Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
Food Funct. 2020 Feb 26;11(2):1322-1333. doi: 10.1039/c9fo02365h.
Tangeretin is a citrus flavonoid that exerts several beneficial effects, including anti-inflammation, anti-oxidation and neuroprotection. In this study, the aim was to test the effect of tangeretin on Nω-Nitro-l-arginine methyl ester (l-NAME)-induced high blood pressure, and left ventricular dysfunction and remodeling in rats. Rats were divided into five groups (n = 8 per each group): a control group, an l-NAME group and three l-NAME groups treated with tangeretin (15 mg kg-1) or tangeretin (30 mg kg-1) or captopril (5 mg kg-1) for the final two weeks. After five weeks of experiment, l-NAME groups had high systolic blood pressures, and ventricular dysfunction and remodeling. Overexpression of angiotensin II type 1 receptor, phosphorylated-extracellular-regulated kinase 1/2 (pERK1/2), and phosphorylated-c-Jun N-terminal kinase (pJNK) protein but downregulation of endothelial nitric oxide synthase (eNOS) protein expression in ventricular tissues were observed in hypertensive rats while the protein expression of phosphorylated-mitogen activated protein kinase p38 did not differ among groups. The decrease in plasma NOx and increase in vascular superoxide generation, plasma malondialdehyde, angiotensin-converting enzyme activity and angiotensin II levels were found in hypertensive rats. These alterations were suppressed in hypertensive rats treated with tangeretin or captopril. In conclusion, tangeretin exhibits antihypertensive effects and alleviates ventricular dysfunction and remodeling in hypertensive rats. These effects are associated with the inhibition of renin angiotensin system activation and restoration of pERK1/2, pJNK, and eNOS protein expressions along with reduced oxidative stress and increased NO bioavailability.
蜜橘素是一种柑橘类黄酮，具有多种有益作用，包括抗炎、抗氧化和神经保护。本研究旨在检测蜜橘素对 Nω-硝基-L-精氨酸甲酯（l-NAME）诱导的高血压以及大鼠左心室功能障碍和重构的影响。大鼠分为五组（每组 n = 8）：对照组、l-NAME 组和三个 l-NAME 组，分别用蜜橘素（15 mg/kg）或蜜橘素（30 mg/kg）或卡托普利（5 mg/kg）治疗最后两周。实验五周后，l-NAME 组大鼠收缩压升高，出现心室功能障碍和重构。高血压大鼠心室组织中血管紧张素 II 型 1 受体、磷酸化细胞外调节激酶 1/2（pERK1/2）和磷酸化 c-Jun N-末端激酶（pJNK）蛋白表达过度，内皮型一氧化氮合酶（eNOS）蛋白表达下调，但磷酸化丝裂原激活蛋白激酶 p38 蛋白表达在各组之间无差异。高血压大鼠血浆 NOx 降低，血管超氧化物生成、血浆丙二醛、血管紧张素转换酶活性和血管紧张素 II 水平增加。这些变化在给予蜜橘素或卡托普利治疗的高血压大鼠中受到抑制。综上所述，蜜橘素具有降压作用，并减轻高血压大鼠的心室功能障碍和重构。这些作用与抑制肾素-血管紧张素系统激活以及恢复 pERK1/2、pJNK 和 eNOS 蛋白表达有关，同时还降低了氧化应激，增加了 NO 的生物利用度。
