Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
Faculty of Veterinary Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
Eur J Pharmacol. 2023 Dec 5;960:176112. doi: 10.1016/j.ejphar.2023.176112. Epub 2023 Oct 23.
Kaempferol is a natural flavonoid compound that exhibits various pharmacological actions. However, there are few reports regarding the role of kaempferol in cardiovascular abnormalities. This study aimed to assess whether kaempferol could prevent cardiovascular malfunction and hypertrophy provoked by chronic inhibition of nitric oxide (NO) formation in rats. Rats (180-200 g) were treated daily with N-nitro-L-arginine methyl ester hydrochloride (L-NAME) (40 mg/kg, in drinking water) for five weeks concomitant with kaempferol (oral administration) at a dose of 20 mg/kg or 40 mg/kg or lisinopril (5 mg/kg). Kaempferol partially prevented the progression of hypertension provoked by NO inhibition (p < 0.05). Left ventricular malfunction and hypertrophy present in hypertensive rats were alleviated by concurrent administration of kaempferol (p < 0.05). Furthermore, L-NAME rats had increased sympathetic nerve-mediated vasoconstriction and decreased acetylcholine-induced vasorelaxation and aortic wall thickening, which were resolved by kaempferol treatment (p < 0.05). Kaempferol restored tissue superoxide formation, malondialdehyde, catalase activity, plasma nitric oxide metabolites, tumor necrosis factor-alpha (TNF-α) and interleukin-6 in L-NAME rats (p < 0.05). Overexpression of tumor necrosis factor receptor 2 (TNFR2), phosphatidylinositol 3-kinases (PI3K), AKT serine/threonine kinase 1 (Akt1) and smad2/3 in heart tissue and upregulation of tumor necrosis factor receptor 1 (TNFR1), phosphorylated nuclear factor-kappaB (p-NF-κB) and transforming growth factor beta 1 (TGF-β1) in vascular tissue were suppressed by kaempferol (p < 0.05). In conclusion, kaempferol exerts antihypertensive, cardioprotective, antioxidant, and anti-inflammatory effects in NO-dependent hypertensive rats. The underlying mechanisms of kaempferol in preventing cardiovascular changes induced by L-NAME were due to the suppression of the TNF-α pathway.
山奈酚是一种天然类黄酮化合物，具有多种药理作用。然而，关于山奈酚在心血管异常中的作用的报道很少。本研究旨在评估山奈酚是否可以预防慢性抑制一氧化氮（NO）形成引起的大鼠心血管功能障碍和肥大。大鼠（180-200g）每天用 N-硝基-L-精氨酸甲酯盐酸盐（L-NAME）（40mg/kg，在饮用水中）处理五周，同时给予山奈酚（口服）剂量为 20mg/kg 或 40mg/kg 或赖诺普利（5mg/kg）。山奈酚部分预防了由 NO 抑制引起的高血压的进展（p<0.05）。高血压大鼠左心室功能障碍和肥大通过同时给予山奈酚得到缓解（p<0.05）。此外，L-NAME 大鼠的交感神经介导的血管收缩增加，乙酰胆碱诱导的血管舒张和主动脉壁增厚减少，这些变化通过山奈酚治疗得到解决（p<0.05）。山奈酚恢复了组织中超氧化物形成、丙二醛、过氧化氢酶活性、血浆一氧化氮代谢物、肿瘤坏死因子-α（TNF-α）和白细胞介素-6 在 L-NAME 大鼠中的水平（p<0.05）。肿瘤坏死因子受体 2（TNFR2）、磷脂酰肌醇 3-激酶（PI3K）、丝氨酸/苏氨酸激酶 1（Akt1）和 smad2/3 在心脏组织中的过度表达以及肿瘤坏死因子受体 1（TNFR1）、磷酸化核因子-κB（p-NF-κB）和转化生长因子β1（TGF-β1）在血管组织中的上调被山奈酚抑制（p<0.05）。综上所述，山奈酚在依赖 NO 的高血压大鼠中具有降压、心脏保护、抗氧化和抗炎作用。山奈酚预防 L-NAME 引起的心血管变化的潜在机制是抑制 TNF-α 途径。
