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Basic & Clinical Pharmacology &... Jul 2024Parkinson's disease (PD) is a neurodegenerative disease that affects dopaminergic neurons, thus impairing dopaminergic signalling. Quercetin (QUE) has antioxidant and...
Parkinson's disease (PD) is a neurodegenerative disease that affects dopaminergic neurons, thus impairing dopaminergic signalling. Quercetin (QUE) has antioxidant and neuroprotective properties that are promising for the treatment of PD. This systematic review aimed to investigate the therapeutic effects of QUE against PD in preclinical models. The systematic search was performed in PubMed, Scopus and Web of Science. At the final screening stage, 26 articles were selected according to pre-established criteria. Selected studies used different methods for PD induction, as well as animal models. Most studies used rats (73.08%) and mice (23.08%), with 6-OHDA as the main strategy for PD induction (38.6%), followed by rotenone (30.8%). QUE was tested immersed in oil, nanosystems or in free formulations, in varied routes of administration and doses, ranging from 10 to 400 mg/kg and from 5 to 200 mg/kg in oral and intraperitoneal administrations, respectively. Overall, evidence from published data suggests a potential use of QUE as a treatment for PD, mainly through the inhibition of oxidative stress, neuroinflammatory response and apoptotic pathways.
Topics: Animals; Humans; Mice; Rats; Antioxidants; Apoptosis; Disease Models, Animal; Neuroprotective Agents; Oxidative Stress; Oxidopamine; Parkinson Disease; Parkinsonian Disorders; Quercetin; Rotenone
PubMed: 38682342
DOI: 10.1111/bcpt.14011 -
Nutrients Apr 2024Alcoholic Fatty Liver Disease (AFLD) is characterized by the accumulation of lipids in liver cells owing to the metabolism of ethanol. This process leads to a decrease... (Meta-Analysis)
Meta-Analysis
Alcoholic Fatty Liver Disease (AFLD) is characterized by the accumulation of lipids in liver cells owing to the metabolism of ethanol. This process leads to a decrease in the NAD/NADH ratio and the generation of reactive oxygen species. A systematic review and meta-analysis were conducted to investigate the role of oxidative stress in AFLD. A total of 201 eligible manuscripts were included, which revealed that animals with AFLD exhibited elevated expression of CYP2E1, decreased enzymatic activity of antioxidant enzymes, and reduced levels of the transcription factor Nrf2, which plays a pivotal role in the synthesis of antioxidant enzymes. Furthermore, animals with AFLD exhibited increased levels of lipid peroxidation markers and carbonylated proteins, collectively contributing to a weakened antioxidant defense and increased oxidative damage. The liver damage in AFLD was supported by significantly higher activity of alanine and aspartate aminotransferase enzymes. Moreover, animals with AFLD had increased levels of triacylglycerol in the serum and liver, likely due to reduced fatty acid metabolism caused by decreased PPAR-α expression, which is responsible for fatty acid oxidation, and increased expression of SREBP-1c, which is involved in fatty acid synthesis. With regard to inflammation, animals with AFLD exhibited elevated levels of pro-inflammatory cytokines, including TNF-a, IL-1β, and IL-6. The heightened oxidative stress, along with inflammation, led to an upregulation of cell death markers, such as caspase-3, and an increased Bax/Bcl-2 ratio. Overall, the findings of the review and meta-analysis indicate that ethanol metabolism reduces important markers of antioxidant defense while increasing inflammatory and apoptotic markers, thereby contributing to the development of AFLD.
Topics: Animals; Humans; Antioxidants; Cytochrome P-450 CYP2E1; Cytokines; Disease Models, Animal; Fatty Liver, Alcoholic; Lipid Peroxidation; Liver; NF-E2-Related Factor 2; Oxidative Stress; Reactive Oxygen Species
PubMed: 38674865
DOI: 10.3390/nu16081174 -
Antioxidants (Basel, Switzerland) Mar 2024The aging of the global population has increased the prevalence of neurodegenerative conditions. (BM), an herb with active compounds, such as bacosides A and B,... (Review)
Review
Investigating the Neuroprotective and Cognitive-Enhancing Effects of : A Systematic Review Focused on Inflammation, Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis.
The aging of the global population has increased the prevalence of neurodegenerative conditions. (BM), an herb with active compounds, such as bacosides A and B, betulinic acid, loliolide, asiatic acid, and quercetin, demonstrates the potential for brain health. Limited research has been conducted on the therapeutic applications of BM in neurodegenerative conditions. This systematic review aims to project BM's beneficial role in brain disorders. BM has anti-apoptotic and antioxidant actions and can repair damaged neurons, stimulate kinase activity, restore synaptic function, improve nerve transmission, and increase neuroprotection. The included twenty-two clinical trials demonstrated that BM can reduce Nuclear Factor-κB phosphorylation, improve emotional function, cognitive functions, anhedonia, hyperactivity, sleep routine, depression, attention deficit, learning problems, memory retention, impulsivity, and psychiatric problems. Moreover, BM can reduce the levels of pro-inflammatory biomarkers and oxidative stress. Here, we highlight that BM provides notable therapeutic benefits and can serve as a complementary approach for the care of patients with neurodegenerative conditions associated with brain disorders. This review adds to the growing interest in natural products and their potential therapeutic applications by improving our understanding of the mechanisms underlying cognitive function and neurodegeneration and informing the development of new therapeutic strategies for neurodegenerative diseases.
PubMed: 38671841
DOI: 10.3390/antiox13040393 -
Cureus Mar 2024Advanced pancreatic cancer is one of the prominent contributors to cancer-related mortality globally. Chemotherapy, especially gemcitabine, is generally used for the... (Review)
Review
Advanced pancreatic cancer is one of the prominent contributors to cancer-related mortality globally. Chemotherapy, especially gemcitabine, is generally used for the treatment of advanced pancreatic cancer. Despite the treatment, the fatality rate for advanced pancreatic cancer is alarmingly high. Thus, the dire need for better treatment alternatives has drawn focus to cancer vaccinations. The Wilms tumor gene (WT1), typically associated with Wilms tumor, is found to be excessively expressed in some cancers, such as pancreatic cancer. This characteristic feature is harvested to develop cancer vaccines against WT1. This review aims to systematically summarize the clinical trials investigating the efficacy and safety of WT1 vaccines in patients with advanced pancreatic cancer. An extensive literature search was conducted on databases Medline, Web of Science, ScienceDirect, and Google Scholar using the keywords "Advanced pancreatic cancer," "Cancer vaccines," "WT1 vaccines," and "Pulsed DC vaccines," and the results were exclusively studied to construct this review. WT1 vaccines work by introducing peptides from the WT1 protein to trigger an immune response involving cytotoxic T lymphocytes via antigen-presenting cells. Upon activation, these lymphocytes induce apoptosis in cancer cells by specifically targeting those with increased WT1 levels. WT1 vaccinations, which are usually given in addition to chemotherapy, have demonstrated clinically positive results and minimal side effects. However, there are several challenges to their widespread use, such as the immunosuppressive nature of tumors and heterogeneity in expression. Despite these limitations, the risk-benefit profile of cancer vaccines is encouraging, especially for the WT1 vaccine in the treatment of advanced pancreatic cancer. Considering the fledgling status of their development, large multicentric, variables-matched, extensive analysis across diverse demographics is considered essential.
PubMed: 38665761
DOI: 10.7759/cureus.56934 -
Biomedicine & Pharmacotherapy =... May 2024Propofol, a commonly used intravenous anesthetic, has demonstrated potential in protecting against myocardial ischemia/reperfusion injury (MIRI) based on preclinical... (Meta-Analysis)
Meta-Analysis Review
Propofol, a commonly used intravenous anesthetic, has demonstrated potential in protecting against myocardial ischemia/reperfusion injury (MIRI) based on preclinical animal studies. However, the clinical benefits of propofol in this context are subject to debate. We conducted a systematic search across eight databases to identify all relevant animal studies investigating the preventive effects of propofol on MIRI until October 30, 2023. We assessed the methodological quality of the included studies using SYRCLE's bias risk tool. Statistical analysis was performed using STATA 15.1. The primary outcome measures analyzed in this study were myocardial infarct size (IS) and myocardial injury biomarkers. This study presents a comprehensive analysis of 48 relevant animal studies investigating propofol's preventive effects on MIRI. Propofol administration demonstrated a reduction in myocardial IS and decreased levels of myocardial injury biomarkers (CK-MB, LDH, cTnI). Moreover, propofol improved myocardial function parameters (+dp/dtmax, -dP/dtmax, LVEF, LVFS), exhibited favorable effects on inflammatory markers (IL-6, TNF-α) and oxidative stress markers (SOD, MDA), and reduced myocardial cell apoptotic index (AI). These findings suggest propofol exerts cardioprotective effects by reducing myocardial injury, decreasing infarct size, and improving heart function. However, the absence of animal models that accurately represent comorbidities such as aging and hypertension, as well as inconsistent administration methods that align with clinical practice, may hinder its clinical translation. Further robust investigations are required to validate these findings, elucidate the underlying mechanisms of propofol, and facilitate its potential translation into clinical practice.
Topics: Propofol; Animals; Myocardial Infarction; Myocardial Reperfusion Injury; Oxidative Stress; Biomarkers; Anesthetics, Intravenous; Humans; Apoptosis
PubMed: 38640712
DOI: 10.1016/j.biopha.2024.116629 -
Journal of Cerebral Blood Flow and... Apr 2024Ischaemic stroke results in the formation of a cerebral infarction bordered by an ischaemic penumbra. Characterising the proteins within the ischaemic penumbra may... (Review)
Review
Ischaemic stroke results in the formation of a cerebral infarction bordered by an ischaemic penumbra. Characterising the proteins within the ischaemic penumbra may identify neuro-protective targets and novel circulating markers to improve patient care. This review assessed data from studies using proteomic platforms to compare ischaemic penumbra tissues to controls following experimental stroke in animal models. Proteins reported to differ significantly between penumbra and control tissues were analysed to identify protein-protein interactions and over-represented pathways. Sixteen studies using rat (n = 12), mouse (n = 2) or primate (n = 2) models were included. Heterogeneity in the design of the studies and definition of the penumbra were observed. Analyses showed high abundance of p53 in the penumbra within 24 hours of permanent ischaemic stroke and was implicated in driving apoptosis, cell cycle progression, and ATM- MAPK- and p53- signalling. Between 1 and 7 days after stroke there were changes in the abundance of proteins involved in the complement and coagulation pathways. Favourable recovery 1 month after stroke was associated with an increase in the abundance of proteins involved in wound healing. Poor recovery was associated with increases in prostaglandin signalling. Findings suggest that p53 may be a target for novel therapeutics for ischaemic stroke.
PubMed: 38639008
DOI: 10.1177/0271678X241248502 -
Iranian Journal of Basic Medical... 2024Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that has a high prevalence worldwide. Apigenin is a flavonoid present in several vegetables and fruits... (Review)
Review
Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that has a high prevalence worldwide. Apigenin is a flavonoid present in several vegetables and fruits and has anti-inflammatory, anti-oxidant, and anti-MetS properties. This study aims to systematically review the effects of apigenin against MetS and the relevant molecular and cellular mechanisms of action, pharmacokinetics features, and potential structure-activity relationship. Electronic databases including Scopus, PubMed, Science Direct and Cochrane Library were searched for in vivo, and in vitro, and human studies with the following keywords: "apigenin" and "metabolic syndrome or insulin resistance syndrome", "fatty liver", "hypertension or blood pressure", "diabetes or blood glucose", "dyslipidemia", "heart or cardiovascular " and "obesity" in title/abstract. Data were collected from 2000 until 2021 (up to April). Only papers published in the English language were included. Forty-six full-text articles out of 1016 retrieved papers were reviewed and underwent quality assessment by investigators. Anti-obesity activity of apigenin is mainly through attenuating adipocyte differentiation by suppressing the mitotic clonal expansion and the adipogenesis-related factors. Its anti-diabetic effects can be exerted through inhibition of protein tyrosine phosphatase1B expression, maintaining the activity of anti-oxidant enzymes, reducing intracellular ROS production, cellular DNA damage, protein carbonylation, and attenuating β-cell apoptosis. Moreover, apigenin could attenuate dyslipidemia and subsequent atherosclerotic conditions through down-regulating sterol regulatory element-binding proteins (SREBP)-1c, SREBP-2, stearyl-CoA desaturase-1, and 3-hydroxy-3-methyl-glutaryl-CoA reductase. Apigenin as a dietary bioactive compound would be a promising candidate for improving MetS and its components.
PubMed: 38629096
DOI: 10.22038/IJBMS.2024.71539.15558 -
Phytomedicine : International Journal... Jul 2024Cholestatic hepatitis is recognized as a significant contributor to the development of liver fibrosis and cirrhosis. As a well-known classic formula for the treatment of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cholestatic hepatitis is recognized as a significant contributor to the development of liver fibrosis and cirrhosis. As a well-known classic formula for the treatment of cholestatic hepatitis, Yinchenhao decoction (YCHD) is widely used in countries in Asia, including China, Japan, and Korea. However, in recent years, a risk of liver injury has been reported from Rheum palmatum L. and Gardenia jasmonoides J.Ellis which are the main ingredients of YCHD. Therefore, the question arises whether YCHD is still safe enough for the treatment of cholestatic hepatitis or whether an optimized ratio of ingredients should be applied. These is inevitable questions for the clinical application of YCHD.
PURPOSE
To provide a scientific basis for the clinical application of YCHD through a combination of meta-analysis and network pharmacology and to find the best ratio of components to ensure optimal therapeutic efficacy and safety. At the same time, a deeper understanding of the mechanisms of YCHD was explored.
METHODS
We retrieved relevant trials from various databases including PubMed, Web of Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP and Wanfang databases up to August 2023. After screening for inclusion and exclusion criteria, we assessed efficiency, ALT, AST, and TBIL as outcome parameters. The relevant data underwent a network meta-analysis using STATA 16.0 software. Based on network pharmacology, we screened the disease targets, active ingredients, and targets related to YCHD. The targets were visualized using Cytoscape 3.9.1. Then, potential mechanisms were explored based on bioinformatic techniques.
RESULTS
Twenty eligible studies were finally screened and a total of 1,591 patients who fulfilled the inclusion criteria were enrolled in the study. The meta-analysis results indicated that TG-c (treatment group c) [(Artemisia capillaris Thunb. : Gardenia jasminoides J.Ellis : Rheum palmatum L. = 10:5:2-10:5:3) + CT] was the most promising therapeutic approach, demonstrating superior efficacy and notable improvements in both AST and TBIL levels. For ALT, TG-d [(Artemisia capillaris : Gardenia jasminoides : Rheum palmatum = 5:1:1-5:2:1) + CT] exhibited the greatest potential as optimal therapy option. Based on the surface under the cumulative ranking curve (SUCRA) values, TG-c was the best therapy in terms of efficiency and improvement in TBIL levels, while TG-d was the most effective in reducing ALT levels. For AST levels, TG-e [(Artemisia capillaris : Gardenia jasminoides : Rheum palmatum = 5:2:2-5:3:3) + CT] was the most effective therapy. The comprehensive analysis revealed that TG-c exhibited the most pronounced efficacy. Combined network pharmacology, GO enrichment analysis and KEGG pathway enrichment analysis displayed that the key target genes of Artemisia capillaris, Rheum palmatum, and Gardenia jasminoides were closely involved in inflammation response, bile transport, apoptosis, oxidative stress, and regulation of leukocyte migration. Notably, bile secretion dominated the common pathway of the three herbs. On the other hand, Artemisia capillaris exhibited a unique mode of action by regulating the IL-17 signaling pathway, which may play a crucial role in its effectiveness.
CONCLUSION
Based on our findings, the optimal TG-C demonstrated the most favorable overall therapeutic efficacy by increasing the dosage of Artemisia capillaris while reducing the dosage of Gardenia jasminoides and Rheum palmatum. This is attributed to the potent ability of Artemisia capillaris. to effectively modulate the IL-17 signaling pathway, thereby exerting a beneficial therapeutic effect. Conversely, Gardenia jasminoides and Rheum palmatum may potentially enhance the activation of the NF-кB signaling pathway, thereby elevating the risk of hepatotoxicity.
Topics: Drugs, Chinese Herbal; Humans; Network Pharmacology; Network Meta-Analysis; Cholestasis; Rheum; Hepatitis
PubMed: 38583348
DOI: 10.1016/j.phymed.2024.155573 -
Journal of Alzheimer's Disease : JAD 2024Alzheimer's disease (AD) is a chronic neurodegenerative disease that affects the immune system due to the accumulation of amyloid-β (Aβ) and tau associated molecular...
BACKGROUND
Alzheimer's disease (AD) is a chronic neurodegenerative disease that affects the immune system due to the accumulation of amyloid-β (Aβ) and tau associated molecular pathology and other pathogenic processes. To address AD pathogenesis, various approaches had been conducted from drug development to lifestyle modification to reduce the prevalence of AD. Exercise is considered a prominent lifestyle modification to combat AD.
OBJECTIVE
This observation prompted us to review the literature on exercise related to immune genes in the cortex of animal models of AD. We focused on animal model studies due to their prevalence in this domain.
METHODS
The systematic review was conducted according to PRISMA standards using Web of Science (WoS) and PubMed databases. Any kind of genes, proteins, and molecular molecules were included in this systematic review. The list of these immune-related molecules was analyzed in the STRING database for functional enrichment analysis.
RESULTS
We found that 17 research studies discussed immune-related molecules and 30 immune proteins. These studies showed that exercise had the ability to ameliorate dysfunction in AD-related pathways, which led to decreasing the expression of microglia-related pathways and Th17-related immune pathways. As a result of decreasing the expression of immune-related pathways, the expression of apoptosis-related pathways was also decreasing, and neuronal survival was increased by exercise activity.
CONCLUSIONS
Based on functional enrichment analysis, exercise not only could reduce apoptotic factors and immune components but also could increase cell survival and Aβ clearance in cortex samples. PROSPERO ID: CRD42022326093.
Topics: Animals; Alzheimer Disease; Neurodegenerative Diseases; Amyloid beta-Peptides; Disease Models, Animal; Exercise
PubMed: 38578886
DOI: 10.3233/JAD-230803 -
BMC Oral Health Apr 2024The present study aimed to investigate the impact of resveratrol on oral neoplastic parameters through a systematic review and meta-analysis. Resveratrol, a naturally... (Meta-Analysis)
Meta-Analysis
The present study aimed to investigate the impact of resveratrol on oral neoplastic parameters through a systematic review and meta-analysis. Resveratrol, a naturally occurring polyphenol, has shown promising potential as a therapeutic agent in various cancer types, including oral neoplasms. Understanding the collective findings from existing studies can shed light on the efficacy and mechanisms of resveratrol in oral cancer management. The systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search was performed to identify relevant studies from various databases, registers, websites, and citation searches. The inclusion criteria encompassed in-vivo studies investigating the impact of resveratrol on oral neoplastic parameters in animal models. After screening and assessment, a total of five eligible studies were included in the meta-analysis. The meta-analysis of the selected studies revealed that resveratrol treatment exhibited a potential impact on reducing oral neoplastic proliferation and promoting neoplastic apoptosis. The combined analysis showed a statistically significant decrease in neoplastic parameters with an overall effect size (ES) of 0.85 (95% CI: [0.74, 0.98]). Subgroup analyses were conducted to explore potential variations among different cellular types and exposure compounds, providing further insights into the efficacy of resveratrol in specific contexts. This systematic review and meta-analysis support the potential of resveratrol as a promising therapeutic agent in oral cancer management. The findings indicate that resveratrol may effectively modulate neoplastic proliferation and apoptosis in various cellular types within animal models of oral cancer. However, further well-controlled studies and clinical trials are warranted to validate these observations and elucidate the underlying mechanisms of resveratrol's actions. Resveratrol holds promise as a complementary therapeutic approach in the prevention and treatment of oral neoplastic conditions.
Topics: Animals; Resveratrol; Mouth Neoplasms; Apoptosis
PubMed: 38575921
DOI: 10.1186/s12903-024-04045-8