Limonin ameliorates cardiovascular dysfunction and remodeling in hypertensive rats.

Limonin is a tetracyclic triterpenoid isolated from citrus fruits. Here, the effects of limonin on cardiovascular abnormalities in nitric oxide-deficient rats induced by N 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 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

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Declaration of competing interest The authors declare that they have no conflicts of interest.