Limonin ameliorates cardiovascular dysfunction and remodeling in hypertensive rats

Aims: Limonin is a tetracyclic triterpenoid isolated from citrus fruits. Here, the effects of limonin on cardio-vascular abnormalities in nitric oxide-deficient rats induced by N-?-Nitrol-arginine methyl ester (L-NAME) were explored.Main methods: 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.Key findings: 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 sup-pressed the increased expression of tumor necrosis factor-a (TNF-a) and interleukin (IL)-6 in cardiac tissue and circulating TNF-a 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-?B) and NADPH oxidase subunit 2 (gp91(phox)) protein expression in cardiac and aortic tissue were normalized by limonin (P < 0.05).Significance: 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-?B and gp91(phox) protein expression in cardiac and aortic tissue.

Automated summary

This study found that limonin has a beneficial effect on cardiovascular abnormalities in nitric oxide-deficient rats. Limonin can reduce hypertension, improve cardiovascular function, and remodel cardiac tissue. The mechanism of action involves the modulation of proteins related to the renin-angiotensin system, oxidative stress, and inflammation.