Imperatorin attenuates cardiac remodelling and dysfunction in high-fat/high-fructose diet-fed rats by modulating oxidative stress, inflammation, and Nrf-2 expression.

Imperatorin, an active natural furocoumarin, exerts a wide range of biological activities. In the present study, the therapeutic effects of imperatorin on cardiac function and remodelling and the possible underlying mechanisms involved in high-fat/high-fructose diet (HFFD)-fed rats were investigated. Male Sprague-Dawley rats were fed a high-fat diet plus 15 % fructose in drinking water for 16 weeks. HFFD-fed rats were treated with imperatorin (15 or 30 mg/kg/day) for the last 4 weeks. Treatment of HFFD-fed rats with imperatorin significantly reduced dyslipidaemia, hyperinsulinaemia, and hypertension. Imperatorin markedly alleviated HFFD-induced cardiac morphology alterations and left ventricular (LV) dysfunction. Imperatorin also significantly decreased malondialdehyde concentration and increased catalase activity in plasma and cardiac tissue. Additionally, decreased plasma tumour necrosis factor-α and interleukin-6 concentrations, together with restoration of cardiac nuclear factor-erythroid 2-related factor 2 (Nrf-2) protein expression, were also observed after treatment with imperatorin. These findings indicated that imperatorin alleviates HFFD-induced cardiac remodelling and LV dysfunction in rats. The possible underlying mechanism may involve the reduction of oxidative stress and inflammation, and the restoration of Nrf-2 expression.

Hesperidin Suppresses Renin-Angiotensin System Mediated NOX2 Over-Expression and Sympathoexcitation in 2K-1C Hypertensive Rats.

Hesperidin, a flavonoid derived from citrus fruits, possesses several beneficial effects including anti-oxidation and anti-inflammation. The aim of this study was to investigate the effects of hesperidin on the renin-angiotensin system (RAS) cascade that mediated oxidative stress and sympathoexcitation in two-kidney, one-clipped (2K-1C) hypertensive rats. 2K-1C hypertension was induced in male Sprague-Dawley rats. Hypertensive rats were treated with hesperidin at 20[Formula: see text]mg/kg or 40[Formula: see text]mg/kg or losartan at 10[Formula: see text]mg/kg beginning at three weeks after surgery and then continued for four weeks ([Formula: see text]/group). Hesperidin reduced blood pressure in a dose-dependent manner in hypertensive rats compared to untreated rats ([Formula: see text]). Increased plasma angiotensin converting enzyme (ACE) activity and angiotensin II levels, as well as, upregulated AT1 receptor protein expression in aortic tissues were attenuated in hypertensive rats treated with hesperidin. Hesperidin suppressed oxidative stress markers and NADPH oxidase over-expression, and restored plasma nitric oxide metabolites in 2K-1C rats. This was associated with improvement of the vascular response to acetylcholine in isolated mesenteric vascular beds and aortic rings from 2K-1C rats treated with hesperidin ([Formula: see text]). Enhancement of nerve-mediated vasoconstriction related to high plasma noradrenaline in the 2K-1C group was alleviated by hesperidin treatment ([Formula: see text]). Furthermore, losartan exhibited antihypertensive effects by suppressing the RAS cascade and oxidative stress and improved vascular dysfunction observed in 2K-1C rats ([Formula: see text]). Based on these results, it can be presumed that hesperidin is an antihypertensive agent. Its antihypertensive action might be associated with reducing RAS cascade-induced NOX2 over-expression and sympathoexcitation in 2K-1C hypertensive rats.