsies of Shanghai Chinese.
        Chin. Med. J. 1925; 39: 1011-1076
        • Z L.
        Coronary atherosclerosis and syphilis pathology.
        Chin Med J (in Chinese). 1934; 20: 488-498
        • Xing Y.
        • Hu D.
        • Zhang T.
        • et al.
        Traditional Chinese medicine and vascular disease, evidence-based complementary and alternative medicine.
        eCAM. 2015; : 430818
        • Liu Q.
        • Li J.
        • Hartstone-Rose A.
        • et al.
        Chinese herbal compounds for the prevention and treatment of atherosclerosis: experimental evidence and mechanisms, evidence-based complementary and alternative medicine.
        eCAM. 2015; : 752610
        • Hao P.
        • Jiang F.
        • Cheng J.
        • et al.
        Traditional Chinese medicine for cardiovascular disease: evidence and potential mechanisms.
        J. Am. Coll. Cardiol. 2017; 69: 2952-2966
        • Wang J.
        • Lin F.
        • Guo L.L.
        • et al.
        Cardiovascular disease, mitochondria, and traditional Chinese medicine, evidence-based complementary and alternative medicine.
        eCAM, 2015: 143145
        • Chen K.B.
        • Chen H.Y.
        • Chen K.C.
        • et al.
        Treatment of cardiovascular disease by traditional Chinese medicine against pregnane X receptor.
        BioMed Res. Int. 2014; 2014: 950191
        • Xu Z.
        • Zhang N.L.
        • Wang Y.
        • et al.
        Statistical validation of Traditional Chinese Medicine syndrome postulates in the context of patients with cardiovascular disease.
        J. Alternative Compl. Med. 2013; 19: 799-804
        • Li X.
        • Xu X.
        • Wang J.
        • et al.
        A system-level investigation into the mechanisms of Chinese Traditional Medicine: compound Danshen Formula for cardiovascular disease treatment.
        PLoS One. 2012; 7e43918
        • Khor G.L.
        Cardiovascular epidemiology in the Asia-Pacific region.
        Asia Pac. J. Clin. Nutr. 2001; 10: 76-80
        • Chen W.
        • Gao R.
        • Liu L.
        • et al.
        China cardiovascular disease report 2016.
        Chin Circulation J. 2017; 32: 521-531
        • Shi D.
        • Chen K.
        Recent development of traditional Chinese medicine in prevention and treatment of atherosclerosis.
        J. Tradit. Chin. Med. 1996; 16: 293-298
        • Hunter P.M.
        • Hegele R.A.
        Functional foods and dietary supplements for the management of dyslipidaemia.
        Nat. Rev. Endocrinol. 2017; 13: 278-288
        • Cicero A.F.G.
        • Colletti A.
        • Bajraktari G.
        • et al.
        Lipid-lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel.
        Nutr. Rev. 2017; 75: 731-767
        • Aggarwal M.
        • Aggarwal B.
        • Rao J.
        Integrative medicine for cardiovascular disease and prevention.
        Med. Clin. 2017; 101: 895-923
        • Hasani-Ranjbar S.
        • Nayebi N.
        • Moradi L.
        • et al.
        The efficacy and safety of herbal medicines used in the treatment of hyperlipidemia; a systematic review.
        Curr. Pharmaceut. Des. 2010; 16: 2935-2947
        • Zou P.
        Traditional Chinese medicine, food therapy, and hypertension control: a narrative review of Chinese literature.
        Am. J. Chin. Med. 2016; 44: 1579-1594
        • Chan Q.
        • Stamler J.
        • Brown I.J.
        • et al.
        Relation of raw and cooked vegetable consumption to blood pressure: the INTERMAP Study.
        J. Hum. Hypertens. 2014; 28: 353-359
        • Ried K.
        • Toben C.
        • Fakler P.
        Effect of garlic on serum lipids: an updated meta-analysis.
        Nutr. Rev. 2013; 71: 282-299
        • Qidwai W.
        • Ashfaq T.
        Role of garlic usage in cardiovascular disease prevention: an evidence-based approach, Evidence-based complementary and alternative medicine.
        eCAM. 2013; : 125649
        • Guo M.
        • Liu Y.
        • Gao Z.Y.
        • et al.
        Chinese herbal medicine on dyslipidemia: progress and perspective, Evidence-based complementary and alternative medicine.
        eCAM. 2014; : 163036
        • Xiong X.
        • Yang X.
        • Liu Y.
        • et al.
        Chinese herbal formulas for treating hypertension in traditional Chinese medicine: perspective of modern science.
        Hypertens. Res. 2013; 36: 570-579
        • Zhang J.
        • Meng H.
        • Zhang Y.
        • et al.
        The therapeutical effect of Chinese medicine for the treatment of atherosclerotic coronary heart disease.
        Curr. Pharmaceut. Des. 2017; 23: 5086-5096
        • Lu Z.
        • Kou W.
        • Du B.
        • et al.
        Effect of Xuezhikang, an extract from red yeast Chinese rice, on coronary events in a Chinese population with previous myocardial infarction.
        Am. J. Cardiol. 2008; 101: 1689-1693
        • Liu J.
        • Henkel T.
        Traditional Chinese medicine (TCM): are polyphenols and saponins the key ingredients triggering biological activities?.
        Curr. Med. Chem. 2002; 9: 1483-1485
        • Li L.
        • Zhou X.
        • Li N.
        • et al.
        Herbal drugs against cardiovascular disease: traditional medicine and modern development.
        Drug Discovery Today. 2015; 20: 1074-1086
        • Liu C.
        • Huang Y.
        Chinese herbal medicine on cardiovascular diseases and the mechanisms of action.
        Front. Pharmacol. 2016; 7: 469
        • Liperoti R.
        • Vetrano D.L.
        • Bernabei R.
        • et al.
        Herbal medications in cardiovascular medicine.
        J. Am. Coll. Cardiol. 2017; 69: 1188-1199
        • Peng Y.
        • Ye H.
        • Zhao N.
        Clinical analysis on Kaiyu Qingre treatment for type 2 diabetes mellitus with hyperuricemia.
        Clin J Chinese Med (in Chinese). 2014; 6: 53-55
        • Chen L.
        • Liu M.
        Clinical research on treating 58 patients with type 2 diabetes mellitus complicated with hyperlipidemia by Dachaihu decoction.
        New J Tradit Chinese Med (in Chinese). 2015; 37: 36-37
        • Lin B.
        Treatment of 82 cases of hyperlipidemia with Jiawei Erchen decoction.
        J Sichuan Tradit Chinese Med (in Chinese). 2012; 20: 36-37
        • Ding Q.
        Clinical observation on the treatment of mixed hyperlipidemia with Shanzha Erchen Decoction.
        Clin J Tradit Chinese Med (in Chinese). 2013; 25: 319-320
        • Zhao L.
        • Huang W.
        • Yan X.
        Effect of Liuwei Dihuang pill on hyperlipidemia and obesity in 30 Patients with senile nephrotic syndrome during hormone therapy.
        Chinese J Gerontol (in Chinese). 2010; 30: 981-982
        • Liu T.
        Clinical study of Liuwei Dihuang pill on type 2 diabetes mellitus with hyperlipidemia.
        Asia-Pacific Tradit Med. 2015; 11: 134-135
        • Moriarty P.M.
        • Roth E.M.
        • Karns A.
        • et al.
        Effects of Xuezhikang in patients with dyslipidemia: a multicenter, randomized, placebo-controlled study.
        J Clin Lipidol. 2014; 8: 568-575
        • Lu Z.
        • Qiu Y.
        • Liu S.
        • et al.
        Clinical evaluation of Xuezhikang treatment of hyperlipidemia.
        Chinese Circulation J (in Chinese). 1997; 12: 14-17
        • Jing A.
        • Li-Mei Z.
        • Yan-Jie L.
        • et al.
        A randomized, multicentre, open-label, parallel-group trial to compare the efficacy and safety profile of daming capsule in patients with hypercholesterolemia.
        Phytother Res.: PTR. 2009; 23: 1039-1042
        • Dalli E.
        • Colomer E.
        • Tormos M.C.
        • et al.
        Crataegus laevigata decreases neutrophil elastase and has hypolipidemic effect: a randomized, double-blind, placebo-controlled trial.
        Phytomedicine. 2011; 18: 769-775
        • Huo S.
        Clinical study on lipid lowering effect of Shanzhajing Jiangzhi tablets and simvastatin tablets.
        Inner Mongolia J Tradit Chinese Med (in Chinese). 2009; 28: 66-76
        • Bhaskar S.
        • Kumar K.S.
        • Krishnan K.
        • et al.
        Quercetin alleviates hypercholesterolemic diet induced inflammation during progression and regression of atherosclerosis in rabbits.
        Nutrition. 2013; 29: 219-229
        • Basu A.
        • Das A.S.
        • Majumder M.
        • et al.
        Antiatherogenic roles of dietary flavonoids Chrysin, Quercetin, and Luteolin.
        J. Cardiovasc. Pharmacol. 2016; 68: 89-96
        • Mulvihill E.E.
        • Assini J.M.
        • Sutherland B.G.
        • et al.
        Naringenin decreases progression of atherosclerosis by improving dyslipidemia in high-fat-fed low-density lipoprotein receptor-null mice.
        Arterioscler. Thromb. Vasc. Biol. 2010; 30: 742-748
        • Burke A.C.
        • Sutherland B.G.
        • Telford D.E.
        • et al.
        Intervention with citrus flavonoids reverses obesity, and improves metabolic syndrome and atherosclerosis in obese Ldlr-/- mice.
        J. Lipid Res. 2018 Jul 15; (pii: jlr.M087387. [Epub ahead of print])
        • Mulvihill E.E.
        • Burke A.C.
        • Huff M.W.
        Citrus flavonoids as regulators of lipoprotein metabolism and atherosclerosis.
        Annu. Rev. Nutr. 2016; 36: 275-299
        • Liu L.
        • Nagai I.
        • Gao Y.
        • et al.
        Effects of catechins and caffeine on the development of atherosclerosis in mice.
        Biosci. Biotechnol. Biochem. 2017; 81: 1948-1955
        • Mangels D.R.
        • Mohler 3rd, E.R.
        Catechins as potential mediators of cardiovascular health.
        Arterioscler. Thromb. Vasc. Biol. 2017; 37: 757-763
        • Chang C.J.
        • Tzeng T.F.
        • Liou S.S.
        • et al.
        Myricetin increases hepatic peroxisome proliferator-activated receptor alpha protein expression and decreases plasma lipids and adiposity in rats.
        Evid Based Complement Alternat Med. 2012; : 787152
        • Lian T.W.
        • Wang L.
        • Lo Y.H.
        • et al.
        Fisetin, morin and myricetin attenuate CD36 expression and oxLDL uptake in U937-derived macrophages.
        Biochim. Biophys. Acta. 2008; 1781: 601-609
        • Goh F.Y.
        • Upton N.
        • Guan S.
        • et al.
        Fisetin, a bioactive flavonol, attenuates allergic airway inflammation through negative regulation of NF-kappaB.
        Eur. J. Pharmacol. 2012; 679: 109-116
        • Salvamani S.
        • Gunasekaran B.
        • Shaharuddin N.A.
        • et al.
        Antiartherosclerotic effects of plant flavonoids.
        BioMed Res. Int. 2014; : 480258
        • Chen J.H.
        • Tsai C.W.
        • Wang C.P.
        • et al.
        Anti-atherosclerotic potential of gossypetin via inhibiting LDL oxidation and foam cell formation.
        Toxicol. Appl. Pharmacol. 2013; 272: 313-324
        • Li Y.
        • Qin R.
        • Yan H.
        • et al.
        Inhibition of vascular smooth muscle cells premature senescence with rutin attenuates and stabilizes diabetic atherosclerosis.
        J. Nutr. Biochem. 2018; 51: 91-98
        • Kanashiro A.
        • Andrade D.C.
        • Kabeya L.M.
        • et al.
        Modulatory effects of rutin on biochemical and hematological parameters in hypercholesterolemic Golden Syrian hamsters.
        An. Acad. Bras. Cienc. 2009; 81: 67-72
        • Kong L.
        • Luo C.
        • Li X.
        • et al.
        The anti-inflammatory effect of kaempferol on early atherosclerosis in high cholesterol fed rabbits.
        Lipids Health Dis. 2013; 12: 115
        • Xiao H.B.
        • Lu X.Y.
        • Sun Z.L.
        • et al.
        Kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of apolipoprotein E deficient mice.
        Toxicol. Appl. Pharmacol. 2011; 257: 405-411
        • Qin H.
        • Liu P.
        • Lin S.
        Effects of astragaloside IV on the SDF-1/CXCR4 expression in atherosclerosis of apoE(-/-) mice induced by hyperlipaemia.
        Evid Based Complement Alternat Med. 2015; : 385154
        • Wang C.
        • Li Y.
        • Hao M.
        • et al.
        Astragaloside IV inhibits triglyceride accumulation in insulin-resistant HepG2 cells via AMPK-induced SREBP-1c phosphorylation.
        Front. Pharmacol. 2018; 9: 345
        • Koo H.J.
        • Park H.J.
        • Byeon H.E.
        • et al.
        Chinese yam extracts containing beta-sitosterol and ethyl linoleate protect against atherosclerosis in apolipoprotein E-deficient mice and inhibit muscular expression of VCAM-1 in vitro.
        J. Food Sci. 2014; 79: H719-H729
        • Cicero A.F.
        • Minardi M.
        • Mirembe S.
        • et al.
        Effects of a new low dose soy protein/beta-sitosterol association on plasma lipid levels and oxidation.
        Eur. J. Nutr. 2004; 43: 319-322
        • Wu P.
        • Gao H.
        • Liu J.X.
        • et al.
        Triterpenoid saponins with anti-inflammatory activities from Ilex pubescens roots.
        Phytochemistry. 2017; 134: 122-132
        • Huang X.J.
        • Tang J.Q.
        • Li M.M.
        • et al.
        Triterpenoid saponins from the rhizomes of Anemone flaccida and their inhibitory activities on LPS-induced NO production in macrophage RAW264.7 cells.
        J. Asian Nat. Prod. Res. 2014; 16: 910-921
        • Yang K.
        • Luo Y.
        • Lu S.
        • et al.
        Salvianolic acid B and ginsenoside Re synergistically protect against Ox-LDL-induced endothelial apoptosis through the antioxidative and antiinflammatory mechanisms.
        Front. Pharmacol. 2018; 9: 662
        • Quan H.Y.
        • Yuan H.D.
        • Jung M.S.
        • et al.
        Ginsenoside Re lowers blood glucose and lipid levels via activation of AMP-activated protein kinase in HepG2 cells and high-fat diet fed mice.
        Int. J. Mol. Med. 2012; 29: 73-80
        • Guo M.
        • Xiao J.
        • Sheng X.
        • et al.
        Ginsenoside Rg3 mitigates atherosclerosis progression in diabetic apoE-/- mice by skewing macrophages to the M2 phenotype.
        Front. Pharmacol. 2018; 9: 464
        • Saba E.
        • Kim S.H.
        • Kim S.D.
        • et al.
        Alleviation of diabetic complications by ginsenoside Rg3-enriched red ginseng extract in western diet-fed LDL(-/-) mice.
        J Ginseng Res. 2018; 42: 352-355
        • Yang K.
        • Zhang H.
        • Luo Y.
        • et al.
        Gypenoside XVII prevents atherosclerosis by attenuating endothelial apoptosis and oxidative stress: insight into the ERalpha-mediated PI3K/akt pathway.
        Int. J. Mol. Sci. 2017; 18
        • Yang Y.H.
        • Yang J.
        • Jiang Q.H.
        Hypolipidemic effect of gypenosides in experimentally induced hypercholesterolemic rats.
        Lipids Health Dis. 2013; 12: 154
        • Binesh A.
        • Devaraj S.N.
        • Halagowder D.
        Atherogenic diet induced lipid accumulation induced NFkappaB level in heart, liver and brain of Wistar rat and diosgenin as an anti-inflammatory agent.
        Life Sci. 2018; 196: 28-37
        • Wang P.
        • He L.Y.
        • Shen G.D.
        • et al.
        Inhibitory effects of Dioscin on atherosclerosis and foam cell formation in hyperlipidemia rats.
        Inflammopharmacology. 2017; 25: 633-642