PDF(Pubmed)
Abstract：
UNASSIGNED: Atherosclerosis (AS) is a chronic arterial pathology and a leading cause of vascular disease-related mortality. Fatty streaks in the arterial wall develop into atherosclerosis and characteristic plaques. Clinical interventions typically involve lipid-lowering medications and drugs for stabilizing vulnerable plaques, but no direct therapeutic agent specifically targets atherosclerosis. Garlic, also locally known as DASUAN, is recognized as a widely sold herbal dietary supplement esteemed for its cardiovascular benefits. However, the specific mechanisms of garlic\'s anti-atherosclerotic effects remain unclear.
UNASSIGNED: This study aims to elucidate the pharmacological mechanisms through which garlic ameliorates atherosclerosis.
UNASSIGNED: The study identified the major active components and targets of garlic by screening the TCMSP, TCM-ID, and, ETCM databases. Atherosclerosis-associated targets were obtained from the DisGeNET, GeneCards, and DiGSeE databases, and garlic intervention targets were determined through intersection. Utilizing the intersected genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using R software. A garlic component-disease target network was constructed using Cytoscape. RNA-seq datasets from the GEO database were utilized to identify differentially expressed genes (DEGs) associated with atherosclerosis. The target genes were intersected with DEGs and the FerrDb (ferroptosis database). Molecular docking predicted the binding interactions between active components and the core targets. In vitro and in vivo experiments validated the identified core targets.
UNASSIGNED: The integration of garlic drug targets with atherosclerotic disease targets identified 230 target genes. Intersection with RNA-seq DEGs revealed 15 upregulated genes, including 8 target genes related to ferroptosis. Molecular docking indicated favorable affinities between garlic active components [Sobrol A, (+)-L-Alliin, Benzaldoxime, Allicin] and target genes (DPP4, ALOX5, GPX4). Experimental validation showed that GARLIC reduces the expression of ferroptosis-related genes in AS, suggesting its therapeutic potential through the regulation of ferroptosis.
UNASSIGNED: Garlic ameliorates atherosclerosis by targeting intra-plaque ferroptosis and reducing lipid peroxidation. These findings provide novel insights into the pharmacological mechanisms underlying the efficacy of garlic in treating AS.
UNASSIGNED: This study aims to elucidate the pharmacological mechanisms through which garlic ameliorates atherosclerosis.
UNASSIGNED: The study identified the major active components and targets of garlic by screening the TCMSP, TCM-ID, and, ETCM databases. Atherosclerosis-associated targets were obtained from the DisGeNET, GeneCards, and DiGSeE databases, and garlic intervention targets were determined through intersection. Utilizing the intersected genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using R software. A garlic component-disease target network was constructed using Cytoscape. RNA-seq datasets from the GEO database were utilized to identify differentially expressed genes (DEGs) associated with atherosclerosis. The target genes were intersected with DEGs and the FerrDb (ferroptosis database). Molecular docking predicted the binding interactions between active components and the core targets. In vitro and in vivo experiments validated the identified core targets.
UNASSIGNED: The integration of garlic drug targets with atherosclerotic disease targets identified 230 target genes. Intersection with RNA-seq DEGs revealed 15 upregulated genes, including 8 target genes related to ferroptosis. Molecular docking indicated favorable affinities between garlic active components [Sobrol A, (+)-L-Alliin, Benzaldoxime, Allicin] and target genes (DPP4, ALOX5, GPX4). Experimental validation showed that GARLIC reduces the expression of ferroptosis-related genes in AS, suggesting its therapeutic potential through the regulation of ferroptosis.
UNASSIGNED: Garlic ameliorates atherosclerosis by targeting intra-plaque ferroptosis and reducing lipid peroxidation. These findings provide novel insights into the pharmacological mechanisms underlying the efficacy of garlic in treating AS.
摘要：
动脉粥样硬化(AS)是一种慢性动脉病理学和血管疾病相关死亡的主要原因。动脉壁中的脂肪条纹发展成动脉粥样硬化和特征性斑块。临床干预通常涉及降脂药物和稳定易损斑块的药物。但没有直接的治疗药物特异性靶向动脉粥样硬化。大蒜,在当地也被称为Dasuan，被认为是一种广泛销售的草药膳食补充剂，因其心血管益处而受到尊敬。然而,大蒜抗动脉粥样硬化作用的具体机制尚不清楚。
■本研究旨在阐明大蒜改善动脉粥样硬化的药理机制。
■该研究通过筛选TCMSP确定了大蒜的主要活性成分和靶标，TCM-ID,and,ETCM数据库。动脉粥样硬化相关的目标是从DisGeNET获得的，GeneCards,和DiGSeE数据库，并通过交叉确定大蒜干预目标。利用交叉的基因，使用R软件进行基因本体论(GO)和京都基因和基因组百科全书(KEGG)途径富集分析。使用Cytoscape构建了大蒜成分-疾病目标网络。来自GEO数据库的RNA-seq数据集用于鉴定与动脉粥样硬化相关的差异表达基因(DEG)。将靶基因与DEGs和FerrDb(铁沉积数据库)相交。分子对接预测了活性成分与核心靶标之间的结合相互作用。体外和体内实验验证了所鉴定的核心靶标。
■大蒜药物靶标与动脉粥样硬化疾病靶标的整合确定了230个靶标基因。与RNA-seqDEGs的交叉显示了15个上调的基因，包括8个与铁凋亡相关的靶基因。分子对接表明大蒜活性成分之间具有良好的亲和力[SobrolA，(+)-L-Alliin,苯甲醛肟,大蒜素]和靶基因(DPP4、ALOX5、GPX4)。实验验证表明，GARLIC降低了AS中铁凋亡相关基因的表达，通过铁凋亡的调节表明其治疗潜力。
■大蒜通过靶向斑块内铁死亡和减少脂质过氧化来改善动脉粥样硬化。这些发现为大蒜治疗AS功效的药理学机制提供了新的见解。
■本研究旨在阐明大蒜改善动脉粥样硬化的药理机制。
■该研究通过筛选TCMSP确定了大蒜的主要活性成分和靶标，TCM-ID,and,ETCM数据库。动脉粥样硬化相关的目标是从DisGeNET获得的，GeneCards,和DiGSeE数据库，并通过交叉确定大蒜干预目标。利用交叉的基因，使用R软件进行基因本体论(GO)和京都基因和基因组百科全书(KEGG)途径富集分析。使用Cytoscape构建了大蒜成分-疾病目标网络。来自GEO数据库的RNA-seq数据集用于鉴定与动脉粥样硬化相关的差异表达基因(DEG)。将靶基因与DEGs和FerrDb(铁沉积数据库)相交。分子对接预测了活性成分与核心靶标之间的结合相互作用。体外和体内实验验证了所鉴定的核心靶标。
■大蒜药物靶标与动脉粥样硬化疾病靶标的整合确定了230个靶标基因。与RNA-seqDEGs的交叉显示了15个上调的基因，包括8个与铁凋亡相关的靶基因。分子对接表明大蒜活性成分之间具有良好的亲和力[SobrolA，(+)-L-Alliin,苯甲醛肟,大蒜素]和靶基因(DPP4、ALOX5、GPX4)。实验验证表明，GARLIC降低了AS中铁凋亡相关基因的表达，通过铁凋亡的调节表明其治疗潜力。
■大蒜通过靶向斑块内铁死亡和减少脂质过氧化来改善动脉粥样硬化。这些发现为大蒜治疗AS功效的药理学机制提供了新的见解。
