The Modulation of Arachidonic Acid Metabolism and Blood Pressure-Lowering Effect of Honokiol in Spontaneously Hypertensive Rats

Abstract

Background: Cardiovascular diseases have consistently been the leading cause of death in the United States over the last two decades, with 30% of the adult American population having hypertension. The metabolites of arachidonic acid (AA) in the kidney play an important role in blood pressure regulation. The present study investigates the antihypertensive effect of honokiol (HON), a naturally occurring polyphenol, and examines its correlation to the modulation of AA metabolism. Methods: Spontaneously hypertensive rats (SHR) were randomly divided into four groups. Treatment groups were administered HON intraperitoneally at concentrations of 5, 20, and 50 mg/kg. Blood pressure was monitored at seven-day intervals. After a total of 3 weeks of treatment, the rats were euthanized and the kidney tissues were collected to examine the activity of the two major enzymes involved in AA metabolism in the kidney, namely cytochrome P450 (CYP)4A and soluble epoxide hydrolase (sEH). Results: Rats treated with HON did not experience the rise in blood pressure observed in the untreated SHR. High-dose HON significantly reduced blood pressure and inhibited the activity and protein expression of the CYP4A enzyme in the rat kidney. The activity of the sEH enzyme in renal cytosol was significantly inhibited by medium and high doses of HON. Conclusion: Our data demonstrate the antihypertensive effect of HON and provide a novel mechanism for its underlying cardioprotective properties.

Catechin Reduces Blood Pressure in Spontaneously Hypertensive Rats through Modulation of Arachidonic Acid Metabolism

“…Recently, the inhibition of sEH and increased bioavailability of EETs have been proposed as promising approaches for the prevention and treatment of hypertension. Our research and others have shown that the sub-chronic inhibition of sEH for 1–6 weeks lowers blood pressure and ameliorates the organ damage associated with hypertension [ 7 , 10 , 11 , 12 ].…”

“…Our laboratory has been interested in the past two decades in understanding the health benefits of small natural molecules [ 7 , 12 , 13 , 16 , 19 , 20 ]. Catechin (CAT) is among the most abundant and commonly studied flavonoid that exists in a wide variety of foods and herbs.…”

“…Therefore, the inhibition of sEH and enhancing the bioavailability of EETs have been suggested as a relevant therapeutic strategy for the prevention of hypertension and protecting the kidney from hypertension-induced damage [ 11 , 17 ]. Earlier studies have demonstrated that the acute and chronic inhibition of sEH activity increases EET levels, lowers arterial blood pressure, and perfects against end-organ damage associated with renal and cardiovascular diseases [ 7 , 12 , 14 , 20 ]. The current study indicates that the high dose of CAT reduces the renal activity of sEH by 40% ( Figure 5 ), and this inhibition was significantly correlated to lowering MAP ( Figure 6 ).…”

“…The kidneys were rapidly removed, rinsed with ice-cold saline, and snap-frozen in liquid nitrogen, then stored at −80 °C until use. Kidney microsomal and cytosolic fractions were prepared from the renal cortex using an ultracentrifugation protocol as described previously [ 12 ].…”

“…Investigating the effect of naturally occurring phytochemicals on the renal metabolism of AA and their potential to reduce blood pressure has been the focus of our laboratory in the last decade. Our research has identified the blood pressure-lowering effects of several small natural products through the modulation of one or more of the AA metabolic pathways in the kidney [ 7 , 12 , 13 ]. Catechin (CAT), in Figure 1 , is a natural flavonoid that is abundant in plant-based foods, especially cocoa.…”