Limonin alleviates macro- and micro-vascular complications of metabolic syndrome in rats: A comparative study with azelnidipine

Background: Hypertension is a serious component of metabolic syndrome (MetS). Hypothesis: This research investigates the potential protective effect of limonin against MetS-associated hypertension in comparison with azelnidipine, a common calcium channel blocker. Study design: MetS was induced in rats by 10% fructose in water and 3% salt in diet over a 16-week period. Limonin (50 mg/kg) and azelnidipine (5 mg/kg) were administered daily in the last four weeks Methods: Non-invasive blood pressure (BP) was recorded in conscious animals. Concentration-response curves for phenylephrine (PE) and acetylcholine (ACh) were analysed in thoracic aorta (macrovessels) and kidney microvessels. Blood glucose level, serum insulin level, advanced glycation end products (AGEs), tumor necrosis factor-alpha (TNF alpha), malondialdehyde (MDA) and transforming growth factor-beta (TGF-beta 1) were determined. Results: Limonin alleviated elevations in systolic and diastolic BP associated with MetS similar to levels associated with azelnidipine. Limonin prevented the MetS induced exaggerated macro- and micro-vascular contractility to PE and the impaired dilatation to ACh. However, in vitro incubation with limonin partially alleviated the deteriorated vascular reactivity of aorta isolated from MetS animals or AGEs injured aorta. Limonin did not have direct relaxant effect on the isolated vessel. On the other hand, limonin reduced the elevated serum levels of AGEs, TNF-alpha and MDA. Limonin suppressed the vascular fibrosis through reducing the elevated serum level of TGF-beta 1 and excessive aortic collagen deposition. Limonin decreased the elevated HOMA-IR in MetS animals. Conclusion: Limonin offsets the hypertensive and vascular impairment associated with MetS via attenuation of inflammation and fibrosis. Its impact is comparable to that of azelnidipine.