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Hawthorn (Crataegus monogyna, Crataegus oxyacantha)

Hawthorn (Crataegus monogyna, Crataegus oxyacantha) is a member of Rosaceae family and has been recorded as a popular medicinal plant in most of the countries. The berry has been a key part of traditional Chinese medicine for at least 2000 years. The genus name, “Crataegus” comes from the Greek word, “kràtaigos” which means “strength and robustness” due to its hard and durable wood. The parts of the Hawthorn bush that are used for medicinal purposes are the berries and the leaf. The berries of the Hawthorn are collected in the fall after they turn a dark purple.

Hawthorn berries are one of the oldest known medicinal plants used in European herbal medicine. Dioscorides, a Greek herbalist, was the first to report the performance of Hawthorn Berry on the heart. Dioscorides was followed by a Swiss physician, Paracelsus who touted the use of Hawthorn Berry for its actions on the heart. During his years of practice, Dr. Green of Ennis, Ireland held such a reputation of curing heart disease and other ailments of the heart, that he had patients from all over the United Kingdom. While remaining a physician in good standing, he refused to share his secret with his colleagues. After his death in 1894, Dr. Green’s daughter revealed that a concentrate of fresh Hawthorn berries, Crataegus Oxycantha, Common Hawthorn, was the formula which her father had successfully used to cure his many heart patients.

Hawthorn (Crataegus monogyna, Crataegus oxyacantha)

Usos

It is used in traditional Chinese medicine to improve digestion, stimulate appetite, treat cardiovascular conditions and hyperlipidemia, and invigorate blood. Hawthorn extract also has a long history in European medicine as a cardiotonic. Because of Hawthorn Berry’s anti-inflammatory properties, it has been used to reduce ulcerative colitis, also known as inflammatory bowel disease. When used for weight loss, it aids in digestion and helps reduce water retention by expelling excess salt from the body. Hawthorn is also high in pectin and therefore is soothing to the throat and respiratory tract. Hawthorn Berry is known to reduce nervous tension and alleviate insomnia.
Hawthorn is currently used extensively by physicians in Europe in its standardized form for early stage of heart failure and various other cardiovascular and peripheral circulatory conditions including angina, cardiac incompetence not yet requiring digitalis, hypertension, and arrhythmias.

Química/Farmacología

Chemical analysis has allowed for the identification of more than 150 bioactive molecules in Hawthorn fruits, leaves, and flowers, such as flavonoids, oligomeric proanthocyanidins, triterpene acids, phenolic acids (ferulic, gallic, p-coumaric, syringic, chlorogenic organic acids (fumaric, tartaric, succinic, citric, malic), sterols, sugars (maltose, sucrose, glucose, fructose) and trace amounts of cardioactive amines. Flavonoids and OPCs are the two major groups of bioactive components. Pharmacologic activities of hawthorn flower, leaf, and berry extracts are attributed to constituents such as flavonoids and oligomeric procyanidins. Laboratory experiments suggest cardiac action of the flavonoids occurs via inhibition of the 3’,5’-cyclic adenosine monophosphate phosphodiesterase, and demonstrate positive inotropic effects by hawthorn that increase heart rate. Inotropic and vasodilatory effects have also been related to increased myocardial perfusion and reduced afterload. Antioxidant properties and inhibitory effects against LDL oxidation are attributed to phenolic compounds.

Estudios clínicos

Various animal studies have suggested that hawthorn extracts exert a wide range of pharmacological properties, especially on the cardiovascular system, including cardiotonic, antiarrhythmic, hypotensive, hypolipidemic, and antioxidant activities.

Cardiotonic Activity

Numerous in vitro and animal studies have tested the activities of water-soluble extract, flavonoid fraction, triterpene fraction, and OPC fraction, which are prepared from hawthorn fruits, leaves, or flowers as well as individual components of hawthorn (hyperoside, luteolin-7-glucoside, epicatechin, vitexin, and rutin). Marked cardiotonic actions have been observed: positive inotropic and negative chronotropic effect, increase of coronary blood flow and cardiac output, and reduction of oxygen consumption. These actions may be related to phosphodiesterase inhibitory effect.

Hypolipidemic Activity

Hawthorn has been found to decrease the serum levels of cholesterol, LDL-cholesterol, and triglyceride in hypercholesterolemic and atherosclerotic animals. It also significantly inhibits lipid deposition in the liver and aorta. When administered to rats fed with an atherogenic diet, the hawthorn fruit extract increased excretion of bile acid, depressed hepatic cholesterol synthesis, and significantly increased the binding of 125I-LDL to the liver plasma membranes, indicating an enhancement of the LDL-receptor activity.
Hypotensive Activity

When flavonoid, OPC, and triterpene acid extracts were administrated intravenously to various species of animals, prolonged dose-dependent hypotension in anaesthetized normotensive and hypertensive animals was observed. The hypotensive action was mainly attributed to peripheral vasodilation. In more recent studies, the hawthorn extract was found to induce endothelium-dependent relaxation in an isolated rat mesenteric artery. Procyanidins were identified as the major component for this effect.

Antiarrhythmic Activity

The cardiovascular effects described for hawthorn extract is somewhat like that of phosphodiesterase-3 (PDE3) inhibitors, which demonstrate various pharmacological properties including cardio-medicinal, vasodilating, anti-inflammatory and antioxidant, and have been identified as potential therapeutic agents in cardiovascular disease. However, Hawthorn extracts show unique chronotropic effects that it appears to be antiarrhythmic, but capable of inducing rhythmicity in quiescent cardiomyocytes, suggesting Hawthorn extracts may contain unique PDE3 inhibitors without arrhythmogenic potential.

Mecanismo biomecánico

The primary activity of hawthorn is to increase coronary blood flow. This may be due to relaxation of coronary arteries, which directly increases blood flow or through an increase in contraction and relaxation velocities, which increases the diastolic interval and thus allows more time for blood passage through the coronary arteries.

Hawthorn’s positive inotropic action may also be due to inhibition of myocardial Na+/K+ ATPase which is an integral membrane enzyme that maintains cardiac resting potential. It also decreases blood pressure which results in an increase in exercise tolerance during the early stage of congestive heart failure (CHF). Surprisingly, Hawthorn can regulate both low and high blood pressure. With the bioflavonoids reportedly dilating both peripheral and coronary blood vessels leading to its use in angina; the procyanidins content is claimed to support the vasorelaxant effects. Hawthorn’s glycoside component has also been reported to increase vagal tone of the heart.

Hawthorn has also been reported to have angiotensin converting enzyme (ACE) inhibiting effect. It may also have a cardio-protective effect due to its ability to decrease the oxygen demands of cardiac tissue. Varying results have been observed regarding the effect of hawthorn and its constituents on heart rate. In majority of in vitro studies, an increase in heart rate has been observed while conversely, most in vivo studies report a decrease in heart rate.

Hawthorn has been shown to exhibit antioxidant activity associated with its flavonoid and procyanidin content. Hawthorn also exhibits anti-inflammatory property by preventing synthesis and release of inflammatory promoters such as histamines, serine proteases, prostaglandins, leukotrienes etc. as well as inhibiting enzymatic cleavage by enzyme secreted by leukocytes during inflammation.

Fuentes/Artículos

Al Makdessi,. Sweidan, S. Müllner, and R. Jacob. "Myocardial protection by pretreatment with Crataegus oxyacantha: an assessment by means of the release of lactate dehydrogenase by the ischemic and reperfused Langendorff heart." Arzneimittel-forschung 46, no. 1 (1996): 25-27. https://europepmc.org/article/med/8821513

Al Makdessi, Sweidan, H. Sweidan, K. Dietz, and R. Jacob. "Protective effect of Crataegus oxyacantha against reperfusion arrhythmias after global no-flow ischemia in the rat heart." Basic research in cardiology 94, no. 2 (1999): 71-77. https://link.springer.com/article/10.1007/s003950050128

Attard, Everaldo, and Henrietta Attard. "The potential angiotensin-converting enzyme inhibitory activity of oleanolic acid in the hydroethanolic extract of Crataegus monogyna Jacq." Natural Product Communications 1, no. 5 (2006): 1934578X0600100507. https://journals.sagepub.com/doi/pdf/10.1177/1934578X0600100507

Blesken, R. "Crataegus in cardiology." Fortschritte der Medizin 110, no. 15 (1992): 290-292. https://europepmc.org/article/med/1634169

Bödigheimer, K., and D. Chase. "Effectiveness of hawthorn extract at a dosage of 3 x 100 mg per day. Multicentre double-blind trial with 85 NYHA stage II heart failure patients." Muenchener Medizinische Wochenschrift 136 (1994).

Chang, Qi, Zhong Zuo, Francisco Harrison, and Moses Sing Sum Chow. "Hawthorn." The Journal of Clinical Pharmacology 42, no. 6 (2002): 605-612.

Dahmer S, Scott E. Health effects of hawthorn. Am Fam Physician. Feb 15 2010;81(4):465-468.

Degenring FH, Suter A, Weber M, Saller R. A randomised double blind placebo controlled clinical trial of a standardised extract of fresh Crataegus berries (Crataegisan) in the treatment of patients with congestive heart failure NYHA II. Phytomedicine. 2003;10(5):363-9.

Eiff, M. Von, H. Brunner, A. Haegeli, U. Kreuter, B. Martina, B. Meier, and W. Schaffner. "Hawthorn/passion flower extract and improvement in physical exercise capacity of patients with dyspnoea class II of the NYHA functional classification." Acta Therapeutica 20, no. 1 (1994): 47.

Elango, Chinnasamy, and Sivasithambaram Niranjali Devaraj. "Immunomodulatory effect of Hawthorn extract in an experimental stroke model." Journal of neuroinflammation 7, no. 1 (2010): 1-13. https://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-7-97

Gildor A. Crataegus oxyacantha and heart failure. Circulation 1998;98:2098.

Holubarsch CJ, Colucci WS, Meinertz T, et al. The efficacy and safety of Crataegus extract WS 1442 in patients with heart failure: the SPICE trial. Eur J Heart Fail. Dec 2008;10(12):1255-1263.

Iwamoto M, Sato T, Ishizaki T. Klinische Wirkung von Crataegutt bei Herzerkrankungen ischaemischer und/oder hypertensiver Genese. Planta Med 1981;42:1-16.

Nasa, Y., H. Hashizume, A. N. Hoque, and Y. Abiko. "Protective effect of Crataegus extract on the cardiac mechanical dysfunction in isolated perfused working rat heart." Arzneimittel-forschung 43, no. 9 (1993): 945-949. https://europepmc.org/article/med/8240455

Pittler M, Guo R, Ernst E. Hawthorn extract for treating chronic heart failure. Cochrane Database Syst Rev 2008;(1):CD005312.

Pöpping, S., H. Rose, I. Ionescu, Y. Fischer, and H. Kammermeier. "Effect of a hawthorn extract on contraction and energy turnover of isolated rat cardiomyocytes." Arzneimittel-forschung 45, no. 11 (1995): 1157-1161. https://europepmc.org/article/med/8929230

Rajendran, Shanthi, P. D. Deepalakshmi, K. Parasakthy, H. Devaraj, and S. Niranjali Devaraj. "Effect of tincture of Crataegus on the LDL-receptor activity of hepatic plasma membrane of rats fed an atherogenic diet." Atherosclerosis 123, no. 1-2 (1996): 235-241.
https://www.sciencedirect.com/science/article/abs/pii/0021915096058133

Ranjbar K, Zarrinkalam E, Salehi I, et al. Cardioprotective effect of resistance training and Crataegus oxyacantha extract on ischemia reperfusion-induced oxidative stress in diabetic rats. Biomed

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Schmidt U, et al. Efficacy of the hawthorn preparation in 78 patients with chronic congestive heart failure defined as NYHA functional class II. Phytomedicine 1994;1:17-24.

Schussler M, Holzl J, Fricke U. Myocardial effects of flavonoids from Crataegus species. Arzneimittelforschung 1995;45:843-5.

Shanthi, S., K. Parasakthy, P. D. Deepalakshmi, and S. Niranjali Devaraj. "Hypolipidemic activity of tincture of Crataegus in rats." Indian Journal of Biochemistry & Biophysics 31, no. 2 (1994): 143-146. https://europepmc.org/article/med/7927437

Tadiæ VM, Dobriæ S, Markoviæ GM, et la. Anti-inflammatory, gastroprotective, free-radical-scavenging, and antimicrobial activities of hawthorn berries ethanol extract. J Agric Food Chem. 2008 Sep 10;56(17):7700-9.

Tassell, Mary C., Rosari Kingston, Deirdre Gilroy, Mary Lehane, and Ambrose Furey. "Hawthorn (Crataegus spp.) in the treatment of cardiovascular disease." Pharmacognosy reviews 4, no. 7 (2010): 32. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249900/

Tauchert M. Efficacy and safety of Crataegus extract WS 1442 in comparison with placebo in patients with chronic stable New York Heart Association class-III heart failure. Am Heart J. May 2002;143(5):910-915.

Tauchert, M., A. Gildor, and J. Lipinski. "High-dose Crataegus extract WS 1442 in the treatment of NYHA stage II heart failure." Herz 24, no. 6 (1999): 465-74. https://europepmc.org/article/med/10546150

Walker, AF, et al. Promising hypotensive effect of hawthorn extract: a randomized double-blind pilot study of mild, essential hypertension. Phytotherapy Res 2002;16:48-54.

Walker AF, Marakis G, Simpson E, et al. Hypotensive effects of hawthorn for patients with diabetes taking prescription drugs: a randomised controlled trial. Br J Gen Pract 2006;56(527):437-43.

Wang J, Xiong X, Feng B. Effect of Crataegus usage in cardiovascular disease prevention: an evidence-based approach. Evid Based Complement Alternat Med. 2013;2013:149363.

Xu Y, Zhang Y, Zhou F, et al. Human pregnane X receptor-mediated transcriptional regulation of CYP3A4 by extracts of 7 traditional Chinese medicines. Zhongguo Zhong Yao Za Zhi. 2011 Jun;36(11):1524-7.
Yang, Baoru, and Pengzhan Liu. "Composition and health effects of phenolic compounds in hawthorn (Crataegus spp.) of different origins." Journal of the Science of Food and Agriculture 92, no. 8 (2012): 1578-1590. https://d1wqtxts1xzle7.cloudfront.net/50611626/jsfa.567120161129-12912-1ov5vat-with-cover-page-v2.pdf?Expires=1650566171&Signature=aaeSpSgt7WwJDHDl9-oOC~COmJL4b4n6yxOpKaWUDP4As37kmtT699jq-GWIALM4NC~tEyUNA3b9Uiuo5FDwfyyqDbNVCjZ8rGR4VOEq1tR6eFrhv27uCSDPVrQrwnePSTmgAFFKNpn7abdkBUy0XVe79hWl5lMX3WIaCxzUgOGKqkKRHbD4SUFWtBZAND2kvucZRk44-Usuo3o5QYcIQGQXURv3jdROgo-340VynbtbqBS2LdxFScP4EyXPY4etN4Tmo6-nPxm2JVOvjBsfKTECB5KJtkOEBoQ0JVwWAIjdmSG5kv8G5eUNqy6KfpDnBsRCZXx7mhOFK2SLP-t1nw__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA

Zhang, Zesheng, Walter KK Ho, Y. U. Huang, Anthony E. James, Lik Wang Lam, and Zhen-Yu Chen. "Hawthorn fruit is hypolipidemic in rabbits fed a high cholesterol diet." The Journal of nutrition 132, no. 1 (2002): 5-10. https://academic.oup.com/jn/article/132/1/5/4768395

Zick SM, Vautaw BM, Gillespie B, et al. Hawthorn Extract Randomized Blinded Chronic Heart Failure (HERB CHF) trial. Eur J Heart Fail. Oct 2009;11(10):990-999.

Zick SM, Gillespie B, Aaronson KD. The effect of Crataegus oxycantha Special Extract WS 1442 on clinical progression in patients with mild to moderate symptoms of heart failure. Eur J Heart Fail. Jun 2008;10(6):587-593.

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