Diosmetin Ameliorates Vascular Dysfunction and Remodeling by Modulation of Nrf2/HO-1 and p-JNK/p-NF-κB Expression in Hypertensive Rats

Abstract

Diosmetin is a citrus flavonoid that has antioxidant and anti-inflammatory effects. This study examined the effect of diosmetin on blood pressure and vascular alterations and its underlying mechanisms in experimentally hypertensive rats. Male Sprague rats were administered Nω-nitro-L-arginine methyl ester L-NAME for five weeks and were given diosmetin at doses of 20 or 40 mg/kg or captopril (5 mg/kg) for two weeks. Diosmetin alleviated hypertension, improved endothelial dysfunction, and suppressed the overactivity of sympathetic nerve-mediated vasoconstriction in aorta and mesentery hypertensive rats (p < 0.05). Increases in plasma and aortic tissue malondialdehyde (MDA) and carotid superoxide generations and reductions of plasma superoxide dismutase, catalase, and nitric oxide in hypertensive rats were ameliorated by diosmetin (p < 0.05). Diosmetin increased the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in hypertensive rats. Furthermore, diosmetin mitigated hypertrophy and collagen accumulation of the aortic wall in L-NAME rats. It exhibited an anti-inflammatory effect by reducing interleukin-6 (IL-6) accumulation and by overexpressing the phospho-c-Jun N-terminal kinases (p-JNK) and the phospho-nuclear factor-kappaB (p-NF-κB) proteins in the aorta (p < 0.05). Captopril was a positive control substance and had similar effects to diosmetin. In summary, diosmetin reduced blood pressure and alleviated vascular abnormalities in L-NAME-treated rats. These effects might be related to antioxidant and anti-inflammatory effects as well as to the modulation of the expression of the Nrf2/HO1 and p-JNK/NF-κB proteins.

Oxidative Stress in the Pathogenesis of Aorta Diseases as a Source of Potential Biomarkers and Therapeutic Targets, with a Particular Focus on Ascending Aorta Aneurysms

“…They are generally utilized as functional foods, soft drinks, and many other food items, and show good nutritional value [ 59 , 60 ]. In animal AsAA models, their action has been revealed to be effective, while human clinical trial studies have failed to demonstrate this evidence [ 61 , 62 , 63 , 64 , 65 , 66 , 67 ]. Davies and Holt, by adopting two modelling techniques, namely Gillespie’s Stochastic Simulation Algorithm (using Kinetiscope) and a discrete Markov chain, have showed the diverse reasons for this failure, including the rate of reaction between the free radicals and the non-enzymatic antioxidants, which is considered a necessary threshold for evaluating the effect of an antioxidant on the free radical defence systems naturally present, making it able to minimise their action [ 63 ].…”

“…Diosmetin is a citrus flavonoid with antioxidant and anti-inflammatory effects. Experimental studies have shown its ability to ameliorate vascular dysfunction and remodelling by influencing the expression of Nrf2/HO-1 and p-JNK/p-NF-κB in hypertensive rats [ 65 ]. Other natural compounds explored in recent examinations include, for example, essential oils, which represent alternatives to natural and synthetic antioxidant agents [ 66 , 67 ].…”

The Role of NRF2 in Obesity-Associated Cardiovascular Risk Factors

“…Diosmetin is a citrus flavonoid with antioxidant and anti-inflammatory effects. Diosmetin improved hypertension, endothelial dysfunction by modulation of NRF2/HO-1, and p-JNK/p-NF-κB expression in hypertensive rats [ 147 ]. Irisin is an exercise-induced myokine, and it was reported that intravenous injection of irisin in an SHR model reduced BP, plasma norepinephrine, paraventricular nucleus (PVN) levels of neuronal activation, oxidative stress, and inflammation by activating the NRF2 signaling pathway in the hypothalamic paraventricular nucleus [ 148 ].…”

Probiotics Bring New Hope for Atherosclerosis Prevention and Treatment

“…NO is a soluble gas with vasodilator promoting functions, as well as anti-inflammatory and antioxidant properties that can play an important role in maintaining vascular homeostasis [ 53 , 54 ]. Decreased production and sensitivity of NO can lead to imbalance of vascular homeostasis and thrombosis, thereby potentially facilitating the progression of AS [ 55 ].…”