Pharmacological modulation of vascular ageing: A review from VascAgeNet.

Vascular ageing, characterized by structural and functional changes in blood vessels of which arterial stiffness and endothelial dysfunction are key components, is associated with increased risk of cardiovascular and other age-related diseases. As the global population continues to age, understanding the underlying mechanisms and developing effective therapeutic interventions to mitigate vascular ageing becomes crucial for improving cardiovascular health outcomes. Therefore, this review provides an overview of the current knowledge on pharmacological modulation of vascular ageing, highlighting key strategies and promising therapeutic targets. Several molecular pathways have been identified as central players in vascular ageing, including oxidative stress and inflammation, the renin-angiotensin-aldosterone system, cellular senescence, macroautophagy, extracellular matrix remodelling, calcification, and gasotransmitter-related signalling. Pharmacological and dietary interventions targeting these pathways have shown potential in ameliorating age-related vascular changes. Nevertheless, the development and application of drugs targeting vascular ageing is complicated by various inherent challenges and limitations, such as certain preclinical methodological considerations, interactions with exercise training and sex/gender-related differences, which should be taken into account. Overall, pharmacological modulation of endothelial dysfunction and arterial stiffness as hallmarks of vascular ageing, holds great promise for improving cardiovascular health in the ageing population. Nonetheless, further research is needed to fully elucidate the underlying mechanisms and optimize the efficacy and safety of these interventions for clinical translation.

Protective effects of wheat germ oil against erectile and endothelial dysfunction in streptozotocin-induced diabetic rats.

Our aim was to investigate the protective effect of wheat germ oil (WGO) at different doses on diabetes mellitus (DM)-induced erectile and endothelial dysfunction. Twenty-four male Wistar rats weighing 250-300 g were divided into four groups as; control group treated with saline, DM group, DM group treated with 3 ml/kg WGO (DM + 3WGO group), DM group treated with 6 ml/kg WGO. Type 1 DM was induced by intraperitoneal injection of 60 mg/kg streptozotocin (STZ). STZ-induced diabetic rats received saline, 3 ml/kg WGO, and 6 ml/kg WGO via oral gavage daily for 5 weeks. The density of WGO used was 0.92 g/ml. The protective effect of WGO was evaluated by (i) in vitro vascular function, (ii) in vivo erectile function, and (iii) oxidative stress parameters in both aorta and penile tissue. Acetylcholine-mediated relaxation in the aorta and erectile functions decreased significantly in the DM group (p = 0.018 and p = 0.005). WGO (3 and 6 ml/kg) improved vascular functions in the DM groups (p = 0.001 and p = 0.014). The beneficial effect of WGO on erectile function appeared at higher doses of WGO. However, a higher dose of WGO substantially increased the oxidative stress parameters in both aorta and penile tissue. These findings suggest that the improvement in vascular or erectile function by WGO was not related to antioxidant effects, and new studies are needed to clarify the mechanism.

A Comparison of the Effectiveness of Silibinin and Resveratrol in Preventing Alpha-Amanitin-Induced Hepatotoxicity.

Amanita phalloides species mushrooms containing alpha-amanitin (α-AMA) are responsible for the majority of fatal mushroom intoxications and can lead to severe poisonings resulting in hepatotoxicity and acute hepatic failure. Existing antidotes, such as silibinin, are not sufficiently effective in the prevention and/or resolution of α-AMA-induced hepatotoxicity. We investigated the effects of resveratrol on α-AMA-induced hepatotoxicity and compared with silibinin, a known antidote using in vivo and in vitro toxicity models. In the in vivo protocol, resveratrol (30 mg/kg) was given simultaneously with α-AMA (α-AMA + SR) or 12 (α-AMA + 12R) or 24 (α-AMA + 24R) hr after α-AMA administration. Silibinin (5 mg/kg) (α-AMA + Sil) and normal saline (α-AMA + NS) were given simultaneously with α-AMA. We found that liver transaminase levels in α-AMA + SR and α-AMA + 12R groups and histomorphologic injury score in the α-AMA + SR, α-AMA + 12R, α-AMA + 24R and α-AMA + Sil groups were significantly lower than that of the α-AMA + NS group. Resveratrol decreased mononuclear cell infiltration, necrosis and active caspase-3 immunopositivity in the liver. In the in vitro protocol, the effects of resveratrol and silibinin were evaluated in a reduction in cell viability induced by α-AMA in THLE-2 and THLE-3 hepatocytes. Neither resveratrol nor silibinin was found to be effective in increasing cell viability decreased by α-AMA + NS. As a conclusion, resveratrol was found to be effective in α-AMA-induced hepatotoxicity with its anti-inflammatory properties in in vivo conditions. It is a promising compound with the potential for use in the treatment of hepatotoxicity associated with Amanita phalloides type mushroom poisonings.