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Apigenin Improves Hypertension and Cardiac Hypertrophy Through Modulating NADPH Oxidase-Dependent ROS Generation and Cytokines in Hypothalamic Paraventricular Nucleus
Cardiovascular Toxicology ( IF 3.2 ) Pub Date : 2021-06-02 , DOI: 10.1007/s12012-021-09662-1
Hong-Li Gao 1 , Xiao-Jing Yu 1 , Han-Bo Hu 1 , Qian-Wen Yang 1 , Kai-Li Liu 1 , Yan-Mei Chen 1 , Yan Zhang 1 , Dong-Dong Zhang 1 , Hua Tian 1 , Guo-Qing Zhu 2 , Jie Qi 1 , Yu-Ming Kang 1
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Apigenin, identified as 4′, 5, 7-trihydroxyflavone, is a natural flavonoid compound that has many interesting pharmacological activities and nutraceutical potential including anti-inflammatory and antioxidant functions. Chronic, low-grade inflammation and oxidative stress are involved in both the initiation and progression of hypertension and hypertension-induced cardiac hypertrophy. However, whether or not apigenin improves hypertension and cardiac hypertrophy through modulating NADPH oxidase-dependent reactive oxygen species (ROS) generation and inflammation in hypothalamic paraventricular nucleus (PVN) has not been reported. This study aimed to investigate the effects of apigenin on hypertension in spontaneously hypertensive rats (SHRs) and its possible central mechanism of action. SHRs and Wistar-Kyoto (WKY) rats were randomly assigned and treated with bilateral PVN infusion of apigenin or vehicle (artificial cerebrospinal fluid) via osmotic minipumps (20 μg/h) for 4 weeks. The results showed that after PVN infusion of apigenin, the mean arterial pressure (MAP), heart rate, plasma norepinephrine (NE), Beta 1 receptor in kidneys, level of phosphorylation of PKA in the ventricular tissue and cardiac hypertrophy, perivascular fibrosis, heart level of oxidative stress, PVN levels of oxidative stress, interleukin 1β (IL-1β), interleukin 6 (IL-6), iNOS, monocyte chemotactic protein 1 (MCP-1), tyrosine hydroxylase (TH), NOX2 and NOX4 were attenuated and PVN levels of interleukin 10 (IL-10), superoxide dismutase 1 (Cu/Zn-SOD) and the 67-kDa isoform of glutamate decarboxylase (GAD67) were increased. These results revealed that apigenin improves hypertension and cardiac hypertrophy in SHRs which are associated with the down-regulation of NADPH oxidase-dependent ROS generation and inflammation in the PVN.



中文翻译:

芹菜素通过调节下丘脑室旁核中 NADPH 氧化酶依赖性 ROS 的产生和细胞因子来改善高血压和心脏肥大

芹菜素,被鉴定为 4', 5, 7-trihydroxyflavone,是一种天然类黄酮化合物,具有许多有趣的药理活性和营养潜力,包括抗炎和抗氧化功能。慢性、低度炎症和氧化应激与高血压和高血压引起的心脏肥大的发生和进展有关。然而,芹菜素是否通过调节 NADPH 氧化酶依赖性活性氧 (ROS) 生成和下丘脑室旁核 (PVN) 炎症来改善高血压和心脏肥大尚未见报道。本研究旨在探讨芹菜素对自发性高血压大鼠 (SHR) 高血压的影响及其可能的中心作用机制。SHR 和 Wistar-Kyoto (WKY) 大鼠被随机分配,并通过渗透性微型泵 (20 μg/h) 用双侧 PVN 输注芹菜素或载体(人工脑脊液)治疗 4 周。结果显示,在PVN输注芹菜素后,平均动脉压(MAP)、心率、血浆去甲肾上腺素(NE)、肾脏中的β1受体、心室组织中PKA的磷酸化水平和心脏肥大、血管周围纤维化、心脏氧化应激水平、PVN 氧化应激水平、白细胞介素 1β (IL-1β)、白细胞介素 6 (IL-6)、iNOS、单核细胞趋化蛋白 1 (MCP-1)、酪氨酸羟化酶 (TH)、NOX2 和 NOX4 均减弱白细胞介素 10 (IL-10)、超氧化物歧化酶 1 (Cu/Zn-SOD) 和谷氨酸脱羧酶 (GAD67) 的 67-kDa 同种型的 PVN 和 PVN 水平增加。

更新日期:2021-06-02
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