Limonin ameliorates cardiovascular dysfunction and remodeling in hypertensive rats

柠檬苦素 一氧化氮 氧化应激 内分泌学 化学 内科学 血管紧张素II 炎症 药理学 医学 受体 生物化学
作者
Metee Iampanichakul,Prapassorn Potue,Siwayu Rattanakanokchai,Putcharawipa Maneesai,Juthamas Khamseekaew,Wannapa Settheetham‐Ishida,Poungrat Pakdeechote
出处
期刊:Life Sciences [Elsevier]
卷期号:327: 121834-121834 被引量:2
标识
DOI:10.1016/j.lfs.2023.121834
摘要

Limonin is a tetracyclic triterpenoid isolated from citrus fruits. Here, the effects of limonin on cardiovascular abnormalities in nitric oxide-deficient rats induced by Nω-Nitrol-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 (gp91phox) 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 gp91phox protein expression in cardiac and aortic tissue.
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