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Biochimica Et Biophysica Acta.... Nov 2023This study aims to explore the potential biomarkers in the development of diabetes mellitus (DM) into diabetic retinopathy (DR).
Integration of systematic review, lipidomics with experiment verification reveals abnormal sphingolipids facilitate diabetic retinopathy by inducing oxidative stress on RMECs.
OBJECTIVE
This study aims to explore the potential biomarkers in the development of diabetes mellitus (DM) into diabetic retinopathy (DR).
METHODS
Systematic review of diabetic metabolomics was used to screen the differential metabolites and related pathways during the development of DM. Non-targeted lipidomics of rat plasma was performed to explore the differential metabolites in the development of DM into DR in vivo. To verify the effects of differential metabolites in inducing retinal microvascular endothelial cells (RMECs) injury by increasing oxidative stress, high glucose medium containing differential metabolites was used to induce rat RMECs injury and cell viability, malondialdehyde (MDA) contents, superoxide dismutase (SOD) activities, reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) were evaluated in vitro. Network pharmacology was performed to explore the potential mechanism of differential metabolites in inducing DR.
RESULTS
Through the systematic review, 148 differential metabolites were obtained and the sphingolipid metabolic pathway attracted our attention. Plasma non-targeted lipidomics found that sphingolipids were accompanied by the development of DM into DR. In vitro experiments showed sphinganine and sphingosine-1-phosphate aggravated rat RMECs injury induced by high glucose, further increased MDA and ROS levels, and further decreased SOD activities and MMP. Network pharmacology revealed sphinganine and sphingosine-1-phosphate may induce DR by regulating the AGE-RAGE and HIF-1 signaling pathways.
CONCLUSIONS
Integrated systematic review, lipidomics and experiment verification reveal that abnormal sphingolipid metabolism facilitates DR by inducing oxidative stress on RMECs. Our study could provide the experimental basis for finding potential biomarkers for the diagnosis and treatment of DR.
Topics: Rats; Animals; Diabetic Retinopathy; Reactive Oxygen Species; Sphingolipids; Lipidomics; Endothelial Cells; Oxidative Stress; Glucose; Superoxide Dismutase; Biomarkers; Diabetes Mellitus
PubMed: 37659619
DOI: 10.1016/j.bbalip.2023.159382 -
Current Medicinal Chemistry Aug 2023The literature suggests that statins may increase superoxide dismutase (SOD) levels by different mechanisms. These effects may contribute to the antioxidant and...
BACKGROUND AND OBJECTIVE
The literature suggests that statins may increase superoxide dismutase (SOD) levels by different mechanisms. These effects may contribute to the antioxidant and anti-inflammatory effects of statins, which are thought to be beneficial in preventing cardiovascular events. However, there are also conflicting results concerning the effect of statins on SOD levels. The goal of this systematic review was to evaluate the effect of statin therapy on SOD activity.
METHODS
This systematic review was performed based on the PRISMA statement. The terms ("statin" or "HMG-CoA reductase inhibitor" OR "lipid-lowering agents" OR "Atorvastatin" OR "Simvastatin" OR "Pravastatin" OR "Fluvastatin" OR "Lovastatin") AND ("superoxide dismutase" OR "SOD" OR "anti-oxidative" OR "oxidative stress") were searched in database systems Google Scholar, PubMed/MEDLINE, and Scopus from inception to April 2022.
RESULTS
A total of 14 controlled clinical trials - 10 randomized and 4 non-randomized - were found to be eligible. Four studies measured SOD levels in plasma, six in serum, two in red blood cells, one in venous blood, and one on both red blood cells and venous blood matrices. Seven clinical trials used atorvastatin, six used simvastatin, and four used rosuvastatin. Six studies reported an increase in SOD activity, seven found no significant changes, and one showed a reduced SOD activity.
CONCLUSION
Our systematic review suggests that treatment with statins has a positive effect on SOD activity. However, evidence from further randomized controlled trials is required to confirm the potential antioxidant effect of statin therapy.
PubMed: 37653630
DOI: 10.2174/0929867331666230831145809 -
Antioxidants (Basel, Switzerland) Aug 2023Sleep deprivation is highly prevalent in the modern world, possibly reaching epidemic proportions. While multiple theories regarding the roles of sleep exist... (Review)
Review
Sleep deprivation is highly prevalent in the modern world, possibly reaching epidemic proportions. While multiple theories regarding the roles of sleep exist (inactivity, energy conservation, restoration, brain plasticity and antioxidant), multiple unknowns still remain regarding the proposed antioxidant roles of sleep. The existing experimental evidence is often contradicting, with studies pointing both toward and against the presence of oxidative stress after sleep deprivation. The main goals of this review were to analyze the existing experimental data regarding the relationship between sleep deprivation and oxidative stress, to attempt to further clarify multiple aspects surrounding this relationship and to identify current knowledge gaps. Systematic searches were conducted in three major online databases for experimental studies performed on rat models with oxidative stress measurements, published between 2015 and 2022. A total of 54 studies were included in the review. Most results seem to point to changes in oxidative stress parameters after sleep deprivation, further suggesting an antioxidant role of sleep. Alterations in these parameters were observed in both paradoxical and total sleep deprivation protocols and in multiple rat strains. Furthermore, the effects of sleep deprivation seem to extend beyond the central nervous system, affecting multiple other body sites in the periphery. Sleep recovery seems to be characterized by an increased variability, with the presence of both normalizations in some parameters and long-lasting changes after sleep deprivation. Surprisingly, most studies revealed the presence of a stress response following sleep deprivation. However, the origin and the impact of the stress response during sleep deprivation remain somewhat unclear. While a definitive exclusion of the influence of the sleep deprivation protocol on the stress response is not possible, the available data seem to suggest that the observed stress response may be determined by sleep deprivation itself as opposed to the experimental conditions. Due to this fact, the observed oxidative changes could be attributed directly to sleep deprivation.
PubMed: 37627596
DOI: 10.3390/antiox12081600 -
Frontiers in Pharmacology 2023Although several meta-analyses support the positive effect of coenzyme Q10 (CoQ10) on biomarkers of oxidative stress and inflammation, the results of some other studies...
Although several meta-analyses support the positive effect of coenzyme Q10 (CoQ10) on biomarkers of oxidative stress and inflammation, the results of some other studies reject such effects. Therefore, in this umbrella meta-analysis, we performed a comprehensive systematic search in such databases as Web of Science, PubMed, Scopus, Embase, and Google Scholar up to January 2023. Based on standardized mean difference analysis, CoQ10 supplementation significantly decreased serum C-reactive protein (CRP) (ES = -0.39; 95% CI: 0.77, -0.01, = 0.042) and malondialdehyde (MDA) (ES = -1.17; 95% CI: 1.55, -0.79, < 0.001), while it increased the total antioxidant capacity (TAC) (ES = 1.21; 95% CI: 0.61, 1.81, < 0.001) and serum superoxide dismutase (SOD) activity (ES = 1.08; 95% CI: 0.37, 1.79, = 0.003). However, CoQ10 supplementation had no significant reducing effect on tumor-necrosis factor-alpha (TNF- α) (ES = -0.70; 95% CI: 2.09, 0.68, = 0.320) and interleukin-6 (IL-6) levels (ES = -0.85; 95% CI: 1.71, 0.01, = 0.053). Based on weighted mean difference analysis, CoQ10 supplementation considerably decreased TNF-α (ES = -0.46, 95% CI: 0.65, -0.27; < 0.001), IL-6 (ES = -0.92, 95% CI: 1.40, -0.45; < 0.001), and CRP levels (effect sizes = -0.28, 95% CI: 0.47, -0.09; < 0.001). The results of our meta-analysis supported the alleviating effects of CoQ10 on markers of inflammation cautiously. However, CoQ10 had antioxidant effects regarding the improvement of all the studied antioxidant and oxidative stress biomarkers. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=323861, identifier CRD42022323861.
PubMed: 37614320
DOI: 10.3389/fphar.2023.1191290 -
Central Nervous System Agents in... 2023Depression and anxiety are the most common mental disorders worldwide.
BACKGROUND
Depression and anxiety are the most common mental disorders worldwide.
OBJECTIVE
We aimed to review silymarin and silibinin effects and underlying mechanisms in the central nervous system (CNS) for depression and anxiety treatment.
METHODS
The research protocol was prepared based on following the PRISMA statement. An extensive search was done in essential databases such as PubMed, Cochrane Library, Web of Science (ISI), Embase, and Scopus. Considering the study inclusion and exclusion criteria, 17 studies were finally included. The desired information was extracted from the studies and recorded in Excel, and the consequences and mechanisms were reviewed.
RESULTS
Silymarin and silibinin upregulated brain-derived neurotrophic factor (BDNF) and improved neural stem cells (NSCs) proliferation in the cortex and hippocampus. They also increased neurochemical serotonin (5-HT), dopamine (DA), and norepinephrine (NE) levels. Silymarin and silibinin reduced malondialdehyde (MDA) formation and increased glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities. In addition, silymarin and silibinin reduced interleukin (IL)-6, IL-1β, and IL-12β, reducing tumor necrosis factor α (TNF-α) induced neuroinflammation.
CONCLUSION
Silymarin and silibinin exert anti-depression and anxiolytic effects by regulating neurotransmitters, endocrine, neurogenesis, and immunologic systems. Therefore, as natural and complementary medicines, they can be used to reduce the symptoms of depression and anxiety; However, more clinical studies are needed in this field.
Topics: Humans; Silymarin; Silybin; Depression; Antioxidants; Anxiety Disorders; Hippocampus; Glutathione
PubMed: 37612866
DOI: 10.2174/1871524923666230823094403 -
Nutrients Jul 2023Stevia ( Bertoni) is an aromatic plant known for its high sweetening power ascribed to its glycosides. Stevia also contains several bioactive compounds showing... (Meta-Analysis)
Meta-Analysis Review
Stevia ( Bertoni) is an aromatic plant known for its high sweetening power ascribed to its glycosides. Stevia also contains several bioactive compounds showing antioxidant, antiproliferative, antimicrobial, and anti-inflammatory activities. Since inflammation and oxidative stress play critical roles in the pathogenesis of many diseases, stevia emerges as a promising natural product that could support human health. In this study we set out to investigate the way stevia affects oxidative stress markers (e.g., SOD, CAT, GPx, GSH, MDA) in diseased rats administered stevia leaf extracts or glycosides. To this end, we performed an inclusive literature search, following PRISMA guidelines, and recruited multivariate meta-analysis and meta-regression to synthesize all available data on experimental animal models encountering (a) healthy, (b) diseased, and (c) stevia-treated diseased rats. From the 184 articles initially retrieved, 24 satisfied the eligibility criteria, containing 104 studies. Our results demonstrate that regardless of the assay employed, stevia leaf extracts restored all oxidative stress markers to a higher extent compared to pure glycosides. Meta-regression analysis revealed that results from SOD, CAT, GSH, and TAC assays are not statistically significantly different ( = 0.184) and can be combined in meta-analysis. Organic extracts from stevia leaves showed more robust antioxidant properties compared to aqueous or hydroalcoholic ones. The restoration of oxidative markers ranged from 65% to 85% and was exhibited in all tested tissues. Rats with diabetes mellitus were found to have the highest restorative response to stevia leaf extract administration. Our results suggest that stevia leaf extract can act protectively against various diseases through its antioxidant properties. However, which of each of the multitude of stevia compounds contribute to this effect, and to what extent, awaits further investigation.
Topics: Humans; Rats; Animals; Antioxidants; Stevia; Plant Extracts; Glycosides; Superoxide Dismutase; Plant Leaves
PubMed: 37571265
DOI: 10.3390/nu15153325 -
Food & Function Aug 2023The fruit of Linn., which mainly grows in tropical and subtropical regions, is well-known for its medicine and food homology properties. It has a distinctive flavor,... (Review)
Review
The fruit of Linn., which mainly grows in tropical and subtropical regions, is well-known for its medicine and food homology properties. It has a distinctive flavor, great nutritional content, and potent antioxidant, anti-inflammatory, anti-cancer and immunoregulatory effects. According to an increasing amount of scientific and clinical evidence, this fruit shows significant potential for application and development in the field of oral health management. Through the supplementation of vitamins, superoxide dismutase (SOD) and other nutrients reduce virulence expression of various oral pathogens, prevent tissue and mucosal damage caused by oxidative stress, . fruit can promote saliva secretion, regulate the balance of the oral microecology, prevent and treat oral cancer early, promote alveolar bone remodeling and aid mucosal wound healing. Thus, it plays a specific role in the prevention and treatment of common oral disorders, producing surprising results. For instance, enhancing the effectiveness of scaling and root planing in the treatment of periodontitis, relieving mucosal inflammation caused by radiotherapy for oral cancer, and regulating the blood glucose metabolism to alleviate oral discomfort. Herein, we systematically review the latest research on the use of fruit in the management of oral health and examine the challenges and future research directions based on its chemical composition and characteristics.
Topics: Humans; Fruit; Phyllanthus emblica; Plant Extracts; Polyphenols; Mouth Neoplasms
PubMed: 37529983
DOI: 10.1039/d3fo01671d -
Antioxidants (Basel, Switzerland) Jul 2023Epilepsy is a neurological disorder characterized by epileptic seizures resulting from neuronal hyperexcitability, which may be related to failures in Na,K-ATPase... (Review)
Review
Antioxidant Therapy Reduces Oxidative Stress, Restores Na,K-ATPase Function and Induces Neuroprotection in Rodent Models of Seizure and Epilepsy: A Systematic Review and Meta-Analysis.
Epilepsy is a neurological disorder characterized by epileptic seizures resulting from neuronal hyperexcitability, which may be related to failures in Na,K-ATPase activity and oxidative stress participation. We conducted this study to investigate the impact of antioxidant therapy on oxidative stress, Na,K-ATPase activity, seizure factors, and mortality in rodent seizure/epilepsy models induced by pentylenetetrazol (PTZ), pilocarpine (PILO), and kainic acid (KA). After screening 561 records in the MEDLINE, EMBASE, Web of Science, Science Direct, and Scopus databases, 22 were included in the systematic review following the PRISMA guidelines. The meta-analysis included 14 studies and showed that in epileptic animals there was an increase in the oxidizing agents nitric oxide (NO) and malondialdehyde (MDA), with a reduction in endogenous antioxidants reduced glutathione (GSH) and superoxide dismutase (SO). The Na,K-ATPase activity was reduced in all areas evaluated. Antioxidant therapy reversed all of these parameters altered by seizure or epilepsy induction. In addition, there was a percentage decrease in the number of seizures and mortality, and a meta-analysis showed a longer seizure latency in animals using antioxidant therapy. Thus, this study suggests that the use of antioxidants promotes neuroprotective effects and mitigates the effects of epilepsy. The protocol was registered in the Prospective Register of Systematic Reviews (PROSPERO) CRD42022356960.
PubMed: 37507936
DOI: 10.3390/antiox12071397 -
Frontiers in Pharmacology 2023Diabetic nephropathy (DN) is the main cause of chronic kidney disease (CKD) and end-stage renal failure (ESRF), and the control of disease progression and adverse...
Diabetic nephropathy (DN) is the main cause of chronic kidney disease (CKD) and end-stage renal failure (ESRF), and the control of disease progression and adverse events during treatment needs to be improved. This study aimed to systematically evaluate the clinical efficacy and safety of Niaoduqing granules (NDQG) in the treatment of diabetic kidney disease (DKD). Randomized controlled trials (RCTs) of NDQG for DKD from Chinese and English databases up to 31 August 2022 were included. The quality of the literature was assessed using the risk of bias tool of the Cochrane Handbook. At a 95% confidence interval (CI), relative risk (RR) and Cohen's d were used for the categorical and continuous variables, respectively, and Stata 16.0 software was used for statistical analysis. A funnel plot and Egger's tests were used to assess publication bias. A total of 4,006 patients were included in 52 RCTs, including 1,987 cases in the control group and 2,019 cases in the treatment group. Compared with conventional treatment (CT), combined NDQG therapy is more effective in improving clinical efficiency [RR = 1.23, 95% confidence interval (1.17, 1.29), < 0.001, = 53.17%], kidney function (urinary albumin excretion rate [SMD = -0.90, 95% CI (-1.14, -0.66), < 0.001, = 78.19%], 24hUTP levels [SMD = -0.81, 95% CI (-1.08, -0.55), < 0.001, = 87.08%], blood urea nitrogen [SMD = -0.54, 95% CI (-0.69, -0.39), < 0.01, = 77.01%], SCr [SMD = -0.68, 95% CI (-0.90, -0.45), < 0.001, = 89.97%], CCr [SMD = 0.76, 95% CI (0.10,1.42), = 0.02, = 95.97%], and Cys-C [SMD = -1.32, 95% CI (-2.25, -0.40), = 0.01, = 93.44%]), the level of glucose metabolism (fasting blood glucose [SMD = -0.18, 95% CI (-0.38, 0.03), = 0.10, = 71.18%] and HbA1c [SMD = -0.42, 95% CI (-0.86, -0.02), = 0.06, = 81.64%]), the level of lipid metabolism (total cholesterol [SMD = -0.70, 95% CI (-1.01, -0.39), < 0.001, = 86.74%] and triglyceride [SMD = -0.61, 95% CI (-0.87,-0.36), < 0.001, = 80.64%]), inflammatory factors (Hs-CRP [SMD = -1.00, 95% CI (-1.54, -0.46), < 0.001, = 86.81%], IL-18 [SMD = -1.25, 95% CI (-1.58, -0.92), < 0.001, = 0], and TNF-α [SMD = -1.28, 95% CI (-1.64, -0.91), < 0.001, = 75.73%]), and indicators of oxidative stress (malondialdehyde [SMD = -0.88, 95% CI (-1.22, -0.54), < 0.001, = 66.01%] and advanced oxidation protein products [SMD = -0.92, 95% CI (-1.85, 0.00), < 0.001, = 90.68%]). In terms of improving uric acid [SMD = -1.59, 95% CI (-3.45, 0.27), = 0.09, = 94.67%], 2hPG [SMD = -0.04, 95% CI (-0.61, 0.53), = 0.89, = 84.33%], HDL-C [SMD = 0.71, 95% CI (0.02, 1.40), = 0.04, = 87.43%], Hb [SMD = 0.11, 95% CI (-0.10, 0.32), = 0.32, = 0.00]), and superoxide dismutase [SMD = 1.32, 95% CI (0.44, 2.20), < 0.001, = 93.48%], the effect is not obvious. Adjuvant treatment with NDQG did not increase the incidence of adverse reactions in the control group [SMD = 0.98, 95% CI (0.71, 1.34), = 0.89, = 1.59%]. Obvious publication bias was detected by funnel plot and Egger's test. Our meta-analysis showed that adjuvant treatment with NDQG has more advantages than conventional treatment alone in the DKD treatment, which could improve clinical efficiency, kidney function, the level of glucose metabolism, the level of lipid metabolism, inflammatory factors, and oxidative stress indicators. At the same time, it also showed that NDQG are relatively safe. However, more high-quality studies are needed to provide more reliable evidence for clinical use. : https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022373726, identifier CRD42022373726.
PubMed: 37475716
DOI: 10.3389/fphar.2023.1180751 -
Phytotherapy Research : PTR Sep 2023To determine the pharmaceutical applications, we assessed the evidence from preclinical studies about the hypoglycemic, hypolipidemic, and antioxidant potential of... (Meta-Analysis)
Meta-Analysis Review
To determine the pharmaceutical applications, we assessed the evidence from preclinical studies about the hypoglycemic, hypolipidemic, and antioxidant potential of Pistacia atlantica (PA) as a natural source for prevention and treatment of diabetes. A comprehensive literature search of the articles published until March 12, 2022 was conducted on PubMed, Embase, Web of Sciences, and Scopus databases, using relevant keywords. This meta-analysis included 12 articles that examined the blood glucose (BG), insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), malondialdehyde (MDA) and superoxide dismutase (SOD). A random-effects model was used to estimate the pooled effect size. Findings indicated that PA supplementation significantly decreased BG, HOMA-IR, TC, TG, and MDA, and increased insulin and SOD in diabetic animals compared with control group (p < .05). However, PA supplementation had no significant effects on HDL-C (p > .05). The subgroup analysis also confirmed the beneficial effect of PA supplementation with longer duration (>4 weeks) and higher doses (≥100 mg/kg/day) as well as in the extract type. The studies have heterogeneity associated with methodological diversity and there were some concerns about the risk of bias, especially about randomization and blind outcome assessment. This meta-analysis provided convincing evidence for antidiabetic, hypolipidemic, and antioxidant activity of PA in animals. Further high-quality studies are needed to firmly establish the clinical efficacy of the plant.
Topics: Animals; Antioxidants; Hypoglycemic Agents; Pistacia; Plant Extracts; Diabetes Mellitus; Blood Glucose; Insulin; Insulin Resistance; Superoxide Dismutase; Triglycerides; Cholesterol
PubMed: 37428094
DOI: 10.1002/ptr.7898