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Hawthorn Research
Hawthorn is best known for its helpful effects on the heart. Hawthorn provides cardiovascular protection. It also supposedly helps when you have a heart condition. Hawthorn has been also been used for the treatment of digestive ailments, dyspnea,and kidney stones. There is also indications that is has antiviral and antioxidant activity, besides possible anxiety reducing properties. Please read the current research. It is easiest if you just read the conclusions.
Forsch Komplementarmed Klass Naturheilkd. 2004;11 Suppl 1:36-9. : Prospective, Comparative Cohort Studies and Their Contribution to the Benefit Assessments of Therapeutic Options: Heart Failure Treatment with and without Hawthorn Special Extract WS 1442.
Habs M.
Dr. Willmar Schwabe GmbH and Co. KG, Karlsruhe, Germany.

Background : In addition to testing a drug for its efficacy, pharmacological quality and safety, current policies are increasingly demanding evaluations of the therapeutic benefits provided by a drug in general practice with 'non-selected' patients and increasingly restrictive economic considerations. Objective : One of the trials which addresses this task is the WISO cohort study (Efficacy and socio-economic relevance of treatment of chronic heart failure stage NYHA II with Crataegus extract WS((R)) 1442). It compares two different therapeutic strategies in the treatment of heart failure stage NYHA II, i.e. a conventional medication and a therapy which also includes hawthorn special extract WS((R)) 1442 (Crataegutt((R)) novo 450) in addition to chemical-synthetic drugs. In contrast to clinical trials, the patients in cohort studies are expressly not randomised and the physician in charge independently choses the administered treatment. This comparative, non-interventional observation provides well-founded evidence of the 'real-world effectiveness' of the tested preparation. Patients and Methods : 952 patients with heart failure (NYHA II) were enrolled in the study by 217 general practitioners. 588 patients received Crataegus special extract WS((R)) 1442 (Crataegutt((R)) novo 450) either as an add-on therapy or as a monotherapy (Crataegus cohort) and 364 patients received therapy without hawthorn (comparative cohort). These two groups had the same indication (heart failure NYHA II) but were significantly different regarding gender, age and concomitant cardiovascular disease. Basically, in view of the free choice of therapy made by the physician in charge, such differences are to be expected in comparative observational studies. A sufficient degree of patient comparability was provided by means of the matched-pairs technique, which replaced the randomisation procedure normally used in clinical studies. After 2 years, 130 patient pairs generated by this technique could be included in the interim assessment. Results : The clinical symptoms with regard to all parameters investigated showed the same or a more pronounced improvement in the Crataegus cohort in the course of 2 years. After 2 years, the three cardinal symptoms of heart failure - fatigue (p = 0.036), stress dyspnoea (p = 0.020) and palpitations (p = 0.048) - were significantly less marked in the Crataegus cohort than in the comparative cohort. Discussion : The particular design of the cohort study also provides valuable additional information: (1) Hawthorn special extract WS((R)) 1442 was prescribed in registered cardiological practices for the treatment of patients with heart failure stage NYHA II, partly as an alternative and partly as a supplement to the used chemical-synthetic drugs. (2) Favourable effects on the clinical symptoms were achieved although the patients in the Crataegus cohort received markedly fewer chemical-synthetic drugs than the patients in the comparative cohort (ACE-inhibitors: 36 vs. 54%, p = 0.004; cardiac glycosides: 18 vs. 37%, p = 0.001; diuretics: 49 vs. 61%, p = 0.061; beta-blockers: 22 vs. 33%, p = 0.052). Conclusion : The data show a clear benefit for patients with heart failure stage NYHA II treated with WS((R)) 1442. The single or addon administration in addition to a chemical-synthetic medication resulted in objective improvements at comparable costs. Copyright 2004 S. Karger GmbH, Freiburg

J Neurochem. 2004 Jul;90(1):211-9. : Oral administration of Crataegus flavonoids protects against ischemia/reperfusion brain damage in gerbils.
Zhang DL, Zhang YT, Yin JJ, Zhao BL.
Laboratory of Visual Information Processing, Center for Brain and Cognitive Sciences, Institute of Biophysics, Academia Sinica, Beijing, China.

Stroke is the third leading cause of death as dementia is a main symptom of Alzheimer's disease. One of the important mechanisms in the pathogeny of stroke is free radical production during the reperfusion period, therefore the effects of a type of natural antioxidant, i.e. Crataegus flavonoids (CF), on brain ischemic insults were investigated in Mongolian gerbil stroke model. Results showed that pretreatment of the animals with CF decreased reactive oxygen species (ROS) production, thiobarbituric acid reactive substances content, and nitrite/nitrate concentration in brain homogenate, increased the brain homogenate-associated antioxidant level in a dose-dependent manner. CF pretreatment increased the amount of biologically available NO by scavenging of superoxide anion produced during reperfusion. At same time, in the process of ischemia/reperfusion brain damage, the content of nitrite/nitrate (the end product of NO) increased, and of NO detected by ESR decreased. Oral pretreatment with CF decreased the nitrite/nitrate content in the brain homogenate and increased the biologically available NO concentration in a dose-dependent manner. The increasing effect of antioxidant on NO might be due to its scavenging effect on superoxide anion, which could react with NO into peroxynitrite. iNOS was implied in delayed neuron death after brain ischemic damage and it was found that pretreatment with CF could decrease the protein level of tumor necrosis factor (TNF)-alpha and nuclear factor-kappa B (NF-kappaB), and increase the mRNA level of NOS estimated by western blotting and RT-PCR. More neurons survived and fewer cells suffered apoptosis in the hippocampal CA1 region of CF treated animal brain. These results suggest that oral administration of this antioxidant increases the antioxidant level in the brain and protects the brain against delayed cell death caused by ischemia/reperfusion injury

J Pharm Pharmacol. 2004 Jul;56(7):921-6. : Cardioprotective effect of tincture of Crataegus on isoproterenol-induced myocardial infarction in rats.
Jayalakshmi R, Niranjali Devaraj S.
Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600 025, India.

Tincture of Crataegus (TCR), an alcoholic extract of the berries of hawthorn (Crataegus oxycantha), is used in herbal and homeopathic medicine. The present study was done to investigate the protective effect of TCR on experimentally induced myocardial infarction in rats. Pretreatment of TCR, at a dose of 0.5 mL/100 g bodyweight per day, orally for 30 days, prevented the increase in lipid peroxidation and activity of marker enzymes observed in isoproterenol-induced rats (85 mg kg(-1) s. c. for 2 days at an interval of 24 h). TCR prevented the isoproterenol-induced decrease in antioxidant enzymes in the heart and increased the rate of ADP-stimulated oxygen uptake and respiratory coupling ratio. TCR protected against pathological changes induced by isoproterenol in rat heart. The results show that pretreatment with TCR may be useful in preventing the damage induced by isoproterenol in rat heart

Rev Enferm. 2004 Mar;27(3):8-12. : [States of nervousness. Useful medicinal plants]
[Article in Spanish]
Alonso Osorio MJ.

The author analyzes the effects of diverse medicinal plants such as poppy (papaver somniferum), Hawthorn, hypericum, and hops on those moderate nervous states which provoke insomnia, anxiety, or excitement as a complementary method to aid a patient overcome those states.

Life Sci. 2004 Feb 27;74(15):1945-55. : Crataegus special extract WS 1442 improves cardiac function and reduces infarct size in a rat model of prolonged coronary ischemia and reperfusion.
Veveris M, Koch E, Chatterjee SS.
Department of Medicinal Chemistry, Latvian Institute of Organic Synthesis, Riga, Latvia.

In Germany, hydroalcoholic extracts from hawthorn (Crataegus spp.) leaves with flowers are approved drugs for the treatment of mild forms of heart insufficiency. Besides cardiotonic effects these herbal remedies have been shown to possess cardioprotective properties. We now evaluated if treatment of rats with the Crataegus special extract WS 1442 also improves cardiac function and prevents myocardial infarction during prolonged ischemia and reperfusion lasting for 240 and 15 min, respectively. Oral administration of WS 1442 (10 or 100 mg x kg(-1) x day(-1)) for 7 days before ligation of the left coronary artery dose-dependently suppressed the decrease of the pressure rate product. WS 1442 treatment also attenuated the elevation of the ST-segment in the ECG, diminished the incidence of ventricular fibrillations (control: 67%; 10 mg x kg(-1): 64%; 100 mg x kg(-1): 27%) and reduced the mortality rate (control: 47%; 10 mg.kg(-1): 27%; 100 mg x kg(-1): 9%). Furthermore, the area of myocardial infarction within the ischemic zone was significantly smaller in treated rats (10 mg x kg(-1): 64.3 +/- 5.1%; 100 mg x kg(-1): 42.8 +/- 4.1%) when compared with controls (78.4 +/- 2.6%). It is suggested that these pharmacological effects are accounted for by the combined antioxidative, leukocyte elastase inhibiting and endothelial nitric oxide (NO) synthesis enhancing properties of WS 1442.

J Agric Food Chem. 2003 Dec 17;51(26):7583-8. : Inhibitory effect of hot-water extract from dried fruit of Crataegus pinnatifida on low-density lipoprotein (LDL) oxidation in cell and cell-free systems.
Chu CY, Lee MJ, Liao CL, Lin WL, Yin YF, Tseng TH.
School of Applied Chemistry, College of Health Management, and Institute of Biochemistry, College of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Chien Kuao N. Road, Taichung, 402 Taiwan.

The dried fruit of Crataegus pinnatifida, a local soft drink material and medical herb, was found to possess potential against oxidative stress. In the preliminary study, the antioxidant potential of a hot-water extract obtained from the dried fruit of C. pinnatifida (CF-H) was evaluated in terms of its capacity of quenching 1,1-diphenyl-2-picrylhydrazyl free radicals (EC(50) = 0.118 mg/mL). After content analysis, it was found that CF-H is mainly composed of polyphenols including flavonoids (6.9%), procyanidins (2.2%), (+)-catechin (0.5%), and (-)-epicatechin (0.2%). The antioxidative bioactivity of CF-H had been assess previously using the models of CuSO(4) as cell-free system and sodium nitroprusside (SNP) plus macrophage RAW 264.7 cells as cell system to induce human low-density lipoprotein oxidation. CF-H was found to inhibit relative electrophoretic mobility and thiobarbituric acid reactive substances at the concentration of 0.5-1.0 mg/mL in the cell-free system and at 0.01-0.10 mg/mL in the cell system. Furthermore, it was found that CF-H decreased the SNP-induced cell lipid peroxidation and reduced glutathione depletion.

Pharmazie. 2003 Aug;58(8):577-81. : Hawthorn extracts inhibit LDL oxidation.
Quettier-Deleu C, Voiselle G, Fruchart JC, Duriez P, Teissier E, Bailleul F, Vasseur J, Trotin F.
Laboratoire de Pharmacognosie, Faculte de Pharmacie, Institut Pasteur, Lille, France.

Polyphenol-rich diet decreases cardiovascular risk. LDL oxidation is the primary event in atherosclerosis plaque formation and antioxidants such as polyphenols were shown to inhibit LDL oxidation and atherosclerosis development. Hawthorn (Crataegus) and derived pharmaceuticals are rich in polyphenols and already prescribed to treat moderate heart failure, nervousness and sleep disorders. Extracts either from fresh plant parts (flower buds, flowers, young leaves or green fruits) or from dried pharmaceutical parts (flowers and flowering tops) were previously shown to be effective inhibitors of lipoperoxidation and scavengers of oxygen species. In this study, the capacity of total and ethyl-acetate extracts from dried pharmaceutical flowers, tops and fruits to inhibit Cu(2+)-induced LDL oxidation was tested. This capacity was positively linked to their content in total polyphenols, proanthocyanidins (global and oligomeric forms), as well as to their content in two individual phenolics: a flavanol, the dimeric procyanidin B2 and a flavonol glycoside, hyperoside. Flavanol-type phenolics showed to be higher active than the majority of the flavonoids tested in inhibiting Cu(2+)-induced LDL peroxidation. This study suggests that hawthorn could be a source of polyphenols able to inhibit LDL oxidation.

Am J Med. 2003 Jun 1;114(8):665-74. : Comment in: Am J Med. 2003 Jun 1;114(8):700-1. Am J Med. 2003 Nov;115(7):585; author reply 585-6.
Hawthorn extract for treating chronic heart failure: meta-analysis of randomized trials.
Pittler MH, Schmidt K, Ernst E.
Complementary Medicine, Peninsula Medical School, Universities of Exeter and Plymouth, 25 Victoria Park Road, Exeter EX2 4NT, United Kingdom.
M.H.Pittler@exeter.ac.uk

The aim of this meta-analysis was to assess the evidence from rigorous clinical trials of the use of hawthorn extract to treat patients with chronic heart failure. We searched the literature using MEDLINE, EMBASE, the Cochrane Library, CINAHL, CISCOM, and AMED. Experts on and manufacturers of commercial preparations containing hawthorn extract were asked to contribute published and unpublished studies. There were no restrictions about the language of publication. Two reviewers independently performed the screening of studies, selection, validation, data extraction, and the assessment of methodological quality. To be included, studies were required to state that they were randomized, double-blind, and placebo controlled, and used hawthorn extract monopreparations. Thirteen trials met all inclusion criteria. In most of the studies, hawthorn was used as an adjunct to conventional treatment. Eight trials including 632 patients with chronic heart failure (New York Heart Association classes I to III) provided data that were suitable for meta-analysis. For the physiologic outcome of maximal workload, treatment with hawthorn extract was more beneficial than placebo (weighted mean difference, 7 Watt; 95% confidence interval [CI]: 3 to 11 Watt; P < 0.01; n = 310 patients). The pressure-heart rate product also showed a beneficial decrease (weighted mean difference, -20; 95% CI: -32 to -8; n = 264 patients) with hawthorn treatment. Symptoms such as dyspnea and fatigue improved significantly with hawthorn treatment as compared with placebo. Reported adverse events were infrequent, mild, and transient; they included nausea, dizziness, and cardiac and gastrointestinal complaints. In conclusion, these results suggest that there is a significant benefit from hawthorn extract as an adjunctive treatment for chronic heart failure.

Eur J Heart Fail. 2003 Jun;5(3):319-26. : Efficacy of a homeopathic Crataegus preparation compared with usual therapy for mild (NYHA II) cardiac insufficiency: results of an observational cohort study.
Schroder D, Weiser M, Klein P.
Borsenstrasse 17, Frankfurt/Main, Germany.

OBJECTIVES: To compare the efficacy of the homeopathic Crataegus preparation Cralonin for non-inferiority to standard treatment for mild cardiac insufficiency. METHODS: Multicentre non-randomised cohort study in patients aged 50-75 years in New York Heart Association class II. Patients received Cralonin (n=110) or ACE inhibitor/diuretics (n=102) for 8 weeks. To adjust for confounding by baseline factors, populations were stratified according to propensity score. After adjusting, there were no statistically significant differences between treatment groups. Treatment efficacy was assessed on 15 variables. A stringent non-inferiority criterion for the upper limit of the 97.5% one-sided confidence interval of the treatment difference was set to 0.2x the standard deviation (S.D.). RESULTS: Both treatment regimens improved scores on most variables studied, with the greatest effect on double product after exercise (average score reduction 15.4% with Cralonin vs. 16.0% for the control group). Stringent non-inferiority of Cralonin was demonstrated on 7 variables. Medium-stringent (0.5xS.D.) non-inferiority was indicated by 13 variables (exceptions: systolic blood pressure (BP) during exercise and diastolic BP at rest; for these, differences between treatments were not significant). Both treatments were well tolerated. CONCLUSION: The Crataegus-based preparation Cralonin is non-inferior to usual ACE inhibitor/diuretics treatment for mild cardiac insufficiency on all parameters except BP reduction.

J Clin Pharmacol. 2003 Jun;43(6):637-42. : Interaction study between digoxin and a preparation of hawthorn (Crataegus oxyacantha).
Tankanow R, Tamer HR, Streetman DS, Smith SG, Welton JL, Annesley T, Aaronson KD, Bleske BE.
University of Michigan College of Pharmacy, University of Michigan Health Systems, Ann Arbor, Michigan, USA.

Hawthorn, an herbal supplement, is currently being evaluated for the treatment of heart failure. The flavonoid components of hawthorn may be responsible for hawthorn's beneficial effects in the treatment of heart failure. However, these components may also affect P-glycoprotein function and cause interactions with drugs that are P-glycoprotein substrates, such as digoxin, which is also used to treat heart failure. Therefore, the purpose of this study was to determine the effect of hawthorn on digoxin pharmacokinetic parameters. A randomized, crossover trial with 8 healthy volunteers was performed evaluating digoxin 0.25 mg alone (D) for 10 days and digoxin 0.25 mg with Crataegus special extract WS 1442 (hawthorn leaves with flowers; Dr. Willmar Schwabe Pharmaceuticals) 450 mg twice daily (D + H) for 21 days. Pharmacokinetic studies were performed for 72 hours. There were no statistically significant differences in any measured pharmacokinetic parameters. The AUC0-infinity, Cmax-Cmin, Cmin, and renal clearance for the D group were 79 +/- 26 mcg.h/L, 1.4 +/- 0.7 mcg/L, 0.84 +/- 0.2 mcg/L, and 74 +/- 10 mL/min versus 73 +/- 20 mcg.h/L, 1.1 +/- 0.1 mcg/L, 0.65 +/- 0.2 mcg/L, and 81 +/- 22 mL/min for the D + H group, respectively (p > 0.05). Following 3 weeks of concomitant therapy, hawthorn did not significantly alter the pharmacokinetic parameters for digoxin. This suggests that both hawthorn and digoxin, in the doses and dosage form studied, may be coadministered safely

J Herb Pharmcother. 2003;3(2):19-29. : Hawthorn evokes a potent anti-hyperglycemic capacity in streptozotocin-induced diabetic rats.
Jouad H, Lemhadri A, Maghrani M, Burcelin R, Eddouks M.
Errachida, Morocco,
m.eddouks@caramail.com

The hypoglycaemic effect of an aqueous extract of hawthorn leaves (Crataegus oxyacantha) was investigated in normal and streptozotocin (STZ) diabetic rats. After a single dose or 9 daily doses, oral administration of the aqueous extract produced a significant and dose-dependent decrease on blood glucose levels in STZ diabetic rats (P < 0.001), but had no effect on blood glucose levels in normal rats. No changes were observed in basal plasma insulin concentrations after treatment in normal or STZ diabetic rats. In addition, the acute toxicity study of the extract was investigated in mice. The results obtained showed that the aqueous extract had a high LD50 value (13.5 g/kg) in mice. We conclude that an aqueous extract of hawthorn leaves exhibits a potent anti-hyperglycemic activity in STZ rats, but not in normal rats, without affecting basal plasma insulin concentrations.

Planta Med. 2002 Jun;68(6):539-41. : Antiviral and antioxidant activity of flavonoids and proanthocyanidins from Crataegus sinaica.
Shahat AA, Cos P, De Bruyne T, Apers S, Hammouda FM, Ismail SI, Azzam S, Claeys M, Goovaerts E, Pieters L, Vanden Berghe D, Vlietinck AJ.

The antiviral and antioxidant activity of some fractions and of a series of flavonoids and proanthocyanidins obtained from Crataegus sinaica (Rosaceae) was evaluated. The O-glycosidic flavonoids and the oligomeric proanthocyanidins exhibited significant inhibitory activity against herpes simplex virus type 1 (HSV-1), which was shown to be due to an extracellular mechanism for procyanidin C-1. Procyanidin C-1 also had the highest antioxidant activity in both the microsomal lipid peroxidation and the hydroxyl radical scavenging assay. In addition to the previously reported phenolic compounds, the pentacyclic triterpenoid ursolic acid (1) and a tetrameric (2) and pentameric procyanidin (3) are reported for the first time.
Am J Health Syst Pharm. 2002 Mar 1;59(5):417-22.: Hawthorn: pharmacology and therapeutic uses.
Rigelsky JM, Sweet BV.
H. H. McGuire Veterans Affairs Medical Center, Richmond, VA, USA.

The uses, pharmacology, clinical efficacy, dosage and administration, adverse effects, and drug interactions of hawthorn are discussed. Hawthorn (Crataegus oxyacantha) is a fruit-bearing shrub with a long history as a medicinal substance. Uses have included the treatment of digestive ailments, dyspnea, kidney stones, and cardiovascular disorders. Today, hawthorn is used primarily for various cardiovascular conditions. The cardiovascular effects are believed to be the result of positive inotropic activity, ability to increase the integrity of the blood vessel wall and improve coronary blood flow, and positive effects on oxygen utilization. Flavonoids are postulated to account for these effects. Hawthorn has shown promise in the treatment of New York Heart Association (NYHA) functional class II congestive heart failure (CHF) in both uncontrolled and controlled clinical trials. There are also suggestions of a beneficial effect on blood lipids. Trials to establish an antiarrhythmic effect in humans have not been conducted. The recommended daily dose of hawthorn is 160-900 mg of a native water-ethanol extract of the leaves or flowers (equivalent to 30-169 mg of epicatechin or 3.5-19.8 mg of flavonoids) administered in two or three doses. At therapeutic dosages, hawthorn may cause a mild rash, headache, sweating, dizziness, palpitations, sleepiness, agitation, and gastrointestinal symptoms. Hawthorn may interact with vasodilating medications and may potentiate or inhibit the actions of drugs used for heart failure, hypertension, angina, and arrhythmias. The limited data about hawthorn suggest that it may be useful in the treatment of NYHA functional class II CHF.