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Phytomedicine : International Journal... Oct 2023Several clinical and experimental studies have shown that therapeutic strategies targeting oxidative damage are beneficial for subarachnoid hemorrhage (SAH). A...
BACKGROUND
Several clinical and experimental studies have shown that therapeutic strategies targeting oxidative damage are beneficial for subarachnoid hemorrhage (SAH). A brain-permeable flavonoid, dihydromyricetin (DHM), can modulate redox/oxidative stress and has cerebroprotective effects in several neurological disorders. The effects of DHM on post-SAH early brain injury (EBI) and the underlying mechanism have yet to be clarified.
PURPOSE
This work investigated a potential role for DHM in SAH, together with the underlying mechanisms.
METHODS
Cerebroprotection by DHM was studied using a SAH rat model and primary cortical neurons. Atorvastatin (Ato) was a positive control drug in this investigation. The effects of DHM on behavior after SAH were evaluated by performing the neurological rotarod and Morris water maze tests, as well as by examining its effects on brain morphology and on the molecular and functional phenotypes of primary cortical neurons using dichlorodihydrofluorescein diacetate (DCFH-DA), immunofluorescent staining, biochemical analysis, and Western blot.
RESULTS
DHM was found to significantly reduce the amount of reactive oxygen species (ROS), suppress mitochondrial disruption, and increase intrinsic antioxidant enzymatic activity following SAH. DHM also significantly reduced neuronal apoptosis in SAH rats and improved short- and long-term neurological functions. DHM induced significant increases in peroxiredoxin 2 (Prx2) and nuclear factor erythroid 2-related factor 2 (Nrf2) expression, while decreasing phosphorylation of p38 and apoptotic signal-regulated kinase 1 (ASK1). In contrast, reduction of Prx2 expression using small interfering ribonucleic acid or by inhibiting Nrf2 with ML385 attenuated the neuroprotective effect of DHM against SAH. Moreover, DHM dose-dependently inhibited oxidative damage, decreased neuronal apoptosis, and increased the viability of primary cultured neurons in vitro. These positive effects were associated with Nrf2 activation and stimulation of Prx2 signaling, whereas ML385 attenuated the beneficial effects.
CONCLUSION
These results reveal that DHM protects against SAH primarily by modulating the Prx2 signaling cascade through the Nrf2-dependent pathway. Hence, DHM could be a valuable therapeutic candidate for SAH treatment.
Topics: Signal Transduction; Subarachnoid Hemorrhage; Cytoprotection; Male; Animals; Rats; Rats, Sprague-Dawley; Cells, Cultured; Oxidative Stress; Cell Survival
PubMed: 37523836
DOI: 10.1016/j.phymed.2023.154997 -
Free Radical Biology & Medicine Nov 2023A novel circRNA named circSQSTM1 (hsa_circRNA_075320) was screened out in atorvastatin (ATV) stimulated endothelial cells (ECs) by our group. Considering the...
A novel circRNA named circSQSTM1 (hsa_circRNA_075320) was screened out in atorvastatin (ATV) stimulated endothelial cells (ECs) by our group. Considering the anti-atherosclerotic function of ATV, we hypothesized the circSQSTM1 could protect ECs functions in AS progression. The effects of circSQSTM1 on ECs inflammation, oxidative stress and autophagy were measured by qRT-PCR, Western blotting, monocyte-endothelial adhesion assay, dichloro-dihydro-fluorescein diacetate and mCherry-GFP-LC3 labeling. A luciferase reporter assay, RNA immunoprecipitation, MS2-tagging system and fluorescence in situ hybridization were performed to identify the biological functions of circSQSTM1. The partial left carotid artery ligation model and atherosclerosis model were established to analyze the effects of circSQSTM1 on atherosclerosis progression in vivo. Our results revealed that ATV induced the accumulation of circSQSTM1 in ECs via suppressing m6A modified degradation. In the cytoplasm, circSQSTM1 could relieve Sirt1 by competitively sponging miR-23b-3p. In the nucleus, circSQSTM1 directly interacts with eIF4A3 and promoting the efficient nuclear export of FOXO1 mRNA, which encodes FOXO1 transcription factor to directly activate Sirt1 promoter activity. Hence, circSQSTM1 reduced inflammation, inhibited oxidative stress and promoted autophagy by upregulating Sirt1 in ECs. Moreover, circSQSTM1 overexpression in ECs attenuated the progression of atherosclerosis in ApoE mice. Taken together, the unique noncoding RNA known as circSQSTM1 took a protective role to the ECs in atherosclerosis.
Topics: Animals; Mice; Atherosclerosis; Endothelial Cells; In Situ Hybridization, Fluorescence; Inflammation; RNA, Circular; Sirtuin 1; Atorvastatin
PubMed: 37865306
DOI: 10.1016/j.freeradbiomed.2023.10.398 -
World Neurosurgery: X Jul 2023Despite recent encouraging pharmaceutical and technical breakthroughs in neurosurgical critical care, traumatic brain injury (TBI)-related mortality and morbidity remain... (Review)
Review
Despite recent encouraging pharmaceutical and technical breakthroughs in neurosurgical critical care, traumatic brain injury (TBI)-related mortality and morbidity remain substantial clinical issues. Medication of statins was revealed to enhance outcomes following TBI in animal research. In addition to their main role of decreasing serum cholesterol, statins decrease inflammation and enhance cerebral blood flow. However, research on the efficacy of statins in TBI is still limited. This systematic review was conducted to determine the efficacy of statins in enhancing the clinical outcomes of TBI individuals, and specifically investigate the optimal dose and form of statins. The databases of PubMed, DOAJ, EBSCO, and Cochrane were extensively researched. The date of publication within the last fifteen years was the inclusion criterion. Meta-analyses, clinical trials, and randomized controlled trials were prioritized forms of research publications. Ambiguous remarks, irrelevant correlations to the main issue, or a focus on disorders other than TBI were the exclusion criteria. Thirteen research were included in this study. Simvastatin, atorvastatin, and rosuvastatin were the main form of statins discussed in this study. Enhancement of the Glasgow Coma Scale, survival rates, hospital length of stay, and cognitive outcomes were revealed in this study. This study suggests either simvastatin 40 mg, atorvastatin 20 mg, or rosuvastatin 20 mg for 10 days as the optimal therapeutic forms and doses to be applied in the management of TBI. Pre-TBI statin use was linked to lower risk of mortality in TBI individuals compared to nonusers, whereas statin discontinuation was linked to an increase in mortality.
PubMed: 37251243
DOI: 10.1016/j.wnsx.2023.100211 -
Cureus Dec 2023The aim of this study was to assess and compare the efficacy of atorvastatin with rosuvastatin in preventing cardiovascular events among patients already diagnosed with... (Review)
Review
The aim of this study was to assess and compare the efficacy of atorvastatin with rosuvastatin in preventing cardiovascular events among patients already diagnosed with cardiovascular disease (CVD). We performed this systematic review and meta-analysis as per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Two investigators independently searched online databases, including PubMed, the Cochrane Library, and the Excerpta Medica database (Embase), from the inception of databases until November 2023. The primary outcome assessed in the meta-analysis included cardiovascular mortality and a composite of cardiovascular events. Other outcomes included myocardial infarction and stroke. A total of four studies were selected for our meta-analysis. A total of 7,378 patients were enrolled, including 3,721 in the atorvastatin group and 3,657 in the rosuvastatin group. Pooled analysis showed that the incidence of composite cardiovascular events was not significantly different in patients receiving atorvastatin and patients receiving rosuvastatin (risk ratio (RR): 0.93, 95% confidence interval (CI): 0.79 to 1.09, p-value: 0.38, I-square: 0%). Pooled analysis showed that the risk of cardiovascular mortality was not significantly different between the two study groups (RR: 0.96, 95% CI: 0.51 to 1.81, p-value: 0.93, I-square: 0%). In conclusion, our meta-analysis, based on four selected studies, found no significant disparities in composite cardiovascular events, cardiovascular mortality, myocardial infarction, or stroke between patients administered atorvastatin and those receiving rosuvastatin. This outcome underscores the comparable efficacy of these statins in mitigating cardiovascular risks, highlighting their clinical equipoise in the realm of secondary prevention.
PubMed: 38222118
DOI: 10.7759/cureus.50421 -
Medicine May 2024Statins are the first-line treatment for dyslipidemia, which is a major modifiable risk factor for atherosclerotic cardiovascular disease. Studies have shown that in... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
Statins are the first-line treatment for dyslipidemia, which is a major modifiable risk factor for atherosclerotic cardiovascular disease. Studies have shown that in addition to the beneficial lipid-lowering effect, statins also exhibit a number of pleiotropic effects that may find application in other diseases, including osteoporosis. This study aimed to assess the effect of statins on bone turnover, as measured by the concentration of bone turnover markers, and to compare the effect of atorvastatin as a lipophilic statin and rosuvastatin as a hydrophilic statin.
METHODS
This study included 34 postmenopausal women aged < 65 years with newly diagnosed dyslipidemia requiring statin therapy. Patients were randomly assigned to receive a statin drug. Statins were initiated at standard doses of 5 to 10 mg of rosuvastatin and 20 mg of atorvastatin. The levels of C-terminal telopeptide of type I collagen as a bone resorption marker and N-terminal propeptide of procollagen type I as a marker of bone formation, lipid concentrations and other biochemical parameters were assessed at baseline and after 6 and twelve months of treatment.
RESULTS
There were no statistically significant differences between the levels of bone turnover markers before and 6 months after statin implementation (P > .05) - for all patients or subgroups according to statin use. Analysis of the results showed that after 12 months, there was a statistically significant decrease in N-terminal propeptide of procollagen type I concentration in all subjects (P = .004). By statin subgroup, a statistically significant decrease in N-terminal propeptide of procollagen type I was observed only in patients receiving rosuvastatin (P = .012) and not in those receiving atorvastatin (P = .25). Moreover, changes in bone turnover markers did not correlate with changes in lipid concentrations.
CONCLUSIONS
These results may indicate the superiority of atorvastatin over rosuvastatin in inhibiting adverse changes in bone turnover in postmenopausal women. Confirmed by studies involving a larger population, the observed differences might find particular applications in clinical practice, and the choice of atorvastatin over rosuvastatin for women could be considered in the early postmenopausal period to reduce the risk of osteoporosis and subsequent osteoporotic fractures.
Topics: Humans; Rosuvastatin Calcium; Female; Atorvastatin; Middle Aged; Bone Remodeling; Postmenopause; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Biomarkers; Collagen Type I; Osteoporosis, Postmenopausal; Dyslipidemias
PubMed: 38728464
DOI: 10.1097/MD.0000000000038122 -
BMC Complementary Medicine and Therapies Nov 2023Cardiovascular disease and cancer are the main causes of morbidity and mortality worldwide. Studies have shown that these two diseases may have some common risk factors....
BACKGROUND
Cardiovascular disease and cancer are the main causes of morbidity and mortality worldwide. Studies have shown that these two diseases may have some common risk factors. Atorvastatin is mainly used for the treatment of atherosclerosis in clinic. A large number of studies show that atorvastatin may produce anti-tumor activities. This study aimed to predict the common targets of atorvastatin against atherosclerosis and non-small cell lung cancer (NSCLC) based on network pharmacology.
METHODS
The target genes of atherosclerosis and NSCLC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The disease-target-component model map and the core network were obtained using Cytoscape 3.7.1. The MTS and wound healing assay were used to detect the effect of atorvastatin on cell viability and migration of A549 cells. The expression of potential common target genes of atorvastatin against atherosclerosis and NSCLC were confirmed in A549 cells and lung cancer tissues of patients.
RESULTS
We identified 15 identical pathogenic genes, and four of which (MMP9, MMP12, CD36, and FABP4) were considered as the key target genes of atorvastatin in anti-atherosclerosis and NSCLC. The MTS and wound healing assays revealed that atorvastatin decreased A549 cells migration significantly. Atorvastatin markedly decreased the expression of MMP9, MMP12, CD36, and FABP4 in A549 cells and patients were treated with atorvastatin.
CONCLUSIONS
This study demonstrated 15 common pathogenic genes in both atherosclerosis and NSCLC. And verified that MMP 9, MMP 12, CD 36 and FABP 4 might be the common target genes of atorvastatin in anti-atherosclerosis and NSCLC.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Matrix Metalloproteinase 9; Atorvastatin; Matrix Metalloproteinase 12
PubMed: 37978381
DOI: 10.1186/s12906-023-04255-7 -
Revista Medica Del Instituto Mexicano... Oct 2023Atorvastatin has been used in the management of dyslipidemia and little is known about the efficacy and safety of high-dose atorvastatin administration for secondary... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Atorvastatin has been used in the management of dyslipidemia and little is known about the efficacy and safety of high-dose atorvastatin administration for secondary prevention of Major Cardiovascular Events (MACE).
OBJECTIVE
To evaluate the impact of high-dose atorvastatin on secondary prevention of MACE and adverse events.
MATERIAL AND METHODS
A systematic review and meta-analysis of Pubmed, Embase, Bireme and Cochrane Library Plus databases was performed, with a time scope from 1990 to July 2022. Six randomized clinical trials were included with a total of 29,333 patients who were treated with 80 mg, 10 mg or placebo doses of Atorvastatin where the main outcomes evaluated were Major Cardiovascular Events (MACE), mortality and treatment safety.
RESULTS
In the comparative study between the use of Atorvastatin 80 mg and other therapies, a relative risk (RR) of 0.8 (95%CI 0.69-0.92) was found, representing a 20% reduction in risk (RRR) and a number needed to treat (NNT) of 30-55. In the analysis of adverse effects, an RR of 2.37 (95% CI 0.86-6.53) and a number needed to harm (NNH) of 14-19 were observed. The use of 80 mg atorvastatin is associated with similar adverse events at lower doses.
CONCLUSIONS
The use of atorvastatin 80 mg is effective in the secondary prevention of Major Cardiovascular Event (MACE). The drug has adverse events that should be taken into account in secondary prevention.
Topics: Humans; Atorvastatin; Cardiovascular Diseases
PubMed: 37934798
DOI: 10.5281/zenodo.8319748 -
Communications Biology Mar 2024Regulating metabolic disorders has become a promising focus in treating intervertebral disc degeneration (IDD). A few drugs regulating metabolism, such as atorvastatin,...
Regulating metabolic disorders has become a promising focus in treating intervertebral disc degeneration (IDD). A few drugs regulating metabolism, such as atorvastatin, metformin, and melatonin, show positive effects in treating IDD. Glutamine participates in multiple metabolic processes, including glutaminolysis and glycolysis; however, its impact on IDD is unclear. The current study reveals that glutamine levels are decreased in severely degenerated human nucleus pulposus (NP) tissues and aging Sprague-Dawley (SD) rat nucleus pulposus tissues, while lactate accumulation and lactylation are increased. Supplementary glutamine suppresses glycolysis and reduces lactate production, which downregulates adenosine-5'-monophosphate-activated protein kinase α (AMPKα) lactylation and upregulates AMPKα phosphorylation. Moreover, glutamine treatment reduces NP cell senescence and enhances autophagy and matrix synthesis via inhibition of glycolysis and AMPK lactylation, and glycolysis inhibition suppresses lactylation. Our results indicate that glutamine could prevent IDD by glycolysis inhibition-decreased AMPKα lactylation, which promotes autophagy and suppresses NP cell senescence.
Topics: Rats; Animals; Humans; Intervertebral Disc Degeneration; Rats, Sprague-Dawley; Glutamine; AMP-Activated Protein Kinases; Autophagy; Lactates
PubMed: 38486093
DOI: 10.1038/s42003-024-06000-3 -
Life Sciences Jun 2024Atorvastatin is a commonly used cholesterol-lowering drug that possesses non-canonical anti-inflammatory properties. However, the precise mechanism underlying its...
AIMS
Atorvastatin is a commonly used cholesterol-lowering drug that possesses non-canonical anti-inflammatory properties. However, the precise mechanism underlying its anti-inflammatory effects remains unclear.
MATERIALS AND METHODS
The acute phase of ulcerative colitis (UC) was induced using a 5 % dextran sulfate sodium (DSS) solution for 7 consecutive days and administrated with atorvastatin (10 mg/kg) from day 3 to day 7. mRNA-seq, histological pathology, and inflammatory response were determined. Intestinal microbiota alteration, tryptophan, and its metabolites were analyzed through 16S rRNA sequencing and untargeted metabolomics.
KEY FINDINGS
Atorvastatin relieved the DSS-induced UC in mice, as evidenced by colon length, body weight, disease activity index score and pathological staining. Atorvastatin treatment reduced the level of pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Atorvastatin also relieved the intestinal microbiota disorder caused by UC and decreased the proliferation of pernicious microbiota such as Akkermansia and Bacteroides. Atorvastatin dramatically altered tryptophan metabolism and increased the fecal contents of tryptophan, indolelactic acid (ILA), and indole-3-acetic acid (IAA). Furthermore, atorvastatin enhanced the expression level of aryl hydrocarbon receptor (AhR) and interleukin-22 (IL-22) and further promoted the expression level of intestinal tight junction proteins, such as ZO-1 and occludin, in colitis mice.
SIGNIFICANCE
These findings indicated that atorvastatin could alleviate UC by regulating intestinal flora disorders, promoting microbial tryptophan metabolism, and repairing the intestinal barrier.
PubMed: 38852795
DOI: 10.1016/j.lfs.2024.122790 -
Medicine May 2024Hyperlipidemia is a common feature of chronic diseases. The aim of this work was designed to assess the role of probiotics (Lactobacillus casei Zhang, Bifidobactetium... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Hyperlipidemia is a common feature of chronic diseases. The aim of this work was designed to assess the role of probiotics (Lactobacillus casei Zhang, Bifidobactetium animalis subsp. lactis V9, and Lactobacillus plantarum P-8) in the treatment of hyperlipidemia.
METHODS
Thirty three patients with hyperlipidemia were randomly divided into a probiotic group (n = 18) and a control group (n = 15). The probiotic group was administered probiotics (2 g once daily) and atorvastatin 20 mg (once daily), and the control group was administered a placebo (2 g once daily) and atorvastatin 20 mg (once daily). Serum and fecal samples were gathered for subsequent analyses.
RESULTS
Time had a significant effect on the total cholesterol (TC), triglycerides (TG), and low-density lipoprotein-cholesterol (LDL-C) levels in the probiotic and control groups (P < .05). The gut microbial abundance in the probiotic group was markedly higher than that in the control group following 3-month probiotic treatment (P < .05). At the phylum level, probiotics exerted no notable effects on the relative abundance of Firmicutes, Bacteroidetes, and Actinobacteria but elevated that of Tenericutes and reduced Proteobacteria. At the genus level, probiotics increased the relative abundance of Bifidobacterium, Lactobacillus, and Akkermansia, and decreased that of Escherichia, Eggerthella, and Sutterella relative to the control group in months 1, 2, and 3 (P < .05).
CONCLUSIONS
Probiotics optimize the gut microbiota structure and decrease the amount of harmful bacteria in patients with hyperlipidemia. Probiotics can influence the composition of gut microorganisms and increase their diversity and abundance in vivo. It is recommended to use probiotics combined with atorvastatin to treat patients with hyperlipidemia.
Topics: Humans; Atorvastatin; Probiotics; Hyperlipidemias; Double-Blind Method; Male; Female; Middle Aged; Gastrointestinal Microbiome; Adult; Treatment Outcome; Triglycerides; Cholesterol, LDL; Anticholesteremic Agents; Lactobacillus plantarum; Feces; Aged; Combined Modality Therapy
PubMed: 38788020
DOI: 10.1097/MD.0000000000037883