Vitexin mitigates oxidative stress, mitochondrial damage, pyroptosis and regulates small nucleolar RNA host gene 1/DNA methyltransferase 1/microRNA-495 axis in sepsis-associated acute lung injury.

IF 4.6 2区医学 Q2 IMMUNOLOGY

Inflammopharmacology Pub Date : 2024-12-06 DOI:10.1007/s10787-024-01609-6

Almaz Zaki, Mohd Mohsin, Salman Khan, Aman Khan, Shaniya Ahmad, Amit Verma, Shakir Ali, Tasneem Fatma, Mansoor Ali Syed

{"title":"Vitexin mitigates oxidative stress, mitochondrial damage, pyroptosis and regulates small nucleolar RNA host gene 1/DNA methyltransferase 1/microRNA-495 axis in sepsis-associated acute lung injury.","authors":"Almaz Zaki, Mohd Mohsin, Salman Khan, Aman Khan, Shaniya Ahmad, Amit Verma, Shakir Ali, Tasneem Fatma, Mansoor Ali Syed","doi":"10.1007/s10787-024-01609-6","DOIUrl":null,"url":null,"abstract":"Aim of the study: This study examined vitexin's effect on sepsis-induced acute lung injury. We used network pharmacology and in vivo and in vitro experiments were performed to elucidate vitexin's role in preventing pyroptosis and regulating small nucleolar RNA host gene 1 (SNHG1)/DNA methyltransferase 1 (DNMT1)/microRNA-495 (miR-495 axis.Materials and methods: We developed an acute lung injury model using C57BL/6 mice and MLE-12 cells. Through a combination of network pharmacology and in vitro screening, vitexin was identified as the most promising anti-inflammatory compound. Multiple techniques such as western blotting, real-time PCR, Hematoxylin and eosin staining, immunohistochemistry, and TUNEL assay were used. Additionally, immunofluorescence, DCFDA and TMRE staining, flow cytometry, methylation-specific PCR, and gene transfection techniques were performed to elucidate vitexin's potential targets and underlying mechanisms.Results: Vitexin treatment significantly reduced lung damage, neutrophil infiltration, and inflammation while improving tight junction integrity. In LPS-treated RAW264.7 macrophages and a septic mouse BALF-induced MLE-12 cell injury model, vitexin demonstrated anti-inflammatory effects, promoted M2 macrophage polarization, and enhanced regenerative markers. It also decreased oxidative stress, mitigated apoptosis and pyroptosis, and improved mitochondrial function. Our research uncovered a novel epigenetic regulatory mechanism involving lncRNA SNHG1, DNMT1, and miR-495.Conclusion: Vitexin's ability to reduce inflammation, counteract oxidative stress, and modulate epigenetic processes. These findings underscore the promising role of vitexin as a treatment for ALI generated by sepsis. The SNHG1/miR-495 axis, which has been identified, represents a new target for future therapies in acute lung injury.","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6000,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Inflammopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10787-024-01609-6","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Aim of the study: This study examined vitexin's effect on sepsis-induced acute lung injury. We used network pharmacology and in vivo and in vitro experiments were performed to elucidate vitexin's role in preventing pyroptosis and regulating small nucleolar RNA host gene 1 (SNHG1)/DNA methyltransferase 1 (DNMT1)/microRNA-495 (miR-495 axis.

Materials and methods: We developed an acute lung injury model using C57BL/6 mice and MLE-12 cells. Through a combination of network pharmacology and in vitro screening, vitexin was identified as the most promising anti-inflammatory compound. Multiple techniques such as western blotting, real-time PCR, Hematoxylin and eosin staining, immunohistochemistry, and TUNEL assay were used. Additionally, immunofluorescence, DCFDA and TMRE staining, flow cytometry, methylation-specific PCR, and gene transfection techniques were performed to elucidate vitexin's potential targets and underlying mechanisms.

Results: Vitexin treatment significantly reduced lung damage, neutrophil infiltration, and inflammation while improving tight junction integrity. In LPS-treated RAW264.7 macrophages and a septic mouse BALF-induced MLE-12 cell injury model, vitexin demonstrated anti-inflammatory effects, promoted M2 macrophage polarization, and enhanced regenerative markers. It also decreased oxidative stress, mitigated apoptosis and pyroptosis, and improved mitochondrial function. Our research uncovered a novel epigenetic regulatory mechanism involving lncRNA SNHG1, DNMT1, and miR-495.

Conclusion: Vitexin's ability to reduce inflammation, counteract oxidative stress, and modulate epigenetic processes. These findings underscore the promising role of vitexin as a treatment for ALI generated by sepsis. The SNHG1/miR-495 axis, which has been identified, represents a new target for future therapies in acute lung injury.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Inflammopharmacology IMMUNOLOGYTOXICOLOGY-TOXICOLOGY

CiteScore

8.00

自引率

3.40%

发文量

200

期刊介绍： Inflammopharmacology is the official publication of the Gastrointestinal Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the Hungarian Experimental and Clinical Pharmacology Society (HECPS). Inflammopharmacology publishes papers on all aspects of inflammation and its pharmacological control emphasizing comparisons of (a) different inflammatory states, and (b) the actions, therapeutic efficacy and safety of drugs employed in the treatment of inflammatory conditions. The comparative aspects of the types of inflammatory conditions include gastrointestinal disease (e.g. ulcerative colitis, Crohn''s disease), parasitic diseases, toxicological manifestations of the effects of drugs and environmental agents, arthritic conditions, and inflammatory effects of injury or aging on skeletal muscle. The journal has seven main interest areas: -Drug-Disease Interactions - Conditional Pharmacology - i.e. where the condition (disease or stress state) influences the therapeutic response and side (adverse) effects from anti-inflammatory drugs. Mechanisms of drug-disease and drug disease interactions and the role of different stress states -Rheumatology - particular emphasis on methods of measurement of clinical response effects of new agents, adverse effects from anti-rheumatic drugs -Gastroenterology - with particular emphasis on animal and human models, mechanisms of mucosal inflammation and ulceration and effects of novel and established anti-ulcer, anti-inflammatory agents, or antiparasitic agents -Neuro-Inflammation and Pain - model systems, pharmacology of new analgesic agents and mechanisms of neuro-inflammation and pain -Novel drugs, natural products and nutraceuticals - and their effects on inflammatory processes, especially where there are indications of novel modes action compared with conventional drugs e.g. NSAIDs -Muscle-immune interactions during inflammation [...]