Animal Studies

Studies with isolated perfused rat heart indicate a cardioprotective effect of hawthorn extracts on the ischemic-reperfused heart and this effect is not accompanied by the increase in coronary flow (31). This protection may be coupled to the antioxidative properties of hawthorn extract, which inhibits formation of free radicals (32,33) and subsequent injury to the heart. A significant reduction in the time spent on ventricular fibrillation was observed by infusion of an extract from flowering tops of Crataegus meyei A. Pojark. In anesthetized rats, a bolus injection of the extract lowered blood pressure (34). These effects indicate that the extract of C. meyei may have a hypotensive and an antiarrthymic action on ischemic myocardium.

Cardioprotective effects of WS 1442 may be partly attributable to the strong free-radical-scavenging activity of some bioactive constituents such as flavonoids and oligomeric procyanidins. Oral administration of WS 1442 at a dose of 100 mg/kg/day to rats shows a significant protection against ischemia-reperfusion-induced pathologies (35).

C. In Vitro Studies

Even though both human and animal studies show the hypotensive effect of hawthorn extract, the underlying cellular mechanisms are completely unclear. It is possible that hawthorn extract may target both endothelium and vascular smooth muscle cells to cause vasodilation. We have recently demonstrated that hawthorn extract produces dose-dependent relaxation mainly in an endothelium-dependent manner in isolated rat mesenteric arteries. Figure 6

Fraction 6000-8000 (mg/mL) Fraction 12,000-14,000 (mg/mL)

Figure 6 The cumulative dose-response curves for the relaxant response to an extract from a hawthorn drink following dialysis in both endothelium-intact (O) and -denuded (•) rings prepared from rat mesenteric arteries. The rings were preconstricted by 50 nM U46619. Data are means ± SEM of six experiments. The molecular weight cutoffs of the dialysis membranes to remove small molecules are as indicated. The active material appears to be retained between 3500 and 8000 molecular weight cutoff.

Fraction 6000-8000 (mg/mL) Fraction 12,000-14,000 (mg/mL)

Figure 6 The cumulative dose-response curves for the relaxant response to an extract from a hawthorn drink following dialysis in both endothelium-intact (O) and -denuded (•) rings prepared from rat mesenteric arteries. The rings were preconstricted by 50 nM U46619. Data are means ± SEM of six experiments. The molecular weight cutoffs of the dialysis membranes to remove small molecules are as indicated. The active material appears to be retained between 3500 and 8000 molecular weight cutoff.

shows that in U46619-preconstracted rat mesenteric artery rings, hawthorn extract from a fruit drink (the same one we used to perform the clinical trial in Section II) induces primarily endothelium-dependent relaxation after removal of small molecules via dialysis with membranes of molecular weight cutoff at 3500, 6000-8000, and 12,000-14,000 kDa.

Removal of the functional endothelium abolishes the relaxant effect of hawthorn extract. The hawthorn-extract-induced relaxation can be readily washed out and is highly repeatable. The relaxant effect of hawthorn extract is concentration-dependently attenuated by pretreatment of rat mesenteric arteries with an inhibitor of nitric oxide synthase, NG-nitro-L-arginine methyl ester, or an inhibitor of gunaylate cyclase, methylene blue, while L-arginine, the nitric oxide precursor, partly antagonizes the effect of NG-nitro-L-arginine methyl ester (36). In addition to nitric oxide, the endothelium also releases prostacyclin or endothelium-derived hyperpolarizing factor in response to various stimuli. However, indomethacin (an inhibitor of cyclooxygenase that catalyzes biosynthesis of prostacyclin), glibenclamide (a blocker of vascular ATP-sensitive potassium channels), or iberiotoxin (a blocker of calcium-activated potassium channel) did not influence the vasorelaxant response to hawthorn extract, suggesting that the relaxing prostanoids or calcium-activated or ATP-sensitive potassium channels are not involved. Hawthorn extract produces significantly less relaxant effect in endothelium-intact artery rings preconstricted by 60 mM extracellular potassium. In endothelium-denuded rings contracted by elevated potassium, hawthorn extract was still able to induce relaxation albeit to much lesser degree. Raising extracellular potassium would bring the membrane potential nearer to the new equilibrium potential for potassium efflux; thus the effect of potassium channel activation on transmembrane calcium movement should be minimized. Reduced effect on high potassium-induced contraction indicates that hawthorn extract may also stimulate release of some unknown endothelium-derived factors that could hyperpolarize the cell membrane of the underlying vascular smooth muscle via opening of potassium channels. The endothelial nitric-oxide-mediated relaxation is supported by the ability of hawthorn extract to raise the tissue content of cyclic GMP in endothelium-intact rat aortas. This effect can be abolished by endothelium denuation or by inhibitors of nitric-oxide-mediated relaxation, such as NG-nitro-L-arginine (personal communication).

Endothelial nitric oxide seems to play a differential role in hawthorn-extract-induced relaxation in the rat arteries prepared from different vascular beds. For example, hawthorn extract only produces endothelium-indepen-dent relaxation in isolated rat cerebral, carotid, and coronary arteries (37) since neither endothelial removal nor nitric oxide synthase inhibitors had an effect. It is currently unknown what has caused this discrepancy in the vascular response to hawthorn extract in different arteries. It is suggested that some bioactive components in hawthorn extract may have a direct muscle relaxant action, e.g., possible inhibition of calcium influx in arterial smooth muscle cells (38).

One recent study described that procyanidins in hawthorn extract (Crataegus oxyacantha, L.) may be responsible for the endothelium/nitric-oxide-dependent relaxation in rat aortas, probably through activation of tetraethylammonium-sensitive potassium channels (38). However, our results indicate other unknown ingredients may be involved since procyanidins were undetectable in the dialyzed hawthorn extract sample on HPLC. Monoacetyl-vitexinrhamnoside, a flavonoid with phosphodiesterase-inhibitory property contained in another Crataegus species (hawthorn, Rosaceas), was also found to induced relaxation in rabbit isolated femoral arteries and this relaxation was inhibited by NG-nitro-L-arginine (39). In Langendorff- rabbit hearts, monoacetyl-vitexinrhamnoside enhanced heart rate, cardiac contractility, and coronary flow (39), suggesting that this flavonoid has an anti-ischemic effect probably through improvement of myocardial perfusion.

In addition to antioxidant and hypocholesterolemic activity of hawthorn extract, the vasorelaxant effect on various blood vessels suggests the potential preventive action of this plant against cerebral or coronary circulation-associated disease such as cerebral vasospasm and coronary artery disease. The endothelium/nitric-oxide-dependent action indicates that hawthorn fruit extract may have a wide spectrum of benefits in the cardiovascular system.

Relaxation Audio Sounds Lazy Summer Day

Relaxation Audio Sounds Lazy Summer Day

This is an audio all about guiding you to relaxation. This is a Relaxation Audio Sounds with sounds from Lazy Summer Day.

Get My Free MP3 Audio


Post a comment