Autophagy is a self‐degradative process that plays a pivotal role in several medical conditions associated with infection, cancer, neurodegeneration, aging, and metabolic disorders. Its interplay ...with cancer development and treatment resistance is complicated and paramount for drug design since an autophagic response can lead to tumor suppression by enhancing cellular integrity and tumorigenesis by improving tumor cell survival. In addition, autophagy denotes the cellular ability of adapting to stress though it may end up in apoptosis activation when cells are exposed to a very powerful stress. Induction of autophagy is a therapeutic option in cancer and many anticancer drugs have been developed to this aim. Curcumin as a hydrophobic polyphenol compound extracted from the known spice turmeric has different pharmacological effects in both in vitro and in vivo models. Many reports exist reporting that curcumin is capable of triggering autophagy in several cancer cells. In this review, we will focus on how curcumin can target autophagy in different cellular settings that may extend our understanding of new pharmacological agents to overcome relevant diseases.
Autophagy is a self‐degradative process that plays a pivotal role in several medical conditions associated with infection, cancer, neurodegeneration, aging, and metabolic disorders. Curcumin, as a hydrophobic polyphenol compound extracted from the known spice turmeric, is capable of triggering autophagy in several cancer cells.
Non-alcoholic fatty liver disease (NAFLD) is a clinical condition characterized by lipid infiltration of the liver, highly prevalent in the general population affecting 25% of adults, with a doubled ...prevalence in diabetic and obese patients. Almost 1/3 of NAFLD evolves in Non-Alcoholic SteatoHepatitis (NASH), and this can lead to fibrosis and cirrhosis of the liver. However, the main causes of mortality of patients with NAFLD are cardiovascular diseases. At present, there are no specific drugs approved on the market for the treatment of NAFLD, and the treatment is essentially based on optimization of lifestyle. However, some nutraceuticals could contribute to the improvement of lipid infiltration of the liver and of the related anthropometric, haemodynamic, and/or biochemical parameters. The aim of this paper is to review the available clinical data on the effect of nutraceuticals on NAFLD and NAFLD-related parameters. Relatively few nutraceutical molecules have been adequately studied for their effects on NAFLD. Among these, we have analysed in detail the effects of silymarin, vitamin E, vitamin D, polyunsaturated fatty acids of the omega-3 series, astaxanthin, coenzyme Q10, berberine, curcumin, resveratrol, extracts of
, and probiotics. In conclusion, Silymarin, vitamin E and vitamin D, polyunsaturated fatty acids of the omega-3 series, coenzyme Q10, berberine and curcumin, if well dosed and administered for medium⁻long periods, and associated to lifestyle changes, could exert positive effects on NAFLD and NAFLD-related parameters.
Osteoarthritis (OA) is a degenerative inflammatory condition of the joint cartilage that currently affects approximately 58 million adults in the world. It is characterized by pain, stiffness, and a ...reduced range of motion with regard to the arthritic joints. These symptoms can cause in the long term a greater risk of overweight/obesity, diabetes mellitus, and falls and fractures. Although the current guidelines for the treatment of OA suggest, as the gold standard for this condition, pharmacological treatment characterized by non-steroidal anti-inflammatory drugs (NSAID), opioids, and cyclooxygenase (COX)-2-specific drugs, a great interest has been applied to nutraceutical supplements, which include a heterogeneous class of molecules with great potential to reduce inflammation, oxidative stress, pain, and joint stiffness and improve cartilage formation. The purpose of this review is to describe the potential application of nutraceuticals in OA, highlighting its molecular mechanisms of actions and data of efficacy and safety (when available).
There is a direct relationship between fructose intake and serum levels of uric acid (UA), which is the final product of purine metabolism. Recent preclinical and clinical evidence suggests that ...chronic hyperuricemia is an independent risk factor for hypertension, metabolic syndrome, and cardiovascular disease. It is probably also an independent risk factor for chronic kidney disease, Type 2 diabetes, and cognitive decline. These relationships have been observed for high serum UA levels (>5.5 mg/dL in women and >6 mg/dL in men), but also for normal to high serum UA levels (5-6 mg/dL). In this regard, blood UA levels are much higher in industrialized countries than in the rest of the world. Xanthine-oxidase inhibitors can reduce UA and seem to minimize its negative effects on vascular health. Other dietary and pathophysiological factors are also related to UA production. However, the role of fructose-derived UA in the pathogenesis of cardiometabolic disorders has not yet been fully clarified. Here, we critically review recent research on the biochemistry of UA production, the relationship between fructose intake and UA production, and how this relationship is linked to cardiometabolic disorders.
Introduction: Results of previous clinical trials evaluating the effect of resveratrol supplementation on blood pressure (BP) are controversial.
Purpose: We aimed to assess the impact of resveratrol ...on BP through systematic review of literature and meta-analysis of available randomized, controlled clinical trials (RCTs).
Methods: Literature search included SCOPUS, PubMed-Medline, ISI Web of Science and Google Scholar databases up to 17th October 2017 to identify RCTs investigating the impact of resveratrol on BP. Two review authors independently extracted data on study characteristics, methods and outcomes. Overall, the impact of resveratrol on BP was reported in 17 trials.
Results: Administration of resveratrol did not significantly affect neither systolic BP weighted mean difference (WMD): −2.5 95% CI:(-5.5, 0.6) mmHg; p=0.116; I
2
=62.1%, nor diastolic BP WMD: −0.5 95% CI:(-2.2, 1.3) mmHg; p=0.613; I
2
=50.8, nor mean BP MAP; WMD: −1.3 95% CI:(-2.8, 0.1) mmHg; p=0.070; I
2
=39.5% nor pulse pressure PP; WMD: −0.9 95% CI:(-3.1, 1.4) mmHg; p=0.449; I
2
=19.2%. However, significant WMDs were detected in subsets of studies categorized according to high resveratrol daily dosage (≥300 mg/day) and presence of diabetes. Meta-regression analysis revealed a positive association between systolic BP-lowering resveratrol activity (slope: 1.99; 95% CI: 0.05, 3.93; two-tailed p= 0.04) and Body Mass Index (BMI) at baseline, while no association was detected neither between baseline BMI and MAP-lowering resveratrol activity (slope: 1.35; 95% CI: −0.22, 2.91; two-tailed p= 0.09) nor between baseline BMI and PP-lowering resveratrol activity (slope: 1.03; 95% CI: −1.33, 3.39; two-tailed p= 0.39). Resveratrol was fairly well-tolerated and no serious adverse events occurred among most of the eligible trials.
Conclusion: The favourable effect of resveratrol emerging from the current meta-analysis suggests the possible use of this nutraceutical as active compound in order to promote cardiovascular health, mostly when used in high daily dose (≥300 mg/day) and in diabetic patients.
North of Italy was severely hit by the COVID-19 (Coronavirus disease 19) pandemic. This induced the government to adopt severely restrictive measures to reduce the contagion risk, forcing most of the ...population to stop working and from leisure activities, and to remain at home for several weeks. Our study aimed to evaluate the effect of COVID-related quarantine on smoking and dietary habits of a well-characterized northern Italian rural population. For this purpose, while lockdown restrictions were in place (February-April 2020), 359 subjects from the Brisighella Heart Study cohort underwent a phone interview about their lifestyle habit changes during COVID-19-related quarantine. Quarantine did not significantly modify smoking habit nor body mass index. Subjects significantly increased daily carbohydrates consumption, all fresh vegetables, healthy vegetable oils, milk and yogurt, alcoholic drinks, sugars and sweets, and coffee. The weekly consumption of low-fat meat, cured meat other than ham, cheeses, eggs, nuts and mixed seed oils significantly increased, while the weekly intake of fish, mussels, and legumes significantly decreased during lockdown. The Dietary Quality Index was reduced from 42.4 ± 4.1 to 37.8 ± 4.7 (
< 0.03). In accordance with our findings, COVID-19-related quarantine might worsen the quality of diet, also leading to an increased intake of almost all food categories.
Intraplaque release of inflammatory cytokines from macrophages is implicated in atherogenesis by inducing the proliferation and migration of media smooth muscle cells (SMCs). PCSK9 is present and ...released by SMCs within the atherosclerotic plaque but its function is still unknown. In the present study, we tested the hypothesis that PCSK9 could elicit a pro-inflammatory effect on macrophages. THP-1-derived macrophages and human primary macrophages were exposed to different concentrations (0.250 ÷ 2.5 µg/ml) of human recombinant PCSK9 (hPCSK9). After 24 h incubation with 2.5 µg/ml PCSK9, a significant induction of IL-1β, IL-6, TNF-α, CXCL2, and MCP1 mRNA, were observed in both cell types. Co-culture of THP-1 macrophages with HepG2 overexpressing hPCSK9 also showed the induction of TNF-α (2.4 ± 0.5 fold) and IL-1β (8.6 ± 1.8 fold) mRNA in macrophages. The effect of hPCSK9 on TNF-α mRNA in murine LDLR
bone marrow macrophages (BMM) was significantly impaired as compared to wild-type BMM (4.3 ± 1.6 fold vs 31.1 ± 6.1 fold for LDLR
and LDLR
, respectively). Finally, a positive correlation between PCSK9 and TNF-α plasma levels of healthy adult subjects (males 533, females 537) was observed (B = 8.73, 95%CI 7.54 ÷ 9.93, p < 0.001). Taken together, the present study provides evidence of a pro-inflammatory action of PCSK9 on macrophages, mainly dependent by the LDLR.
Cardiovascular diseases (CVDs) are one of the major causes of mortality and disability in Western countries. Prevention is known to be the cornerstone to lessen the incidence of CVDs and also to ...reduce the economic burden of both the citizen and the healthcare system. "Interventional medicine" certainly puts lifestyle modification as the first therapeutic step, including a healthy diet and physical activity. Secondly, a large body of research individuated a number of food and plant bioactives, which are potentially efficacious in preventing and reducing some highly prevalent CV risk factors, such as hypercholesterolemia, hypertension, vascular inflammation and vascular compliance. Some lipid- and blood pressure-lowering bioactives were studied for their impact on human vascular health, particularly as regards endothelial function and arterial stiffness. Several nutraceuticals showed additive or synergistic properties in combination, sometimes (but not always) allowing a reduction of the administered dose of extracts and determining a "multi-factorial" final effect on many cardiovascular risk factors. Thus, this review focuses on available evidence regarding the effects of berberine, plant sterols, green tea extract, soy, curcumin, cocoa, pycnogenol, lycopene, olive oil, soluble fibers, garlic, resveratrol, beetroot, mineral salts and vitamins on the lipid profile, blood pressure, inflammatory and endothelial markers, and vascular compliance. Future clinical research studies will have to focus more on middle term modification of the instrumental markers of vascular aging than on short-term effects on indirect laboratory risk markers.
Purines, such as adenine and guanine, perform several important functions in the cell. They are found in nucleic acids; are structural components of some coenzymes, including NADH and coenzyme A; and ...have a crucial role in the modulation of energy metabolism and signal transduction. Moreover, purines have been shown to play an important role in the physiology of platelets, muscles, and neurotransmission. All cells require a balanced number of purines for growth, proliferation, and survival. Under physiological conditions, enzymes involved in purines metabolism maintain a balanced ratio between their synthesis and degradation in the cell. In humans, the final product of purine catabolism is uric acid, while most other mammals possess the enzyme uricase that converts uric acid to allantoin, which can be easily eliminated with urine. During the last decades, hyperuricemia has been associated with a number of human extra-articular diseases (in particular, the cardiovascular ones) and their clinical severity. In this review, we go through the methods of investigation of purine metabolism dysfunctions, looking at the functionality of xanthine oxidoreductase and the formation of catabolites in urine and saliva. Finally, we discuss how these molecules can be used as markers of oxidative stress.
Berberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids found in such plants as gender Berberis. Berberine is recognised to improve glucose and lipid ...metabolism disorders and preliminary clinical evidences suggest the ability of berberine to reduce endothelial inflammation improving vascular health, even in patients already affected by cardiovascular diseases, suggesting a possible interesting role of berberine and its metabolites in clinical practice. However, its physicochemical properties, pharmacokinetic, and metabolism are not fully elucidated and contradictory data have been reported. This review provides a summary regarding the pharmacological and biological features of berberine, with a focus on berberine as well as their pharmacologically active metabolites and the different mechanisms underlying their activities in order to clarify the correct use of berberine supplementation, alone or in association with other nutraceuticals, for the management of metabolic disorders associated to increased cardiovascular disease risk. A particular attention has also been given to the available clinical trials assessing its short- and middle- term use tolerability, safety and efficacy in various conditions, such as dyslipidaemia, impaired fasting glucose, metabolic syndrome and type 2 diabetes.
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