br Materials and methods br Results
Materials and methods
Discussion The result of phytochemical screening revealed the overwhelming presence of flavonoids in the ethylacetate extract of A. cepa tunic (ACTE). The finding is in agreement with previous works [22,23] which showed that ethylacetate fractions contain high amount of phenolics/flavoniods, thus initiating their uses as flavonoid-rich sources. Flavonoids have aroused considerable interest recently because of their potential beneficial effects on human health. In line with previous findings on onions [5,24], HPLC screening of flavonoids in ACTE revealed the flavonols: kaempferol, quercetin and quercetin glycosides (isoquercitrin, quercitrin and rutin) as the active flavonoids. In the present study, we observed marked decreases in the systolic and diastolic pressure, mean arterial blood pressure, pulse rate and ionophores rate of rats administered ACTE. The hypotensive effect of ACTE could be of therapeutic benefit in the event of clinical or drug-induced elevated blood pressure or hypertension  where reduction in blood pressure is highly desirable. The result was comparable to that recorded for the popular angiotensin-converting enzyme (ACE) inhibitor and hypotensive drug, ramipril. It might be impossible to categorically ascertain the mechanism underlying the hypotensive effect of ACTE from the data obtained in this study. It is however known that ACE inhibitors such as ramipril and catopril lower blood pressure and bring about fewer cardiovascular events in high risk populations by binding a zinc molecule at the active site of ACE, thereby slowing down the conversion of angiotensin I to the potent vasoconstrictor, angiotensin II . Quercetin and its glycosides are often the most abundant polyphenolic compounds found in the human diet, and richly found in the peel of onions [4,5,24]. Several beneficial cardiovascular effects have been ascribed to this phytochemical, including antihypertensive effect and ability to improve endothelial function [27,28]. Flavonoids are known to bind metal ions, such as zinc, and there is evidence that quercetin may inhibit ACE activity via this mechanism . Olaleye et al.  reported that rutin and quercetin reduced the blood pressure of animals induced with high salt diet. Overstimulation of the renin-angiotensin system (RAS), and by extension ACE, is one means by which high salt concentration induces hypertension . Going by the aforementioned, it is safe to hypothesize that ACTE could exert its hypotensive effect by interfering with ACE through one or more of its constituent flavonoids. In the present study, ACTE did not adversely affect serum total cholesterol and markers of tissue injury: creatine kinase CK, aspartate aminotransferase AST and alanine aminotransferase ALT. Serum CK and AST have been used as indicators of the stage of myocardial injury . The activities of these cellular enzymes present in the blood are directly related to the intactness of the plasma membrane of the cardiac cells. Therefore, the inhibition of the release of these enzymes into the serum by ACTE could be due to the ability of some of the flavonoids present in the extract to maintain cardiac membrane integrity and restrict the leakage of these enzymes . Conversely, the ability of the ACTE to reduce serum cholesterol in treated animals portrays good signal for cardioprotection taken into consideration the role hyperlipidemia plays in the etiology and progression of many cardiovascular diseases [33,34]. Superoxide dismutase (SOD) and catalase are endogenous antioxidant enzymes responsible for the dismutation of superoxide radicals to H2O2 and detoxification of H2O2 to water, respectively. Coupled with the actions of the master endogenous antioxidant molecule, GSH, these enzymes offer protection against tissue damage . In the present study, we observed an increase in the activities of cardiac SOD and catalase with concomitant decrease in GSH. The observed effect on GSH is a deviation from the well-established antioxidant activity of flavonoids . It is however known that in vivo, some flavonoid metabolites exhibit prooxidative tendencies , some of which proceed via concentration-dependent stimulation of H2O2 production [35,38]. Such prooxidative tendency does not necessarily indicate toxicity in its entirety but could be beneficial and capable of causing overall cytoprotection , since levels of some antioxidant defenses and biotransformation enzymes might be elevated due to the mild degree of oxidative stress ensuing . Oxidative metabolites of flavonoid such as quercetin are preferably inactivated by the major intracellular reducing agent GSH, to form two non-reactive products . The reduced level of GSH could thus be due to the modulation of several biological processes by flavonoids .