Thymoquinone improves aging-related endothelial dysfunction in the rat mesenteric artery

Abstract

Aging-related endothelial dysfunction is characterized by blunted nitric oxide (NO)- and endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxations in arteries, which may be due, at least in part, to increased oxidative stress. Endothelial dysfunction will promote the initiation and development of major cardiovascular diseases such as atherosclerosis and hypertension. Thymoquinone (TQ) is the most active constituent of the volatile oil of Nigella sativa seeds with well-documented antioxidative properties and vasodilator effects. This study determined whether TQ improves the endothelial function in middle-aged rats. Control young rats (16 weeks) received solvent (ethanol, 3% v/v), and middle-aged rats (46 weeks) either solvent or TQ (10 mg/kg/day) in the drinking water. Mesenteric artery reactivity was determined in organ chambers, vascular oxidative stress by dihydroethidine and MitoSOX staining, and expression of target proteins by immunohistochemical staining. Aging-related blunted NO- and EDHF-mediated responses were associated with downregulation of endothelial NO synthase (eNOS) and calcium-activated potassium channels (SK(Ca) and IK(Ca)) expression. Endothelial dysfunction was also associated with oxidative stress and an upregulation of angiotensin II and AT1 receptor expressions. Intake of TQ for 14 days restored NO- and EDHF-mediated relaxations, normalized oxidative stress, the expression level of eNOS, SK(Ca), IK(Ca), and the components of the angiotensin system in the mesenteric artery of middle-aged rats. Thus, TQ improves endothelial function in aging, at least in part, through inhibition of oxidative stress and normalization of the angiotensin system. TQ may represent a novel therapeutic approach for aging-associated vascular diseases.

Effects of Selected Bioactive Natural Products on the Vascular Endothelium

“…106 A recent study showed that TQ improves aging-related endothelial dysfunction in the rat mesenteric artery. 107 The study was carried out on 12 middle-aged (46 weeks) male Wistar rats divided into 2 groups of 6 rats receiving either solvent (3% ethanol vol/vol) or TQ (10 mg/kg per day) in the drinking water for 14 days. Six male Wistar rats (16 weeks old) were used as young controls.…”

“…Overall, these research findings specify that TQ improved aging-related endothelial dysfunction most likely by preventing oxidative stress and normalizing the angiotensin system. 107 Hawthorn extract (Crataegus ssp.) is a rich source of polyphenols, including a mixture of monomeric flavonoids and oligomeric procyanidins (OPCs).…”

“…Interestingly, it has been shown that the Crataegus extract is a potent inducer of NO-and EDHF-mediated relaxations of coronary artery rings. 109 In another study, 107 Wistar rats were treated with either a control diet or the same diet containing 100 or 300 mg/kg per day of Crataegus extract from week 25 until week 65. Vascular reactivity was assessed in mesenteric artery rings using organ chambers, oxidative stress by DHE staining, and COX-1 and COX-2 expressions by immunohistochemistry.…”

“…An excessive vascular oxidative stress and an upregulation of COX-1 and COX-2 were observed in the mesenteric artery of old rats compared with young rats, and these effects were improved by the Crataegus treatment. 107 …”

Endothelium-Dependent Contractions of Isolated Arteries to Thymoquinone Require Biased Activity of Soluble Guanylyl Cyclase with Subsequent Cyclic IMP Production

“…In mice, it protects against sepsis-induced morbidity and mortality (Alkharfy et al, 2011), and in rats, its chronic administration improves age-related endothelial dysfunction (Idris-Khodja and Schini-Kerth, 2012). In preliminary experiments on isolated rat arteries, aimed at investigating the vasodilator properties of thymoquinone, a serendipitous finding was that the compound actually augmented sustained contractions in preparations with endothelium ( Fig.…”