Statins are competitive inhibitors of hydroxymethylglutaryl-CoA (HMG-CoA) reductase and have been used to treat elevated low-density lipoprotein cholesterol (LDL-C) for almost four decades. ...Antioxidant and anti-inflammatory properties which are independent of the lipid-lowering effects of statins, i.e., their pleiotropic effects, might be beneficial in the prevention or treatment of many diseases. This review discusses the antioxidant effects of statins achieved by modulating the nuclear factor erythroid 2 related factor 2/ heme oxygenase-1 (Nrf2/HO-1) pathway in different organs and diseases. Nrf2 and other proteins involved in the Nrf2/HO-1 signaling pathway have a crucial role in cellular responses to oxidative stress, which is a risk factor for ASCVD. Statins can significantly increase the DNA-binding activity of Nrf2 and induce the expression of its target genes, such as HO-1 and glutathione peroxidase) GPx, (thus protecting the cells against oxidative stress. Antioxidant and anti-inflammatory properties of statins, which are independent of their lipid-lowering effects, could be partly explained by the modulation of the Nrf2/HO-1 pathway.
Introduction
We describe the case of a female child with multiple sulfatase deficiency (MSD) who received intravenous (IV) trehalose (15 g/week) for 3 months.
Material and methods
The efficacy of ...trehalose was evaluated by comparing serum biomarkers, a quality-of-life questionnaire (HRQoL), and imaging (brain MRI and ultrasonography of liver and spleen) at weeks 0 (W0) and 12 (W12).
Results
The improvement in quality of life assessments along with a slight decrease in the spleen dimensions were observed after 3 month intervention.
Conclusions
Future research with a larger MSD population and a longer-term follow-up is warranted to determine whether trehalose can improve MSD patient health and clinical outcomes.
Trehalose is a naturally occurring disaccharide of 2 glucose molecules, which has been suggested as a potential therapeutic agent to reduce blood glucose and ameliorate diabetes-related complications ...in type 2 diabetes (T2D). This study aimed to determine the efficacy of medium-term trehalose treatment in patients with T2D.
A double-blind, randomized, placebo-controlled trial in 40 patients with T2D was undertaken; 20 ingested trehalose 3.3 g/day and 20 placebo (sucrose), for 3 months. Parameters of glycaemic indices, high-sensitivity C-reactive protein (CRP), mood status, and quality of life were measured.
CRP was significantly lower with trehalose treatment (-0.62 ±0.3 mg/l,
= 0.02); however, no differences in glycaemic indices of fasting blood glucose (FBG) (-7.1 ±10.7 mg/dl,
= 0.15), glycated hemoglobin (HbA
) (-0.1 ±0.4%,
= 0.73), insulin (0.73 ±0.8 μU/ml,
= 0.39), or insulin resistance (HOMA-IR) (0.19 ±0.33,
= 0.56) were seen between groups after 12 weeks. Depression and stress scores were lower with trehalose compared to the placebo group (
= 0.02 and
= 0.05, respectively), whilst the quality-of-life score was higher with trehalose compared to placebo (
= 0.03) at the end of study. Between-group differences in these indices did not reach statistical significance (-2.36 ±1.20, -2.21 ±1.39 and 3.00 ±1.76 for depression, stress, and quality-of-life score, respectively) (
> 0.05). The pro-oxidant antioxidant balance (PAB) did not differ between groups (-4.6 ±12.8,
= 0.72).
12 weeks of treatment with 3.3 g/day of oral trehalose significantly improves CRP as a marker of inflammation, with potential favourable effects on quality of life, depression, and stress levels, but overall glycaemic control and pro-oxidant-antioxidant balance were unaltered during this time frame.
Niemann-Pick disease (NPD) types A (NPA) and B (NPB) are caused by deficiency of the acid sphingomyelinase enzyme, which is encoded by the
gene, resulting in progressive pathogenic accumulation of ...lipids in tissues. Trehalose has been suggested as an autophagy inducer with therapeutic neuroprotective effects. We performed a single-arm, open-label pilot study to assess the potential efficacy of trehalose treatment in patients with NPA and NPB patients.
Five patients with NPD type A and B were enrolled in an open-label, single-arm clinical trial. Trehalose was administrated intravenously (IV) (15 g/week) for three months. The efficacy of trehalose in the management of clinical symptoms was evaluated in patients by assessing the quality of life, serum biomarkers, and high-resolution computed tomography (HRCT) of the lungs at the baseline and end of the interventional trial (day 0 and week 12).
The mean of TNO-AZL Preschool children Quality of Life (TAPQOL) scores increased in all patients after intervention at W12 compared to the baseline W0, although the difference was not statistically significant. The serum levels of lyso-SM-509 and lyso-SM were decreased in three and four patients out of five, respectively, compared with baseline. Elevated ALT and AST levels were decreased in all patients after 12 weeks of treatment; however, changes were not statistically significant. Pro-oxidant antioxidant balance (PAB) was also decreased and glutathione peroxidase (GPX) activity was increased in serum of patients at the end of the study. Imaging studies of spleen and lung HRCT showed improvement of symptoms in two patients.
Positive trends in health-related quality of life (HRQoL), serum biomarkers, and organomegaly were observed after 3 months of treatment with trehalose in patients with NPA and NPB. Although not statistically significant, due to the small number of patients enrolled, these results are encouraging and should be further explored.
•NETosis is a pathogenic player of atherosclerosis and several other diseases.•Statins regulate NETosis via lipid-independent pleiotropic mechanisms.•The beneficial effects of statins may depend on ...the modulation of NETosis.
NETosis has emerged as a new player in the pathogenesis of several diseases including atherosclerotic cardiovascular disease. There is accumulating evidence suggesting that NETosis is regulated by statins, thereby justifying an important lipid-independent pleiotropic action of statin drugs in reducing the risk of atherothrombosis as well as other pathologies.
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MicroRNAs (miRNA) are one class of the small regulatory RNAs that can impact the expression of numerous genes including incretin hormones and their G protein-coupled receptors. ...Incretin peptides, including GLP-1, GLP-2, and GIP, are released from the gastrointestinal tract and have an crucial role in the glucose hemostasis and pancreatic beta-cell function. These hormones and their analogs with a longer half-life, glucagon like peptide-1 receptor agonists (GLP1RA), modify the expression of miRNAs. Dipeptidyl peptidase IV (DPP-4) is an enzyme that degrades the incretin hormones and is inactivated by DPP-4 inhibitors, which are a class of compounds used in the management of type 2 diabetes. DPP-4 inhibitors may also increase or reduce the expression of miRNAs. In this review, we describe the possible interactions between miRNAs and incretin hormones and the relevance of such interactions to physiological processes and diseases.
Amyloidosis is a concept that implicates disorders and complications that are due to abnormal protein accumulation in different cells and tissues. Protein aggregation‐associated diseases are ...classified according to the type of aggregates and deposition sites, such as neurodegenerative disorders and type 2 diabetes mellitus. Polyphenolic phytochemicals such as curcumin and its derivatives have anti‐amyloid effects both in vitro and in animal models; however, the underlying mechanisms are not understood. In this review, we summarized possible mechanisms by which curcumin could interfere with self‐assembly processes and reduce amyloid aggregation in amyloidosis. Furthermore, we discuss clinical trials in which curcumin is used as a therapeutic agent for the treatment of diseases linking to protein aggregates.
•Incretin hormones include glucagon-like peptide (GLP)-1, GLP-2 and GIP.•Incretin hormones have immunomodulatory and anti-inflammatory effects.•GLP-1 receptor agonist therapy has direct therapeutic ...effects on immunomodulation.•These agents may have therapeutic utility in the treatment of autoimmune disease.
Incretin hormones, including glucagon-like peptide (GLP)-1, GLP-2 and glucose-dependent insulinotropic polypeptide (GIP), are gastrointestinal peptides secreted from enteroendocrine cells. These hormones play significant roles in many physiological processes via binding to G-protein coupled receptors (GPCRs) on different organs and tissues; one of them is the immunomodulatory effect on the immune system and its molecular components such as cytokines and chemokines. Anti-inflammatory effects of incretins and dependent molecules involving long-acting analogs and DPP4 inhibitors through regulation of T and B cell activation may attenuate autoimmune diseases caused by immune system disorders in mistakenly recognizing self as the foreign agent.
In this review, we investigate incretin effects on the immune system response and the potential benefits of incretin-based therapy for treating autoimmune diseases.
Statins are a class of cholesterol-lowering drugs that inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Anti-inflammatory and antioxidant properties, as well as improvement of ...endothelial function and plaque stabilization have also been proposed as parts of the pleiotropic effects of statins. Specialized pro-resolving mediators (SPMs) are endogenous lipid-derived molecules originating from ω-6 and ω-3 polyunsaturated fatty acids, such as arachidonic, docosahexaenoic and eicosapentaenoic acid that trigger and modulate the resolution of inflammation. Impaired SPM biosynthesis can lead to excessive or chronic inflammation and is implicated in the pathogenesis of several diseases. Exogenous administration of SPMs, including lipoxin, maresin, protectin, have been shown to improve both bacterial and viral infections, mainly in preclinical models, thus minimizing inflammation. Statin-triggered-SPM production in several in vitro and in vivo models may represent another anti-inflammatory pathway involving these drugs. This commentary discusses scientific publications on the effects of statins on SPMs and the resolution of inflammation process.
Statins can promote SPMs generation and thus subsequently enhance the resolution of inflammation in certain diseases, such as cardiovascular disease, sepsis, rheumatoid arthritis, bacterial and viral infections Display omitted
Oxidative stress that occurs as a consequence of the imbalance between antioxidant activity and free radicals can contribute in the pathogenesis of metabolic disorders, such as type 2 diabetes ...mellitus (T2DM). Antioxidant therapies have been proposed as possible approaches to treat and attenuate diabetic complications. The purpose of this study was to evaluate potential antioxidant effects of trehalose on oxidative indices in a streptozotocin (STZ)-induced diabetic rat model.
Diabetic rats were divided randomly into five treatment groups (six rats per group). One test group received 45 mg/kg/day trehalose via intraperitoneal injection, and another received 1.5 mg/kg/day trehalose via oral gavage for 4 weeks. Three control groups were also tested including nondiabetic rats as a normal control (NC), a nontreated diabetic control (DC), and a positive control given 200 mg/kg/day metformin. Levels of thiol groups (-SH), and serum total antioxidant capacity were measured between control and test groups. In addition, superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme activities were assessed.
In both oral and injection trehalose-treated groups, a marked increase was observed in serum total antioxidant capacity (TAC) (p > 0.05) and thiol groups (-SH) (p < 0.05). Also, SOD and GPx activities were increased after 4 weeks of treatment with trehalose.
In conclusion, the present results indicate ameliorative effects of trehalose on oxidative stress, with increase antioxidant enzyme activities in STZ-induced diabetic rats.
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