Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Department of Physiology and Pathophysiology, Shaanxi Engineering and Research Center of Vaccine, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an 710061, China.
Institute of Pediatric Diseases, Xi'an Children's Hospital, Xi'an 710003, China.
Nutrients. 2023 Jan 18;15(3):502. doi: 10.3390/nu15030502.
Luteolin is widely distributed among a number of vegetal species worldwide. The pharmacological effects of luteolin are diverse and amongst antioxidant, free radical scavenging, and anti-inflammatory activities. Preliminary study showed that luteolin can ameliorate hypertension. However, the precise mechanism needs further investigation. There is no evidence that luteolin affects the paraventricular nucleus of the hypothalamus (PVN), a brain nucleus associated with a critical neural regulator of blood pressure. Our main aim was to explore the effect of luteolin on the PI3K/Akt/NF-κB signaling pathway within the PVN of hypertensive rats.
spontaneously hypertensive rats (SHRs) and corresponding normotensive control rats, the Wistar Kyoto (WKY) rats were divided into four groups and subsequently treated for 4 weeks with bilateral PVN injections of either luteolin (20 µg/0.11 µL, volume: 0.11 µL/h) or vehicle (artificial cerebrospinal fluid).
luteolin infusion to the PVN significantly decreased some hemodynamic parameters including the mean arterial pressure (MAP), heart rate (HR), circulating plasma norepinephrine (NE) and epinephrine (EPI). Additionally, there was a decrease in the expressions of the phosphatidylinositol 3-kinase (p-PI3K) and phosphorylated protein kinase-B (p-AKT), levels of reactive oxygen species (ROS), NAD(P)H oxidase subunit (NOX2, NOX4) in the PVN of SHRs. Meanwhile, the expression of inflammatory cytokines and the activity of nuclear factor κB (NF-κB) p65 in the PVN of SHRs were lowered. Furthermore, immunofluorescence results showed that injection of luteolin in the PVN reduced the expression of tyrosine hydroxylase (TH), and increased that of superoxide dismutase (SOD1) and the 67-kDa isoform of glutamate decarboxylase (GAD67) in the PVN of SHRs.
Our novel findings revealed that luteolin lowered hypertension via inhibiting NF-κB-mediated inflammation and PI3K/Akt signaling pathway in the PVN.
木犀草素广泛分布于世界各地的多种植物物种中。木犀草素的药理作用多种多样，具有抗氧化、自由基清除和抗炎活性。初步研究表明，木犀草素可以改善高血压。然而，确切的机制仍需进一步研究。目前尚无证据表明木犀草素有影响下丘脑室旁核（PVN）的作用，PVN 是与血压关键神经调节有关的脑核。我们的主要目的是探讨木犀草素对高血压大鼠 PVN 中 PI3K/Akt/NF-κB 信号通路的影响。
将自发性高血压大鼠（SHRs）和相应的正常血压对照大鼠 Wistar Kyoto（WKY）大鼠分为四组，随后用 PVN 双侧注射木犀草素（20µg/0.11µL，体积：0.11µL/h）或载体（人工脑脊液）治疗 4 周。
PVN 内注射木犀草素可显著降低一些血流动力学参数，包括平均动脉压（MAP）、心率（HR）、循环血浆去甲肾上腺素（NE）和肾上腺素（EPI）。此外，SHRs 的 PVN 中磷酸肌醇 3-激酶（p-PI3K）和磷酸化蛋白激酶 B（p-AKT）表达、活性氧（ROS）水平、烟酰胺腺嘌呤二核苷酸磷酸（NAD（P）H）氧化酶亚基（NOX2、NOX4）均降低。同时，SHRs 的 PVN 中炎症细胞因子的表达和核因子 κB（NF-κB）p65 的活性也降低。此外，免疫荧光结果显示，PVN 内注射木犀草素可降低酪氨酸羟化酶（TH）的表达，增加 SHRs 的 PVN 中超氧化物歧化酶 1（SOD1）和 67kDa 谷氨酸脱羧酶同工型（GAD67）的表达。
我们的新发现表明，木犀草素通过抑制 NF-κB 介导的炎症和 PVN 中的 PI3K/Akt 信号通路来降低高血压。
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