1,721,033 research outputs found
CHAPTER 8: Stevia rebaudiana Bertoni: Beyond Its Use as a Sweetener. Pharmacological and Toxicological Profile of Steviol Glycosides of Stevia rebaudiana Bertoni
Stevia rebaudiana Bertoni is a plant originating in Paraguay that is well-known for the sweet taste of its leaves. Stevia extract is widely used as a substitute for sucrose, it contains more than 10 compounds, called steviol glycosides (SGs), of which the best characterised are stevioside and rebaudioside A. All steviol glycosides need a bioactivation by intestinal bacteria, through which they are converted to steviol, the active metabolite. Indeed, the pharmacodynamic profile of stevia extract and steviol glycosides is related to steviol. A number of animal studies and clinical trials have been performed to investigate the effects of SGs, mostly of stevioside and rebaudioside A, observing that, beside the sweet taste, these natural derivatives may offer a multitude of beneficial effects on health. Indeed, growing evidence points to a nutraceutical use of Stevia rebaudiana Bertoni and its SGs. Moreover, an examination of toxicological profiles and adverse effects carried out from regulatory agencies in order to authorise its commercialisation as a sweetener has been here reported
Emerging role of the cardiac lipidome in the progression of heart failure.
Lipids play structural and cellular functions, being a part of cellular membranes, regulating signaling, transmembrane transporters and energy depots. The lipid profile is not static, and a large number of human pathologies have been linked to alterations of lipid homeostasis, including cancer, neurodegenerative, cardiovascular and metabolic diseases. Among the cardiovascular diseases, an altered lipid metabolism has been implicated in heart failure (HF). Based on the recent evidence, changes in the levels of some specific lipids reflect the progression of cardiovascular diseases and, interestingly, their alterations can also occur independently from obesogenic stimuli. In this review, evidence of lipotoxicity at cardiac level will be reported discriminating between clinical or preclinical evidence and the presence or absence of obesogenic conditions. In numerous experimental models, both with and without obesity, ceramides (CERs) and triacyclglycerols (TAGs) levels increased at the cardiac level and were associated with a higher risk of cardiovascular diseases and directly correlated with their severity. Conversely, cardiolipin (CL), the peculiar phospholipid of the inner mitochondrial membrane, is inversely related to cardiovascular risk, and it is considered a crucial factor responsible for the regulation of mitochondrial function and therefore useful as an early marker of prodromal changes driving the cardiac contractility alterations. Most of the progress in this field has probably focused on this lipid: aimed at the development of synthetic analogues useful for mimicking the role of CLs, in order to restore its physiological function; but also, to the discovery of compounds capable of specifically bind CL, useful as diagnostic tools
Role of mitochondrial potassium channels in ageing
Ageing is described as an inevitable decline in body functions over time and an increase in susceptibility to agerelated diseases. Therefore, the increase of life expectancy is also viewed as a condition in which many elderly will develop age-related diseases and disabilities, such as cardiovascular, metabolic, neurological and oncological ones. Currently, several recognized cellular hallmarks of senescence are taken in consideration to evaluate the level of biological ageing and are the topic to plan preventive/curative anti-ageing interventions, including genomic instability, epigenetic alterations, and mitochondrial dysfunction. In this scenario, alterations in the function/expression of mitochondrial ion channels have been found in ageing and associated to an impairment of calcium cycling and a reduced mitochondrial membrane potential. Although several ion channels have been described at mitochondrial level, undoubtedly the mitochondrial potassium (mitoK) channels are the most investigated. Therefore, this review summarized the evidence that sheds to light a correlation between agerelated diseases and alteration of mitoK channels, focusing the attention of the main age-related diseases, i.e. cardiovascular, neurological and oncological ones
Modulation of endmt by hydrogen sulfide in the prevention of cardiovascular fibrosis
Endothelial mesenchymal transition (EndMT) has been described as a fundamental process during embryogenesis; however, it can occur also in adult age, underlying pathological events, including fibrosis. Indeed, during EndMT, the endothelial cells lose their specific markers, such as vascular endothelial cadherin (VE-cadherin), and acquire a mesenchymal phenotype, expressing specific products, such as α-smooth muscle actin (α-SMA) and type I collagen; moreover, the integrity of the endothelium is disrupted, and cells show a migratory, invasive and proliferative phenotype. Several stimuli can trigger this transition, but transforming growth factor (TGF-β1) is considered the most relevant. EndMT can proceed in a canonical smad-dependent or non-canonical smadindependent manner and ultimately regulate gene expression of pro-fibrotic machinery. These events lead to endothelial dysfunction and atherosclerosis at the vascular level as well as myocardial hypertrophy and fibrosis. Indeed, EndMT is the mechanism which promotes the progression of cardiovascular disorders following hypertension, diabetes, heart failure and also ageing. In this scenario, hydrogen sulfide (H2S) has been widely described for its preventive properties, but its role in EndMT is poorly investigated. This review is focused on the evaluation of the putative role of H2S in the EndMT process
Role of hydrogen sulfide in cardiovascular ageing
Cardiovascular diseases are the main cause of morbidity and mortality in the Western society and ageing is a relevant non-modifiable risk factor. Morphological and functional alterations at endothelial level represent first events of ageing, inevitably followed by vascular dysfunction and consequent atherosclerosis that deeply influences cardiovascular health. Indeed, myocardial hypertrophy and fibrosis typically occur and contribute to compromise overall cardiac output. As regards the intracellular molecular mechanisms involved in the cardiovascular ageing, an intricate network is emerging, revealing a role for many mediators, including SIRT1/AMPK/PCG1α pathway, anti-oxidants factors (i.e. Nrf-2 and FOXOs) and pro-inflammatory cytokines. Thus, the search for pharmacological and non-pharmacological strategies that can promote a "healthy ageing", in order to slow down age-related machinery, are currently an exciting challenge for the biomedical research. Interestingly, hydrogen sulfide (H2S) has been recently recognized as a new player capable to influence intracellular machinery involved in ageing and then it is view as a potential target for preventing cardiovascular diseases. Therefore, this review is focused on the role of H2S in cardiovascular ageing, and on the evidence of the relationship between progressive decline in endogenous H2S levels and the onset of various cardiovascular age-related diseases
Coenzyme Q10: Clinical applications in cardiovascular diseases
Coenzyme Q10 (CoQ10) is a ubiquitous factor present in cell membranes and mitochondria, both in its reduced (ubiquinol) and oxidized (ubiquinone) forms. Its levels are high in organs with high metabolism such as the heart, kidneys, and liver because it acts as an energy transfer molecule but could be reduced by aging, genetic factors, drugs (e.g., statins), cardiovascular (CV) diseases, degenerative muscle disorders, and neurodegenerative diseases. As CoQ10 is endowed with significant antioxidant and anti-inflammatory features, useful to prevent free radical-induced damage and inflammatory signaling pathway activation, its depletion results in exacerbation of inflammatory processes. Therefore, exogenous CoQ10 supplementation might be useful as an adjuvant in the treatment of cardiovascular diseases such as heart failure, atrial fibrillation, and myocardial infarction and in associated risk factors such as hypertension, insulin resistance, dyslipidemias, and obesity. This review aims to summarize the current evidences on the use of CoQ10 supplementation as a therapeutic approach in cardiovascular diseases through the analysis of its clinical impact on patients’ health and quality of life. A substantial reduction of inflammatory and oxidative stress markers has been observed in several randomized clinical trials (RCTs) focused on several of the abovementioned diseases, even if more RCTs, involving a larger number of patients, will be necessary to strengthen these interesting findings
Hydrogen Sulfide and Irisin, Potential Allies in Ensuring Cardiovascular Health
Irisin is a myokine secreted under the influence of physical activity and exposure to low temperatures and through different exogenous stimuli by the cleavage of its precursor, fibronectin type III domain-containing protein 5 (FNDC5). It is mainly known for maintaining of metabolic homeostasis, promoting the browning of white adipose tissue, the thermogenesis process, and glucose homeostasis. Growing experimental evidence suggests the possible central role of irisin in the regulation of cardiometabolic pathophysiological processes. On the other side, hydrogen sulfide (H2S) is well recognized as a pleiotropic gasotransmitter that regulates several homeostatic balances and physiological functions and takes part in the pathogenesis of cardiometabolic diseases. Through the S-persulfidation of cysteine protein residues, H2S is capable of interacting with crucial signaling pathways, exerting beneficial effects in regulating glucose and lipid homeostasis as well. H2S and irisin seem to be intertwined; indeed, recently, H2S was found to regulate irisin secretion by activating the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)/FNDC5/irisin signaling pathway, and they share several mechanisms of action. Their involvement in metabolic diseases is confirmed by the detection of their lower circulating levels in obese and diabetic subjects. Along with the importance of metabolic disorders, these modulators exert favorable effects against cardiovascular diseases, preventing incidents of hypertension, atherosclerosis, heart failure, myocardial infarction, and ischemia–reperfusion injury. This review, for the first time, aims to explore the role of H2S and irisin and their possible crosstalk in cardiovascular diseases, pointing out the main effects exerted through the common molecular pathways involved
Coenzyme Q10: Clinical Applications beyond Cardiovascular Diseases
Coenzyme Q10 (CoQ10) is an essential cofactor in oxidative phosphorylation (OXPHOS), present in mitochondria and cell membranes in reduced and oxidized forms. Acting as an energy transfer molecule, it occurs in particularly high levels in the liver, heart, and kidneys. CoQ10 is also an anti-inflammatory and antioxidant agent able to prevent the damage induced by free radicals and the activation of inflammatory signaling pathways. In this context, several studies have shown the possible inverse correlation between the blood levels of CoQ10 and some disease conditions. Interestingly, beyond cardiovascular diseases, CoQ10 is involved also in neuronal and muscular degenerative diseases, in migraine and in cancer; therefore, the supplementation with CoQ10 could represent a viable option to prevent these and in some cases might be used as an adjuvant to conventional treatments. This review is aimed to summarize the clinical applications regarding the use of CoQ10 in migraine, neurodegenerative diseases (including Parkinson and Alzheimer diseases), cancer, or degenerative muscle disorders (such as multiple sclerosis and chronic fatigue syndrome), analyzing its effect on patients' health and quality of life
- …
