Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
Faculty of Veterinary Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
Life Sci. 2023 Aug 15;327:121834. doi: 10.1016/j.lfs.2023.121834. Epub 2023 Jun 7.
Limonin is a tetracyclic triterpenoid isolated from citrus fruits. Here, the effects of limonin on cardiovascular abnormalities in nitric oxide-deficient rats induced by NNitrol-arginine methyl ester (L-NAME) were explored.
Male Sprague Dawley rats were given L-NAME (40 mg/kg, drinking water) for 3 weeks and then treated daily with polyethylene glycol (vehicle), limonin (50 or 100 mg/kg) or telmisartan (10 mg/kg) for two weeks.
Limonin (100 mg/kg) markedly reduced L-NAME-induced hypertension, cardiovascular dysfunction and remodeling in rats (P < 0.05). Increases in systemic angiotensin-converting enzyme (ACE) activity and angiotensin II (Ang II) and a reduction in circulating ACE2 were restored in hypertensive rats treated with limonin (P < 0.05). Reductions in antioxidant enzymes and nitric oxide metabolites (NOx) and increases in oxidative stress components induced by L-NAME were relieved by limonin treatment (P < 0.05). Limonin suppressed the increased expression of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 in cardiac tissue and circulating TNF-α in rats that received L-NAME (P < 0.05). Changes in Ang II receptor type I (AT1R), Mas receptor (MasR), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB) and NADPH oxidase subunit 2 (gp91) protein expression in cardiac and aortic tissue were normalized by limonin (P < 0.05).
In conclusion, limonin ameliorated L-NAME-induced hypertension, cardiovascular dysfunction and remodeling in rats. These effects were relevant to restorations of the renin-angiotensin system, oxidative stress and inflammation in NO-deficient rats. The molecular mechanisms are associated with the modulation of AT1R, MasR, NF-ĸB and gp91 protein expression in cardiac and aortic tissue.
柠烯是一种从柑橘类水果中分离出来的四环三萜。本研究旨在探讨柠烯对一氧化氮缺乏型大鼠（由 NNitrol-精氨酸甲酯诱导）心血管异常的影响。
雄性 Sprague Dawley 大鼠给予 L-NAME（40mg/kg，饮用水）3 周，然后每天用聚乙二醇（载体）、柠烯（50 或 100mg/kg）或替米沙坦（10mg/kg）治疗 2 周。
柠烯（100mg/kg）可显著降低 L-NAME 诱导的高血压、心血管功能障碍和大鼠重塑（P<0.05）。在高血压大鼠中，柠烯可恢复系统血管紧张素转换酶（ACE）活性和血管紧张素 II（Ang II）的升高以及循环 ACE2 的降低（P<0.05）。柠烯可减轻 L-NAME 引起的抗氧化酶和一氧化氮代谢物（NOx）的降低以及氧化应激成分的增加（P<0.05）。柠烯可抑制心肌组织和循环中 TNF-α 在 L-NAME 处理大鼠中的表达增加（P<0.05）。在心脏和主动脉组织中，柠烯可使 Ang II 受体 1 型（AT1R）、Mas 受体（MasR）、核因子 kappa-轻链增强子的激活 B 细胞（NF-ĸB）和 NADPH 氧化酶亚基 2（gp91）蛋白表达的变化正常化（P<0.05）。
总之，柠烯改善了 L-NAME 诱导的高血压、心血管功能障碍和大鼠重塑。这些作用与恢复缺乏一氧化氮的大鼠肾素-血管紧张素系统、氧化应激和炎症有关。分子机制与心脏和主动脉组织中 AT1R、MasR、NF-ĸB 和 gp91 蛋白表达的调节有关。
