School of Pharmacy, Pacific University, Hillsboro, OR 97123, USA.
Molecules. 2022 May 25;27(11):3396. doi: 10.3390/molecules27113396.
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.
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).
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.
Our data demonstrate the antihypertensive effect of HON and provide a novel mechanism for its underlying cardioprotective properties.
在过去的二十年中，心血管疾病一直是美国的主要死因，有 30%的美国成年人患有高血压。肾脏中花生四烯酸（AA）的代谢物在血压调节中起着重要作用。本研究探讨了厚朴酚（HON）的降压作用，HON 是一种天然存在的多酚，并研究了其与 AA 代谢调节的相关性。
自发性高血压大鼠（SHR）随机分为四组。治疗组腹腔内给予 HON 浓度为 5、20 和 50mg/kg。每隔七天监测血压。经过 3 周的治疗后，处死大鼠并收集肾脏组织，以检测肾脏中参与 AA 代谢的两种主要酶的活性，即细胞色素 P450（CYP）4A 和可溶性环氧化物水解酶（sEH）。
用 HON 治疗的大鼠未出现未治疗 SHR 中观察到的血压升高。高剂量 HON 可显著降低血压，并抑制大鼠肾脏中 CYP4A 酶的活性和蛋白表达。中、高剂量 HON 可显著抑制肾胞质中 sEH 酶的活性。
我们的数据表明 HON 具有降压作用，并为其潜在的心脏保护特性提供了新的机制。
