1,721,187 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
No full textStevia 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
Pharmacological modulation of the hydrogen sulfide (H2S) system by dietary H2S-donors: A novel promising strategy in the prevention and treatment of type 2 diabetes mellitus
No full textType 2 diabetes mellitus (T2DM) represents the most common age-related metabolic disorder, and its management is becoming both a health and economic issue worldwide. Moreover, chronic hyperglycemia represents one of the main risk factors for cardiovascular complications. In the last years, the emerging evidence about the role of the endogenous gasotransmitter hydrogen sulfide (H2S) in the pathogenesis and progression of T2DM led to increasing interest in the pharmacological modulation of endogenous “H2S-system”. Indeed, H2S directly contributes to the homeostatic maintenance of blood glucose levels; moreover, it improves impaired angiogenesis and endothelial dysfunction under hyperglycemic conditions. Moreover, H2S promotes significant antioxidant, anti-inflammatory, and antiapoptotic effects, thus preventing hyperglycemia-induced vascular damage, diabetic nephropathy, and cardiomyopathy. Therefore, H2S-releasing molecules represent a promising strategy in both clinical management of T2DM and prevention of macro- and micro-vascular complications associated to hyperglycemia. Recently, growing attention has been focused on dietary organosulfur compounds. Among them, garlic polysulfides and isothiocyanates deriving from Brassicaceae have been recognized as H2S-donors of great pharmacological and nutraceutical interest. Therefore, a better understanding of the therapeutic potential of naturally occurring H2S-donors may pave the way to a more rational use of these nutraceuticals in the modulation of H2S homeostasis in T2DM
Emerging role of the cardiac lipidome in the progression of heart failure.
No full textLipids 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
Targeting Opioid Receptors in Addiction and Drug Withdrawal: Where Are We Going?
Full text linkThis review article offers an outlook on the use of opioids as therapeutics for treating several diseases, including cancer and non-cancer pain, and focuses the analysis on the opportunity to target opioid receptors for treating opioid use disorder (OUD), drug withdrawal, and addiction. Unfortunately, as has been well established, the use of opioids presents a plethora of side effects, such as tolerance and physical and physiological dependence. Accordingly, considering the great pharmacological potential in targeting opioid receptors, the identification of opioid receptor ligands devoid of most of the adverse effects exhibited by current therapeutic agents is highly necessary. To this end, herein, we analyze some interesting molecules that could potentially be useful for treating OUD, with an in-depth analysis regarding in vivo studies and clinical trials
Combinatorial approaches for novel cardiovascular drug discovery: a review of the literature
No full textIntroduction: In this article, authors report an inclusive discussion about the combinatorial approach for the treatment of cardiovascular diseases (CVDs) and for counteracting the cardiovascular risk factors. The mentioned strategy was demonstrated to be useful for improving the efficacy of pharmacological treatments and in CVDs showed superior efficacy with respect to the classical monotherapeutic approach. Areas covered: According to this topic, authors analyzed the combinatorial treatments that are available on the market, highlighting clinical studies that demonstrated the efficacy of combinatorial drug strategies to cure CVDs and related risk factors. Furthermore, the review gives an outlook on the future perspective of this therapeutic option, highlighting novel drug targets and disease models that could help the future cardiovascular drug discovery Expert opinion: The use of specifically designed and increasingly rational and effective drug combination therapies can therefore be considered the evolution of polypharmacy in cardiometabolic and CVDs. This approach can allow to intervene on multiple etiopathogenetic mechanisms of the disease or to act simultaneously on different pathologies/risk factors, using the combinations most suitable from a pharmacodynamic, pharmacokinetic, and toxicological perspective, thus finding the most appropriate therapeutic option
Recent efforts in drug discovery on vascular inflammation and consequent atherosclerosis
No full textIntroduction: Preservation of vascular endothelium integrity and maintenance of its full functionality are fundamental aspects in order to avoid both cardiovascular and non-cardiovascular diseases. Areas covered: Although a massive endothelial disruption is a rare condition, caused by acute and uncontrolled inflammatory responses (e.g. the cytokine storm induced by SARS-CoV-2 infection), more frequently the vascular tree is the first target of slowly progressive inflammatory processes which affect the integrity of endothelium and its ‘barrier’ function, supporting the onset of atherosclerotic plaque and spreading inflammation. This endothelial dysfunction leads to decrease NO biosynthesis, impaired regulation of vascular tone, and increased platelet aggregation. Such chronic subclinic inflammation leads to macrophage infiltration in atherosclerotic lesions. Therefore, many efforts should be addressed to find useful approaches to preserve vascular endothelium from inflammation. In this review, the authors have evaluated the most recent strategies to counteract this pathological condition. Expert opinion: The therapeutic and nutraceutical approaches represent useful tools to treat or prevent different phases of vascular inflammation. In particular, the pharmacological approach should be used in advanced phases characterized by clinical signs of vascular disease, whilst the nutraceutical approach may represent a promising preventive strategy to preserve the integrity of the endothelial tissue
Improving curcumin bioavailability: Current strategies and future perspectives
No full textCurcumin possesses a plethora of interesting pharmacological effects. Unfortunately, it is also characterized by problematic drug delivery and scarce bioavailability, representing the main problem related to the use of this compound. Poor absorption, fast metabolism, and rapid systemic clearance are the most important factors contributing to low curcumin levels in plasma and tissues. Accordingly, to overcome these issues, numerous strategies have been proposed and are investigated in this article. Due to advances in the drug delivery field, we describe here the most promising strategies for increasing curcumin bioavailability, including the use of adjuvant, complexed/encapsulated curcumin, specific curcumin formulations, and curcumin nanoparticles. We analyze current strategies, already available in the market, and the most advanced technologies that can offer a future perspective for effective curcumin formulations. We focus the attention on the effectiveness of curcumin-based formulations in clinical trials, providing a comprehensive summary. Clinical trial results, employing various delivery methods for curcumin, showed that improved bioavailability corresponds to increased therapeutic efficacy. Furthermore, advances in the field of nanoparticles hold great promise for developing curcumin-based complexes as effective therapeutic agents. Summarizing, suitable delivery methods for this polyphenol will ensure the possibility of using curcumin-derived formulations in clinical practice as preventive and disease-modifying therapeutics
Computation to Fight SARS-CoV-2 (COVID-19)
No full textIn April 2020, during the last pandemic health emergency, we launched a Special Issue hosted by Computation—section Computational Biology, entitled “Computation to Fight SARS-CoV-2 (COVID-19)” [...
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