Mogrol Regulates the Expression of ATPase Na+/K+ Transport Subunit 3, Inhibits Cardiomyocyte Apoptosis, and Plays a Protective Role Against Myocardial Infarction.

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2025-03-02 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S490484

Feng Wang, Jinling Zhou, Weiwei Liu, Wei Wang, Boyan Tian, Jinyu Liu, Han Zhang, Peina He, Xiaoyun Yang, Li Yang, Yueheng Wang

{"title":"Mogrol Regulates the Expression of ATPase Na+/K+ Transport Subunit 3, Inhibits Cardiomyocyte Apoptosis, and Plays a Protective Role Against Myocardial Infarction.","authors":"Feng Wang, Jinling Zhou, Weiwei Liu, Wei Wang, Boyan Tian, Jinyu Liu, Han Zhang, Peina He, Xiaoyun Yang, Li Yang, Yueheng Wang","doi":"10.2147/DDDT.S490484","DOIUrl":null,"url":null,"abstract":"Background: With the advancements in medical technology, the death rate from myocardial infarction (MI), a prevalent heart illness, has gradually decreased; however, treatment hurdles and diagnostic issues remain. Mogrol is a naturally occurring plant extract with specific biological activities such as antioxidant, anti-inflammatory, antitumor, and hypoglycemic effects. These biological activities make it a potential therapeutic drug or research subject; however, its function in MI remains unclear.Methods: Potential targets of mogrol were searched using the MI Disease Database through online databases. Among the three intersecting genes, we focused on ATPase Na+/K+ transporting subunit 3A3, which is expressed at low levels in patients with MI. The preventive effect of mogrol against MI was investigated using cardiac ultrasonography, Western blotting, qPCR assay, Cell counting kit-8, Ca2+ concentration measurement, Na+/K+-ATPase, and flow cytometry.Results: The findings demonstrated that mogrol upregulated Ca2+ concentration and ATPase Na+/K+ transporting subunit 3 protein levels in cardiomyocytes and tissues, downregulated the apoptosis-related proteins B-cell lymphoma 2-like protein 4, cleaved-caspase-3, and upregulated B-cell lymphoma 2. These effects enhanced cardiac function, prevented cardiomyocyte apoptosis, encouraged cardiomyocyte proliferation, and protected mice from MI. Knocking down ATP1A3 can reverse the protective effect of Mogrol.Conclusion: Mogrol may have a protective effect on myocardial infarction by regulating Ca2+ concentration and the level of the ATPase Na+/K+ transport subunit 3 protein, as well as by regulating apoptosis-related proteins. Further revealing the pharmacokinetics of mogrol in vivo is expected to make it a subsequent drug for the treatment of cardiac infarction.","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1489-1502"},"PeriodicalIF":4.7000,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884411/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Design, Development and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/DDDT.S490484","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

Abstract

Background: With the advancements in medical technology, the death rate from myocardial infarction (MI), a prevalent heart illness, has gradually decreased; however, treatment hurdles and diagnostic issues remain. Mogrol is a naturally occurring plant extract with specific biological activities such as antioxidant, anti-inflammatory, antitumor, and hypoglycemic effects. These biological activities make it a potential therapeutic drug or research subject; however, its function in MI remains unclear.

Methods: Potential targets of mogrol were searched using the MI Disease Database through online databases. Among the three intersecting genes, we focused on ATPase Na+/K+ transporting subunit 3A3, which is expressed at low levels in patients with MI. The preventive effect of mogrol against MI was investigated using cardiac ultrasonography, Western blotting, qPCR assay, Cell counting kit-8, Ca2+ concentration measurement, Na+/K+-ATPase, and flow cytometry.

Results: The findings demonstrated that mogrol upregulated Ca2+ concentration and ATPase Na+/K+ transporting subunit 3 protein levels in cardiomyocytes and tissues, downregulated the apoptosis-related proteins B-cell lymphoma 2-like protein 4, cleaved-caspase-3, and upregulated B-cell lymphoma 2. These effects enhanced cardiac function, prevented cardiomyocyte apoptosis, encouraged cardiomyocyte proliferation, and protected mice from MI. Knocking down ATP1A3 can reverse the protective effect of Mogrol.

Conclusion: Mogrol may have a protective effect on myocardial infarction by regulating Ca2+ concentration and the level of the ATPase Na+/K+ transport subunit 3 protein, as well as by regulating apoptosis-related proteins. Further revealing the pharmacokinetics of mogrol in vivo is expected to make it a subsequent drug for the treatment of cardiac infarction.

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

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.