The effects of Crataegus pinnatifida (Chinese hawthorn) on metabolic syndrome: A review

Document Type : Review Article


1 Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

2 Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran


Metabolic syndrome is described as a group of risk factors in which at least three unhealthy medical conditions, including obesity, high blood sugar, hypertension or dyslipidemia occur simultaneously in a patient. These conditions raise the risk for diabetes mellitus and cardiovascular diseases. Many recent studies have focused on herbal remedies and their pharmacological effects on metabolic syndrome. Crataegus pinnatifida or Chinese hawthorn has been widely used in the treatment of hyperlipidemia and cardiovascular diseases. Its leaves, fruits and seeds have various active substances such as, flavonoids, triterpenic acids and sesquiterpenes, which through different mechanisms can be beneficial in metabolic syndrome. Flavonoids found in the leaves of hawthorn can significantly reduce atherosclerotic lesion areas, the fruit extracts contain two triterpenic acids (oleanolic acid and ursolic acid), that have the ability to inhibit the acyl-coA-cholesterol acyltransferase (ACAT) enzyme and as a result reduce very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) cholesterol levels. Another example regards a sesquiterpene found in the seeds of C. pinnatifida, which exhibits the ability to inhibit platelet aggregation, thus showing antithrombotic activity. Various studies have shown that C. pinnatifida can have beneficial effects on controlling and treating high blood sugar, dyslipidemia, obesity and atherosclerosis. The aim of this review is to highlight the interesting effects of C. pinnatifida on metabolic syndrome.


Main Subjects

1. Smith CJ, Ryckman KK. Epigenetic and developmental influences on the risk of obesity, diabetes, and metabolic syndrome. Diabetes Metab Syndr Obes 2015; 8:295-302.
2. Yokozawa T, Kim HJ, Cho EJ. Gravinol ameliorates high-fructose-induced metabolic syndrome through regulation of lipid metabolism and proinflammatory state in rats. J Agric Food Chem 2008; 56:5026-5032.
3. Nagao K, Yanagita T. Bioactive lipids in metabolic syndrome. Prog Lipid Res 2008; 47:127-146.
4. Liu SH, He SP, Chiang MT. Effects of long-term feeding of chitosan on postprandial lipid responses and lipid metabolism in a high-sucrose-diet-impaired glucose-tolerant rat model. J Agric Food Chem 2012; 60:4306-4313.
5. Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 2010; 87:4-14.
6. Rother KI. Diabetes treatment--bridging the divide. N Engl J Med 2007; 356:1499-1501.
7. Gentile CL, Pagliassotti MJ. The role of fatty acids in the development and progression of nonalcoholic fatty liver disease. J Nutr Biochem 2008; 19:567-576.
8. 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.
9. Fasinu PS, Bouic PJ, Rosenkranz B. An overview of the evidence and mechanisms of herb-drug interactions. Front Pharmacol 2012; 3:69.
10. Razavi BM, Hosseinzadeh H. Saffron as an antidote or a protective agent against natural or chemical toxicities. Daru 2015; 23:31.
11. Dorri M, Hashemitabar S, Hosseinzadeh H. Cinnamon (Cinnamomum zeylanicum) as an antidote or a protective agent against natural or chemical toxicities: a review. Drug Chem Toxicol 2018: 41:338-351
12. Rameshrad M, Razavi BM, Hosseinzadeh H. Protective effects of green tea and its main constituents against natural and chemical toxins: A comprehensive review. Food Chem Toxicol 2017; 100:115-137.
13. Rouhi-Boroujeni H, Rouhi-Boroujeni H, Gharipour M, Mohammadizadeh F, Ahmadi S, Rafieian-Kopaei M. Systematic review on safety and drug interaction of herbal therapy in hyperlipidemia: a guide for internist. Acta Biomed 2015; 86:130-136.
14. Tabeshpour J, Razavi BM, Hosseinzadeh H. Effects of Avocado (Persea americana) on Metabolic Syndrome: A Comprehensive Systematic Review. Phytother Res 2017: 31:819-837
15. Razavi BM, Hosseinzadeh H. Saffron: a promising natural medicine in the treatment of metabolic syndrome. J Sci Food Agric 2017; 97:1679-1685.
16. Mollazadeh H, Hosseinzadeh H. Cinnamon effects on metabolic syndrome: a review based on its mechanisms. Iran J Basic Med Sci 2016; 19:1258-1270.
17. Sanati S, Razavi BM. A review of the effects of Capsicum annuum L. and its constituent, capsaicin, in metabolic syndrome.  Iran J Basic Med Sci  2018; 21:439-448.
18. Hosseini A, Hosseinzadeh H. A review on the effects of Allium sativum (Garlic) in metabolic syndrome. J Endocrinol Invest 2015; 38:1147-1157.
19. Akaberi M, Hosseinzadeh H. Grapes (Vitis vinifera) as a Potential Candidate for the Therapy of the Metabolic Syndrome. Phytother Res 2016; 30:540-556.
20. Xie W, Zhao Y, Du L. Emerging approaches of traditional Chinese medicine formulas for the treatment of hyperlipidemia. J Ethnopharmacol 2012; 140:345-367.
21. McGovern PE, Zhang J, Tang J, Zhang Z, Hall GR, Moreau RA, et al. Fermented beverages of pre- and proto-historic China. Proc Natl Acad Sci U S A 2004; 101:17593-17598.
22. Chen J, Xue B, Li K, Shi J, Krempin D, Zhu M, et al. The effects of an instant haw beverage on lipid levels, antioxidant enzyme and immune function in hyperlipidemia patients. Zhonghua Yu Fang Yi Xue Za Zhi 2002; 36:172-175.
23. Chang WT, Dao J, Shao ZH. Hawthorn: potential roles in cardiovascular disease. Am J Chin Med 2005; 33:1-10.
24. Zhang Z, Ho WK, Huang Y, James AE, Lam LW, Chen ZY. Hawthorn fruit is hypolipidemic in rabbits fed a high cholesterol diet. J Nutr 2002; 132:5-10.
25. Ogurtsova K, da Rocha Fernandes JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, et al. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract 2017; 128:40-50.
26. Goda T, Suruga K, Komori A, Kuranuki S, Mochizuki K, Makita Y, et al. Effects of miglitol, an alpha-glucosidase inhibitor, on glycaemic status and histopathological changes in islets in non-obese, non-insulin-dependent diabetic Goto-Kakizaki rats. Br J Nutr 2007; 98:702-710.
27. Wang T, An Y, Zhao C, Han L, Boakye-Yiadom M, Wang W, et al. Regulation effects of Crataegus pinnatifida leaf on glucose and lipids metabolism. J Agric Food Chem 2011; 59:4987-4994.
28. Tao W, Deqin Z, Yuhong L, Hong L, Zhanbiao L, Chunfeng Z, 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.
29. Xie W, Xing D, Zhao Y, Su H, Meng Z, Chen Y, et al. A new tactic to treat postprandial hyperlipidemia in diabetic rats with gastroparesis by improving gastrointestinal transit. Eur J Pharmacol 2005; 510:113-120.
30. Chowdhury SS, Islam MN, Jung HA, Choi JS. In vitro antidiabetic potential of the fruits of Crataegus pinnatifida. Res Pharm Sci 2014; 9:11-22.
31. Cordain L, Eades MR, Eades MD. Hyperinsulinemic diseases of civilization: more than just Syndrome X. Comp Biochem Physiol A Mol Integr Physiol 2003; 136:95-112.
32. Videla LA, Rodrigo R, Araya J, Poniachik J. Insulin resistance and oxidative stress interdependency in non-alcoholic fatty liver disease. Trends Mol Med 2006; 12:555-558.
33. Petta S, Muratore C, Craxi A. Non-alcoholic fatty liver disease pathogenesis: the present and the future. Dig Liver Dis 2009; 41:615-625.
34. Moller DE. New drug targets for type 2 diabetes and the metabolic syndrome. Nature 2001; 414:821-827.
35. Kelly JP, Kaufman DW, Kelley K, Rosenberg L, Anderson TE, Mitchell AA. Recent trends in use of herbal and other natural products. Arch Intern Med 2005; 165:281-286.
36. Liu J, Zhang H, Ji B, Cai S, Wang R, Zhou F, et al. A diet formula of Puerariae radix, Lycium barbarum, Crataegus pinnatifida, and Polygonati rhizoma alleviates insulin resistance and hepatic steatosis in CD-1 mice and HepG2 cells. Food Funct 2014; 5:1038-1049.
37. Aierken A, Buchholz T, Chen C, Zhang X, Melzig MF. Hypoglycemic effect of hawthorn in type II diabetes mellitus rat model. J Sci Food Agric 2017. 97:4557-4561.
38. Haslam DW, James WP. Obesity. Lancet 2005; 366:1197-1209.
39. Gurevich-Panigrahi T, Panigrahi S, Wiechec E, Los M. Obesity: pathophysiology and clinical management. Curr Med Chem 2009; 16:506-521.
40. Heck AM, Yanovski JA, Calis KA. Orlistat, a new lipase inhibitor for the management of obesity. Pharmacotherapy 2000; 20:270-279.
41. Bray GA. Drug treatment of obesity. Rev Endocr Metab Disord 2001; 2:403-418.
42. Ali AT, Hochfeld WE, Myburgh R, Pepper MS. Adipocyte and adipogenesis. Eur J Cell Biol 2013; 92:229-236.
43. Lee YH, Kim YS, Song M, Lee M, Park J, Kim H. A Herbal formula HT048, Citrus unshiu and Crataegus pinnatifida, prevents obesity by inhibiting adipogenesis and lipogenesis in 3T3-L1 preadipocytes and HFD-induced obese rats. Molecules 2015; 20:9656-9670.
44. Kuo DH, Yeh CH, Shieh PC, Cheng KC, Chen FA, Cheng JT. Effect of shanzha, a Chinese herbal product, on obesity and dyslipidemia in hamsters receiving high-fat diet. J Ethnopharmacol 2009; 124:544-550.
45. Wald NJ, Law MR. Serum cholesterol and ischaemic heart disease. Atherosclerosis 1995; 118 Suppl:S1-5.
46. Davidson P. Traditional Chinese Medicine and heart disease: what does Western medicine and nursing science know about it?  Eur J Cardiovasc Nurs 2003; 2:171-181.
47. Ridley BL, O’Neill MA, Mohnen D. Pectins: structure, biosynthesis, and oligogalacturonide-related signaling. Phytochemistry 2001; 57:929-967.
48. Lattimer JM, Haub MD. Effects of dietary fiber and its components on metabolic health. Nutrients 2010; 2:1266-1289.
49. Shinohara K, Ohashi Y, Kawasumi K, Terada A, Fujisawa T. Effect of apple intake on fecal microbiota and metabolites in humans. Anaerobe 2010; 16:510-515.
50. Li T, Li S, Dong Y, Zhu R, Liu Y. Antioxidant activity of penta-oligogalacturonide, isolated from haw pectin, suppresses triglyceride synthesis in mice fed with a high-fat diet. Food Chem 2014; 145:335-341.
51. Lin Y, Vermeer MA, Trautwein EA. Triterpenic acids present in hawthorn lower plasma cholesterol by inhibiting intestinal acat activity in hamsters. Evid Based Complement Alternat Med 2011; 2011:801272.
52. Goldstein JL, Brown MS. Regulation of the mevalonate pathway. Nature 1990; 343:425-430.
53. Ye XL, Huang WW, Chen Z, Li XG, Li P, Lan P, et al. Synergetic effect and structure-activity relationship of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors from Crataegus pinnatifida Bge. J Agric Food Chem 2010; 58:3132-3138.
54. Hu M, Zeng W, Tomlinson B. Evaluation of a crataegus-based multiherb formula for dyslipidemia: a randomized, double-blind, placebo-controlled clinical trial. Evid Based Complement Alternat Med 2014; 2014.
55. Luo Y, Chen G, Li B, Ji B, Xiao Z, Yi G, et al. Dietary intervention with AHP, a functional formula diet, improves both serum and hepatic lipids profile in dyslipidemia mice. J Food Sci 2009; 74: 189-195.
56. Seals DR, Jablonski KL, Donato AJ. Aging and vascular endothelial function in humans. Clin Sci (Lond) 2011; 120:357-375.
57. Yoo JH, Liu Y, Kim HS. Hawthorn fruit extract elevates expression of Nrf2/HO-1 and improves lipid profiles in ovariectomized rats. Nutrients 2016; 8.
58. Signorelli SS, Neri S, Sciacchitano S, Pino LD, Costa MP, Marchese G, et al. Behaviour of some indicators of oxidative stress in postmenopausal and fertile women. Maturitas 2006; 53:77-82.
59. Stachowiak G, Pertynski T, Pertynska-Marczewska M. Metabolic disorders in menopause. Prz Menopauzalny 2015; 14:59-64.
60. Niu C, Chen C, Chen L, Cheng K, Yeh C, Cheng J. Decrease of blood lipids induced by Shan-Zha (fruit of Crataegus pinnatifida) is mainly related to an increase of PPARalpha in liver of mice fed high-fat diet. Horm Metab Res 2011; 43:625-630.
61. Kwok C-Y, Li C, Cheng H-L, Ng Y-F, Chan T-Y, Kwan Y-W, et al. Cholesterol lowering and vascular protective effects of ethanolic extract of dried fruit of Crataegus pinnatifida, hawthorn (Shan Zha), in diet-induced hypercholesterolaemic rat model. J Funct Foods 2013; 5:1326-1335.
62. Kwok C-Y, Wong CN-Y, Yau MY-C, Yu PH-F, Au ALS, Poon CC-W, et al. Consumption of dried fruit of Crataegus pinnatifida (hawthorn) suppresses high-cholesterol diet-induced hypercholesterolemia in rats. J Funct Foods 2010; 2:179-186.
63. Chen JD, Wu YZ, Tao ZL, Chen ZM, Liu XP. Hawthorn (shan zha) drink and its lowering effect on blood lipid levels in humans and rats. World Rev Nutr Diet 1995; 77:147-154.
64. Weber C, Noels H. Atherosclerosis: current pathogenesis and therapeutic options. Nat Med 2011; 17:1410-1422.
65. Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature 2011; 473:317-325.
66. Zhang J, Liang R, Wang L, Yan R, Hou R, Gao S, et al. Effects of an aqueous extract of Crataegus pinnatifida Bge. var. major N.E.Br. fruit on experimental atherosclerosis in rats. J Ethnopharmacol 2013; 148:563-569.
67. Dong P, Pan L, Zhang X, Zhang W, Wang X, Jiang M, et al. Hawthorn (Crataegus pinnatifida Bunge) leave flavonoids attenuate atherosclerosis development in apoE knock-out mice. J Ethnopharmacol 2017; 198:479-488.
68. Zhou CC, Huang XX, Gao PY, Li FF, Li DM, Li LZ, et al. Two new compounds from Crataegus pinnatifida and their antithrombotic activities. J Asian Nat Prod Res 2014; 16:169-174.
69. Li L-Z, Gao P-Y, Song S-J, Yuan Y-Q, Liu C-T, Huang X-X, et al. Monoterpenes and flavones from the leaves of Crataegus pinnatifida with anticoagulant activities. J Funct Foods 2015; 12:237-245.