Flavonoids hawthorn

Rayyan, S. et al.. Isolation and identification of flavonoids including fiavone rotamers from the herbal drug Crataegi folium cum flore, hawthorn, Phytochem. Anal., 2004, in press. 

In addition to the induction of anthocyanin biosynthesis, chilling stress has also been shown to promote the formation of colorless flavonoids. Cold treatments (and drought stress) caused increases in levels of (—)-epicatechin and hyperoside (quercetin 3-galactoside) in two species of hawthorn, Crataegus laevigata and C. monogyna. Such treatments also enhanced the antioxidant capacity of the shoot extracts, and this may be the primary function of these cold-inducible flavonoids. 

It is a diuretic. An extract of the flowers and leaves improves cardiac output and the contractility of the heart muscle. Flavonoids in hawthorn have been shown to increase blood flow in the heart by dilating blood vessels in coronary arteries. Hawthorn has lowered cholesterol in animal studies, probably due to its oligomeric procyanidins (OPC), a type of bioflavonoid similar to that found in the extracts of grape seed and grape skin. 

Svedstrom, U. Vuorela, H. Kostiainen, R. Laakso, L Hiltunen, R. 2006. Fractionation of polyphenols in hawthorn into polymeric procyanidins, phenolic acid, and flavonoids prior to high-performance liquid chromatographic analysis. J. Chromatogr. A. 1112 103-111. 

Crataegus species (hawthorn, maybush, whitethorn) contain a variety of flavonoids, including rhamnosides, schaf-tosides, and spiraeosides. They have a positive inotropic effect on the heart by a mechanism different from that of cardiac glycosides, catecholamines, and the phosphodiesterase type III inhibitors (1) and are effective in mild heart failure (2). 

The flavonoids present in hawthorn purportedly have a sedative effect (2,5). 

Drug interactions with hawthorn are theoretically possible with cardioactive medications, but have not been documented (2). In addition, the flavonoid constituents have been shown to have inhibitory and inducible effects on the cytochrome P-450 enzyme system, making other drug interactions possible (20). However, an in vivo study of a potential pharmacokinetic interaction of digoxin and hawthorn demonstrated that concurrent administration had no effect on digoxin pharmacokinetics, suggesting that the two could be safely administered together from a pharmacokinetic point of view (21). However, one must be mindful of additive effects and a potential pharmacodynamic interaction. 

HAWTHORN, Cmtaesi folium cum /lore, fructus. A draft monograph on Hawthorn leaf with flower has been published by the European Pharmacopoeia which defines the drug as the dried whole or cut flower-bearing branches, up to 7 cm long, of Cmtae [us mon iyna Jac., Cmtae ius laevi iata, (Poir.) D.C. (C. oxyacantha, L.) or their hybrids or more rarely other Cmtae ius species. Hawthorn contains not less than 1.5% of flavonoids calculated as hyperoside. 

Hawthorn extracts purportedly dilate coronary blood vessels, decrease blood pressure, increase myocardial contractility, and lower serum cholesterol (Anonymous, 1999). Benefits have been demonstrated in heart failure patients (Iwamoto et al., 1981). In patients with Stage II New York Heart Association (NYHA) heart failure, doses of 160-900 mg/d of the aqueous-alcoholic extract for up to 56 d showed an increase in exercise tolerance, decrease in rate/pressure product, and increased ejection fraction (Blumenthal, 1998). The active principles are thought to be flavonoids, including hyperoside, vitexin, vitexin-rhamnose, rutin, and oligomeric procyanidins (dehydrocatechins catechins and/or epicatechins) (Tyler, 1993 Blumenthal, 1997 Blumenthal, 1998 Bigus, 1998). 

Bahorun and colleagues describe the use of thin-layer chromatography (TLC) to determine total proanthocynidins, phenol, and flavonoid content of hawthorn extracts. High-performance liquid chromatography (HPLC) analysis using a UV detector at 280 nm for proanthocyanidins and phenolic acids, and 360 nm for flavonoids is also described (Bahorun et al., 1996). 

Kappenberg [68] derivatized sample solutions of inflorescenses of hawthorn and lime (Tilia sp.), among other species, with dansylchloride (5-dimethylamino-l-naphthalinsulfonyl chloride) prior to thin layer chromatography on silica. Detection is based on the measurement of fluorescence at 365 nm. Under the applied experimental conditions phenolic acids and flavonoid glycosides remained at the start, whereas derivatives of B-type procyanidin dimers were developed as a single spot. The sensitivity was reported to be ten times higher compared to the vanillin condensation products. Drawbacks of this method are that it is sensitive to light and that so far, no studies on reaction kinetics of individual procyanidins have been performed. 

Water stress may upregulate the phenyl propanoid synthesis pathway and hence enhance the level of anthocyanin and hydroxycinnamic acids contributing to elevated levels of antioxidants in sweet potato roots (Philpott et al. 2003). Drought and cold stresses elevated (-)-epicatechin and some flavonoid levels in hawthorn... 

No adverse effects were observed in offspring of mice fed a flavonoid mixture obtained from the leaf of hawthorn at a dose of 100 mg/kg daily for 1 month (Manolov and Daleva 1969). No teratogenic effects were observed in pregnant rats and rabbits orally administered 1.6 g/kg of a hydroethanolic extract of hawthorn leaf and flower. The same study showed no postnatal toxicity in rats or their offspring (ESCOP 2003). 

It is instructive to concentrate on the flavonoids, as these are of primary importance in qualitative assays of several HDs. Silica gel as stationary phase and ethyl acetate-ethyl methyl ketone-formic acid-water (50 30 10 10 by volume) as mobile phase is used in the analysis of flavonoids with C-glycosides (hawthorn, passion flower), and a mobile phase of ethyl acetate-formic acid-acetic acid-water (100 11 11 27 by volume) is used as the basic solvent for 0-glycosides (arnica, calendula, chamomille). Following spraying of the plates with 2-aminoethyldiphenyl-borinate (NTS, 1% in methanol) and subsequent treatment with poly(ethylene glycol) 4000 (PEG, 5% in ethanol), flavonoids display yellow to green fluorescence under UV irradiation at 365 nm. The frequently observed blue spots represent phenol... 

Wu C, Zhang J, Zhou T, Guo B, Wang Y, Hou J (2011) Simultaneous determination of seven flavonoids in dog plasma by ultra-performance liquid chromatography-tandem mass spectrometry and its application to a bioequivalence study of bioactive components in Herba epimedii and Er-Xian Decoction. J Pharm Biomed Anal 54 186-191 Ma G, Jiang X-H, Chen Z, Ren J, Li C-R, Liu T-M (2007) Simultaneous determination of vitexin-4"-0-glucoside and vitexin-2 -0-rhamnoside from hawthorn leaves flavonoids in rat plasma by HPLC method and its application to pharmacokinetic studies. J Pharm Biomed Anal 44 243-249... 

Compounds associated with cardiotonic activity include hyperoside, vitexin, vitexin-2 -rhamnoside, oligomeric procyanidins, and (—)-epicatechin. Tbe flavonoids and oligomeric procyanidins have a tonic effect on tbe cardiac muscles, are negatively cbronotropic and dromotropic, and also show tbe bradycar-diac effect commonly noted for Crataegus (list and horhammer)/ Flavonoids may also be the major constituents responsible for the hypolipidemic effect of hawthorn by regulating lipoprotein lipases expression. ... 

Polyphenolic compounds are determined mainly in the plasma, rather than in whole blood and in urine. The research, in the majority of cases, relate to samples from patients who take dietary supplements containing polyphenols or are on a diet rich in such compounds. Biological fluid samples are collected at different time intervals after the administration of the herbal preparation (e.g., Hippophae rhamnoides (20), Hawthorn leaves flavonoids (21), GegenQinlian decoction (22), Flos Lonicerae japonicae (23)) containing different amounts of polyphenols. The isolation and preconcentration of analytes of these samples usually precedes the enzymatic hydrolysis (24—28) or acid hydrolysis (20), which is based on the conversion of glucuronide and sulfate derivatives of polyphenolic compounds formed in phase II metabolism to the basic forms of polyphenols. To carry out the enzymatic hydrolysis there are... 

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