Centre of Experimental Medicine, Slovak Academy of Sciences, Institute of Normal and Pathological Physiology, Sienkiewiczova 1, 813 71 Bratislava, Slovakia.
Faculty of Medicine, Institute of Pharmacology and Clinical Pharmacology, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia.
Int J Mol Sci. 2023 Aug 9;24(16):12616. doi: 10.3390/ijms241612616.
The effect of a 10-day-long treatment with taxifolin (TAX, 20 mg/kg/day p.o.) was investigated on spontaneously hypertensive rats (SHRs) with a focus on the vascular functions of isolated femoral arteries and thoracic aortas. TAX reduced blood pressure in SHRs. In femoral arteries, TAX increased acetylcholine-induced relaxation, reduced the maximal NA-induced contraction, and reduced acetylcholine-induced endothelium-dependent contraction (EDC); however, TAX had no effect on the vascular reactivity of isolated thoracic aortas. In addition, TAX elevated the total nitric oxide synthase (NOS) activity and iNOS protein expression but reduced cyclooxygenase-2 (COX2) protein expression in the tissue of the abdominal aorta without changes in and gene expressions. TAX also increased the gene expression of the anti-inflammatory interleukin-10 (). In addition, in vitro studies showed that TAX has both electron donor and H atom donor properties. However, TAX failed to reduce superoxide production in the tissue of the abdominal aorta after oral administration. In conclusion, our results show that a decrease in the blood pressure in TAX-treated SHRs might be attributed to improved endothelium-dependent relaxation and reduced endothelium-dependent contraction. In addition, the results suggest that the effect of TAX on blood pressure regulation also involves the attenuation of COX2-mediated pro-inflammation and elevation of anti-inflammatory pathways.
为期 10 天的杉黄酮(TAX,每天 20 毫克/千克口服)治疗对自发性高血压大鼠(SHR)的影响,重点是研究其对分离的股动脉和胸主动脉的血管功能的影响。TAX 降低了 SHR 的血压。在股动脉中,TAX 增加了乙酰胆碱诱导的松弛作用,降低了最大去甲肾上腺素诱导的收缩作用,降低了乙酰胆碱诱导的内皮依赖性收缩(EDC);然而,TAX 对分离的胸主动脉的血管反应没有影响。此外,TAX 增加了腹主动脉组织中总一氧化氮合酶(NOS)活性和诱导型 NOS 蛋白表达,但降低了环氧化酶-2(COX2)蛋白表达,而 和 基因表达没有变化。TAX 还增加了抗炎白细胞介素-10()的基因表达。此外,体外研究表明,TAX 具有电子供体和 H 原子供体的性质。然而,TAX 经口服给药后未能减少腹主动脉组织中超氧化物的产生。总之,我们的结果表明,TAX 治疗的 SHR 血压降低可能归因于改善的内皮依赖性松弛和降低的内皮依赖性收缩。此外,结果表明,TAX 对血压调节的影响还涉及 COX2 介导的促炎作用的减弱和抗炎途径的升高。