Herbal Remedies Supply a Novel Prospect for the Treatment of Atherosclerosis: A Review of Current Mechanism Studies
Yu Zeng
Department of Pharmacology, Guiyang Medical University, Guiyang, China
Search for more papers by this authorJu-Xian Song
School of Chinese Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
Search for more papers by this authorCorresponding Author
Xiang-Chun Shen
Department of Pharmacology, Guiyang Medical University, Guiyang, China
X.-C. Shen, Department of Pharmacology, Guiyang Medical University, Guiyang 550004, China.
E-mail: [email protected]
Search for more papers by this authorYu Zeng
Department of Pharmacology, Guiyang Medical University, Guiyang, China
Search for more papers by this authorJu-Xian Song
School of Chinese Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
Search for more papers by this authorCorresponding Author
Xiang-Chun Shen
Department of Pharmacology, Guiyang Medical University, Guiyang, China
X.-C. Shen, Department of Pharmacology, Guiyang Medical University, Guiyang 550004, China.
E-mail: [email protected]
Search for more papers by this authorAbstract
Atherosclerosis (AS) is a systemic cardiovascular disease with complicated pathogenesis involving oxidative stress, endothelial dysfunction and chronic inflammation. Increasing lines of evidence have questioned the statins-dominated treatment for AS, including their dangerous side-effects such as the breakdown of muscle when taken in larger doses. A multifaceted approach that addresses all major risk factors or pathological targets may provide an ideal treatment for AS. Studies of the herbal remedies on the prevention and treatment of AS have received much attention in recent years. This review summarizes some important experimental findings regarding their mechanisms of action on AS. Using the pre-set PUBMED searching syntax and inclusion criteria, representative citations published in English concerning the experimental studies of 14 herbal materials were included. We found that many extracts and (or) single compounds from these herbal materials, such as Salvia miltiorrhiza, Curcuma longa, Rheum undulatum and Panax notoginseng, could regulate multiple key targets involved in the initiation and propagation of AS. Some important findings about the effects of herbal formulations on AS were also reviewed. Given the complicated nature of AS and the holistic, combinational approach of herbal remedies, we propose that mixed herbal preparations with multiple active ingredients may be preferable for the prevention and treatment of AS. Further rigorously designed pharmacological evaluation and multi-centred clinical trials are warranted. Copyright © 2011 John Wiley & Sons, Ltd.
REFERENCES
- Antons KA, Williams CD, Baker SK, et al. 2006. Clinical perspectives of statin-induced rhabdomyolysis. Am J Med 119: 400–409.
- Belinky PA, Aviram M, Fuhrman B, et al. 1998. The antioxidative effects of the isoflavan glabridin on endogenous constituents of LDL during its oxidation. Atherosclerosis 137: 49–61.
- Call JT, Deliargyris EN, Newby LK. 2004. Focusing on inflammation in the treatment of atherosclerosis. Cardiol Rev 12: 194–200.
- Chan KC, Ho HH, Huang CN, et al. 2009. Mulberry leaf extract inhibits vascular smooth muscle cell migration involving a block of small GTPase and Akt/NF-kappaB signals. J Agric Food Chem 57: 9147–9153.
- Chan MM. 1995. Inhibition of tumor necrosis factor by curcumin, a phytochemical. Biochem Pharmacol 49: 1551–1556.
- Chang YL, Chen CL, Kuo CL, et al. 2010. Glycyrrhetinic acid inhibits ICAM-1 expression via blocking JNK and NF-kappaB pathways in TNF-alpha-activated endothelial cells. Acta Pharmacol Sin 31: 546–553.
- Chen CC, Hsu JD, Wang SF, et al. 2003. Hibiscus sabdariffa extract inhibits the development of atherosclerosis in cholesterol-fed rabbits. J Agric Food Chem 51: 5472–5477.
- Chen FL, Yang ZH, Liu Y, et al. 2008. Berberine inhibits the expression of TNFalpha, MCP-1, and IL-6 in AcLDL-stimulated macrophages through PPARgamma pathway. Endocrine 33: 331–337.
- Chen L, Wang WY, Wang YP. 2009a. Inhibitory effects of lithospermic acid on proliferation and migration of rat vascular smooth muscle cells. Acta Pharmacol Sin 30: 1245–1252.
- Chen WQ, Zhong L, Zhang L, et al. 2009b. Chinese medicine tongxinluo significantly lowers serum lipid levels and stabilizes vulnerable plaques in a rabbit model. J Ethnopharmacol 124: 103–110.
- Chen YH, Lin SJ, Ku HH, et al. 2001. Salvianolic acid B attenuates VCAM-1 and ICAM-1 expression in TNF-alpha-treated human aortic endothelial cells. J Cell Biochem 82: 512–521.
- Cho BJ, Im EK, Kwon JH, et al. 2005. Berberine inhibits the production of lysophosphatidylcholine-induced reactive oxygen species and the ERK1/2 pathway in vascular smooth muscle cells. Mol Cells 20: 429–434.
- Choi JH, Rho MC, Lee SW, et al. 2007. Glabrol, an acyl-coenzyme A: cholesterol acyltransferase inhibitor from licorice roots. J Ethnopharmacol 110: 563–566.
- Chung HJ, Maruyama I, Tani T. 2003. Saiko-ka-Ryukotsu-Borei-To inhibits intimal thickening in carotid artery after balloon endothelial denudation in cholesterol-fed rats. Biol Pharm Bull 26: 56–60.
- Cicero AF, Rovati LC, Setnikar I. 2007. Eulipidemic effects of berberine administered alone or in combination with other natural cholesterol-lowering agents. A single-blind clinical investigation. Arzneimittelforschung 57: 26–30.
- Demeule M, Michaud-Levesque J, Annabi B, et al. 2002. Green tea catechins as novel antitumor and antiangiogenic compounds. Curr Med Chem Anticancer Agents 2: 441–463.
- Ding M, Ye TX, Zhao GR, et al. 2005a. Aqueous extract of Salvia miltiorrhiza attenuates increased endothelial permeability induced by tumor necrosis factor-alpha. Int Immunopharmacol 5: 1641–1651.
- Ding M, Zhao GR, Yuan YJ, et al. 2005b. Aqueous extract of Salvia miltiorrhoza regulates adhesion molecule expression of tumor necrosis factor alpha-induced endothelial cells by blocking activation of nuclear factor kappaB. J Cardiovasc Pharmacol 45: 516–524.
- El-Beshbishy HA, Singab AN, Sinkkonen J, et al. 2006. Hypolipidemic and antioxidant effects of Morus alba L. (Egyptian mulberry) root bark fractions supplementation in cholesterol-fed rats. Life Sci 78: 2724–2733.
- Fadini GP, Manzato E, Crepaldi C, et al. 2010. Two cases of statin-induced rhabdomyolysis associated with mononeuropathy. Clin Drug Investig 30: 347–350.
- Fan E, Zhang L, Jiang S, et al. 2008. Beneficial effects of resveratrol on atherosclerosis. J Med Food 11: 610–614.
- Fang ZY, Lin R, Yuan BX, et al. 2008. Tanshinone IIA downregulates the CD40 expression and decreases MMP-2 activity on atherosclerosis induced by high fatty diet in rabbit. J Ethnopharmacol 115: 217–222.
- Glass CK, Witztum JL. 2001. Atherosclerosis. the road ahead. Cell 104: 503–516.
- Gorinstein S, Jastrzebski Z, Namiesnik J, et al. 2007. The atherosclerotic heart disease and protecting properties of garlic: contemporary data. Mol Nutr Food Res 51: 1365–1381.
- Grundy SM. 2002. Alternative approaches to cholesterol-lowering therapy. Am J Cardiol 90: 1135–1138.
- Guan S, Wang B, Li W, et al. 2010. Effects of berberine on expression of LOX-1 and SR-BI in human macrophage-derived foam cells induced by ox-LDL. Am J Chin Med 38: 1161–1169.
- Han JM, Kim MJ, Baek SH, et al. 2009. Antiatherosclerotic effects of Artemisia princeps Pampanini cv. Sajabal in LDL receptor deficient mice. J Agric Food Chem 57: 1267–1274.
- Harauma A, Murayama T, Ikeyama K, et al. 2007. Mulberry leaf powder prevents atherosclerosis in apolipoprotein E-deficient mice. Biochem Biophys Res Commun 358: 751–756.
- Hei ZQ, Huang HQ, Tan HM, et al. 2006. Emodin inhibits dietary induced atherosclerosis by antioxidation and regulation of the sphingomyelin pathway in rabbits. Chin Med J (Engl) 119: 868–870.
- Ho HH, Hsu LS, Chan KC, et al. 2010. Extract from the leaf of nucifera reduced the development of atherosclerosis via inhibition of vascular smooth muscle cell proliferation and migration. Food Chem Toxicol 48: 159–168.
- Hsieh YS, Kuo WH, Lin TW, et al. 2007. Protective effects of berberine against low-density lipoprotein (LDL) oxidation and oxidized LDL-induced cytotoxicity on endothelial cells. J Agric Food Chem 55: 10437–10445.
- Huang Z, Wang L, Meng S, et al. 2011. Berberine reduces both MMP-9 and EMMPRIN expression through prevention of p38 pathway activation in PMA-induced macrophages. Int J Cardiol 146: 153–158.
- Ji W, Gong BQ. 2007. Hypolipidemic effects and mechanisms of Panax notoginseng on lipid profile in hyperlipidemic rats. J Ethnopharmacol 113: 318–324.
- Jia X, Chen Y, Zidichouski J, et al. 2008. Co-administration of berberine and plant stanols synergistically reduces plasma cholesterol in rats. Atherosclerosis 201: 101–107.
- Jin UH, Kang SK, Suh SJ, et al. 2006. Inhibitory effect of Salvia miltiorrhia BGE on matrix metalloproteinase-9 activity and migration of TNF-alpha-induced human aortic smooth muscle cells. Vascul Pharmacol 44: 345–353.
- Kao ES, Tseng TH, Lee HJ, et al. 2009. Anthocyanin extracted from Hibiscus attenuate oxidized LDL-mediated foam cell formation involving regulation of CD36 gene. Chem Biol Interact 179: 212–218.
- Katsuda S, Suzuki K, Koyama N, et al. 2009. Safflower seed polyphenols (N-(p-coumaroyl)serotonin and N-feruloylserotonin) ameliorate atherosclerosis and distensibility of the aortic wall in Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits. Hypertens Res 32: 944–949.
- Kawashima S, Yokoyama M. 2004. Dysfunction of endothelial nitric oxide synthase and atherosclerosis. Arterioscler Thromb Vasc Biol 24: 998–1005.
- Kim BJ, Kim YK, Park WH, et al. 2003. A water-extract of the Korean traditional formulation Geiji-Bokryung-Hwan reduces atherosclerosis and hypercholesteremia in cholesterol-fed rabbits. Int Immunopharmacol 3: 723–734.
- Kim DW, Chung HJ, Nose K, et al. 2002. Preventive effects of a traditional Chinese formulation, Chaihu-jia-Longgu-Muli-tang, on intimal thickening of carotid artery injured by balloon endothelial denudation in rats. J Pharm Pharmacol 54: 571–575.
- Kim MJ, Han JM, Jin YY, et al. 2008. In vitro antioxidant and anti-inflammatory activities of Jaceosidin from Artemisia princeps Pampanini cv. Sajabal. Arch Pharm Res 31: 429–437.
- Koyama N, Kuribayashi K, Seki T, et al. 2006. Serotonin derivatives, major safflower (Carthamus tinctorius L.) seed antioxidants, inhibit low-density lipoprotein (LDL) oxidation and atherosclerosis in apolipoprotein E-deficient mice. J Agric Food Chem 54: 4970–4976.
- Lee H-J, Chen C-C, Chou F-P, et al. 2010a. Water extracts from Nelumbo nucifera leaf reduced plasma lipids and atherosclerosis in cholesterol fed rabbits. J Food Biochem 34: 779–795.
- Lee S, Lim HJ, Park HY, et al. 2006. 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 186: 29–37.
- Lee TS, Pan CC, Peng CC, et al. 2010b. Anti-atherogenic effect of berberine on LXRalpha-ABCA1-dependent cholesterol efflux in macrophages. J Cell Biochem 111: 104–110.
- Li H, Dai M, Jia W. 2009. Paeonol attenuates high-fat-diet-induced atherosclerosis in rabbits by anti-inflammatory activity. Planta Med 75: 7–11.
- Liang KW, Ting CT, Yin SC, et al. 2006. Berberine suppresses MEK/ERK-dependent Egr-1 signaling pathway and inhibits vascular smooth muscle cell regrowth after in vitro mechanical injury. Biochem Pharmacol 71: 806–817.
- Liu G, Wang B, Zhang J, et al. 2009. Total panax notoginsenosides prevent atherosclerosis in apolipoprotein E-knockout mice: Role of downregulation of CD40 and MMP-9 expression. J Ethnopharmacol 126: 350–354.
- Liu Y, Yan F, Zhang C, et al. 2008. Aqueous extract of rhubarb stabilizes vulnerable atherosclerotic plaques due to depression of inflammation and lipid accumulation. Phytother Res 22: 935–942.
- Liu Y, Zhang HG, Jia Y, et al. 2010. Panax notoginseng saponins attenuate atherogenesis accelerated by zymosan in rabbits. Biol Pharm Bull 33: 1324–1330.
- Meagher EA. 2003. Treatment of atherosclerosis in the new millennium: is there a role for vitamin E? Prev Cardiol 6: 85–90.
- Moon MK, Kang DG, Lee AS, et al. 2008. Anti-atherogenic effects of the aqueous extract of rhubarb in rats fed an atherogenic diet. Am J Chin Med 36: 555–568.
- Moon MK, Kang DG, Lee JK, et al. 2006. Vasodilatory and anti-inflammatory effects of the aqueous extract of rhubarb via a NO-cGMP pathway. Life Sci 78: 1550–1557.
- Nizamutdinova IT, Oh HM, Min YN, et al. 2007. Paeonol suppresses intercellular adhesion molecule-1 expression in tumor necrosis factor-alpha-stimulated human umbilical vein endothelial cells by blocking p38, ERK and nuclear factor-kappaB signaling pathways. Int Immunopharmacol 7: 343–350.
- Ochani PC, D'Mello P. 2009. Antioxidant and antihyperlipidemic activity of Hibiscus sabdariffa Linn. leaves and calyces extracts in rats. Indian J Exp Biol 47: 276–282.
- Olszanecki R, Jawien J, Gajda M, et al. 2005. Effect of curcumin on atherosclerosis in apoE/LDLR-double knockout mice. J Physiol Pharmacol 56: 627–635.
- Pan LL, Dai M. 2009. Paeonol from Paeonia suffruticosa prevents TNF-alpha-induced monocytic cell adhesion to rat aortic endothelial cells by suppression of VCAM-1 expression. Phytomedicine 16: 1027–1032.
- Piga R, Naito Y, Kokura S, et al. 2009. Inhibitory effect of serotonin derivatives on high glucose-induced adhesion and migration of monocytes on human aortic endothelial cells. Br J Nutr 102: 264–272.
- Qin L, Yang YB, Tuo QH, et al. 2009. Effects and underlying mechanisms of curcumin on the proliferation of vascular smooth muscle cells induced by Chol:MbetaCD. Biochem Biophys Res Commun 379: 277–282.
- Quiles JL, Mesa MD, Ramirez-Tortosa CL, et al. 2002. Curcuma longa extract supplementation reduces oxidative stress and attenuates aortic fatty streak development in rabbits. Arterioscler Thromb Vasc Biol 22: 1225–1231.
- Ramirez-Tortosa MC, Mesa MD, Aguilera MC, et al. 1999. Oral administration of a turmeric extract inhibits LDL oxidation and has hypocholesterolemic effects in rabbits with experimental atherosclerosis. Atherosclerosis 147: 371–378.
- Rosenblat M, Belinky P, Vaya J, et al. 1999. Macrophage enrichment with the isoflavan glabridin inhibits NADPH oxidase-induced cell-mediated oxidation of low density lipoprotein. A possible role for protein kinase C. J Biol Chem 274: 13790–13799.
- Sekiya N, Goto H, Tazawa K, et al. 2002. Keishi-bukuryo-gan preserves the endothelium dependent relaxation of thoracic aorta in cholesterol-fed rabbit by limiting superoxide generation. Phytother Res 16: 524–528.
- Sekiya N, Kainuma M, Hikiami H, et al. 2005. Oren-gedoku-to and Keishi-bukuryo-gan-ryo inhibit the progression of atherosclerosis in diet-induced hypercholesterolemic rabbits. Biol Pharm Bull 28: 294–298.
-
Sekiya N,
Tanaka N,
Itoh T, et al. 1999. Keishi-bukuryo-gan prevents the progression of atherosclerosis in cholesterol-fed rabbit. Phytother Res 13: 192–196.
10.1002/(SICI)1099-1573(199905)13:3<192::AID-PTR412>3.0.CO;2-2 CAS PubMed Web of Science® Google Scholar
- Shiao MS, Chiu JJ, Chang BW, et al. 2008. In search of antioxidants and anti-atherosclerotic agents from herbal medicines. Biofactors 34: 147–157.
- Shibata Y, Kume N, Arai H, et al. 2007. Mulberry leaf aqueous fractions inhibit TNF-alpha-induced nuclear factor kappaB (NF-kappaB) activation and lectin-like oxidized LDL receptor-1 (LOX-1) expression in vascular endothelial cells. Atherosclerosis 193: 20–27.
- Spinella M. 2002. The importance of pharmacological synergy in psychoactive herbal medicines. Altern Med Rev 7: 130–137.
- Steinberg D. 2005. Thematic review series: the pathogenesis of atherosclerosis. An interpretive history of the cholesterol controversy: part II: the early evidence linking hypercholesterolemia to coronary disease in humans. J Lipid Res 46: 179–190.
- Steinkamp-Fenske K, Bollinger L, Voller N, et al. 2007. Ursolic acid from the Chinese herb danshen (Salvia miltiorrhiza L.) upregulates eNOS and downregulates Nox4 expression in human endothelial cells. Atherosclerosis 195: e104–e111.
- Suh SJ, Jin UH, Choi HJ, et al. 2006. Cryptotanshinone from Salvia miltiorrhiza BUNGE has an inhibitory effect on TNF-alpha-induced matrix metalloproteinase-9 production and HASMC migration via down-regulated NF-kappaB and AP-1. Biochem Pharmacol 72: 1680–1689.
- Tam WY, Chook P, Qiao M, et al. 2009. The efficacy and tolerability of adjunctive alternative herbal medicine (Salvia miltiorrhiza and Pueraria lobata) on vascular function and structure in coronary patients. J Altern Complement Med 15: 415–421.
- Tripathi YB. 2009. BHUx: a patented polyherbal formulation to prevent hyperlipidemia and atherosclerosis. Recent Pat Inflamm Allergy Drug Discov 3: 49–57.
- Tripathi YB, Reddy MM, Pandey RS, et al. 2004. Anti-inflammatory properties of BHUx, a polyherbal formulation to prevent atherosclerosis. Inflammopharmacology 12: 131–152.
- Tripathi YB, Singh BK, Pandey RS, et al. 2005. BHUx: A patent polyherbal formulation to prevent atherosclerosis. Evid Based Complement Alternat Med 2: 217–221.
- Victor VM, Rocha M, Sola E, et al. 2009. Oxidative stress, endothelial dysfunction and atherosclerosis. Curr Pharm Des 15: 2988–3002.
- Wald NJ, Law MR. 2003. A strategy to reduce cardiovascular disease by more than 80%. BMJ 326: 1419.
- Wan JB, Lee SM, Wang JD, et al. 2009. Panax notoginseng reduces atherosclerotic lesions in ApoE-deficient mice and inhibits TNF-alpha-induced endothelial adhesion molecule expression and monocyte adhesion. J Agric Food Chem 57: 6692–6697.
- Wu YJ, Hong CY, Lin SJ, et al. 1998. Increase of vitamin E content in LDL and reduction of atherosclerosis in cholesterol-fed rabbits by a water-soluble antioxidant-rich fraction of Salvia miltiorrhiza. Arterioscler Thromb Vasc Biol 18: 481–486.
- Yan LP, Chan SW, Chan AS, et al. 2006. Puerarin decreases serum total cholesterol and enhances thoracic aorta endothelial nitric oxide synthase expression in diet-induced hypercholesterolemic rats. Life Sci 79: 324–330.
- Yang PY, Almofti MR, Lu L, et al. 2005. Reduction of atherosclerosis in cholesterol-fed rabbits and decrease of expressions of intracellular adhesion molecule-1 and vascular endothelial growth factor in foam cells by a water-soluble fraction of Polygonum multiflorum. J Pharmacol Sci 99: 294–300.
- Yang X, Hu W, Zhang Q, et al. 2010. Puerarin inhibits C-reactive protein expression via suppression of nuclear factor kappaB activation in lipopolysaccharide-induced peripheral blood mononuclear cells of patients with stable angina pectoris. Basic Clin Pharmacol Toxicol 107: 637–642.
- Yoshie F, Iizuka A, Kubo M, et al. 2001. Protective effects of Saiko-ka-ryukotsu-borei-to (Chai-Hu-Jia-Long-Gu-Mu-Li-Tang) against atherosclerosis in Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits. Pharmacol Res 43: 481–488.
- Yu YH, Xu XQ, Wang Y, et al. 2006. Intervention of Tongxinluo capsule against vascular lesion of atherosclerosis and its effect on lectin-like oxidized low density lipoprotein receptor-1 expression in rabbits. Chin J Integr Med 12: 32–36.
- Yu YM, Lin HC. 2010. Curcumin prevents human aortic smooth muscle cells migration by inhibiting of MMP-9 expression. Nutr Metab Cardiovasc Dis 20: 125–132.
- Yuan HY, Kuang SY, Zheng X, et al. 2008. Curcumin inhibits cellular cholesterol accumulation by regulating SREBP-1/caveolin-1 signaling pathway in vascular smooth muscle cells. Acta Pharmacol Sin 29: 555–563.
- Zhang L, Liu Y, Lu XT, et al. 2009a. Traditional Chinese medication Tongxinluo dose-dependently enhances stability of vulnerable plaques: a comparison with a high-dose simvastatin therapy. Am J Physiol Heart Circ Physiol 297, H2004–H2014.
- Zhang Q, Chang Z, Yang J, et al. 2008a. Antiatherogenic property of triterpenoids-enriched extract from the aerial parts of Salvia miltiorrhiza. Phytother Res 22: 1040–1045.
- Zhang W, Xu XL, Wang YQ, et al. 2009b. Effects of 2,3,4',5-tetrahydroxystilbene 2-O-beta-D-glucoside on vascular endothelial dysfunction in atherogenic-diet rats. Planta Med 75: 1209–1214.
- Zhang YG, Zhang HG, Zhang GY, et al. 2008b. Panax notoginseng saponins attenuate atherosclerosis in rats by regulating the blood lipid profile and an anti-inflammatory action. Clin Exp Pharmacol Physiol 35: 1238–1244.
- Zhou M, Xu H, Pan L, et al. 2008. Emodin promotes atherosclerotic plaque stability in fat-fed apolipoprotein E-deficient mice. Tohoku J Exp Med 215: 61–69.
- Zhou Z, Liu Y, Miao AD, et al. 2005. Salvianolic acid B attenuates plasminogen activator inhibitor type 1 production in TNF-alpha treated human umbilical vein endothelial cells. J Cell Biochem 96: 109–116.