Beijing University of Chinese Medicine Affiliated Shenzhen Hospital, Shenzhen, China.
The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou University of Traditional Chinese Medicine, Guangzhou, 510405, China.
BMC Complement Med Ther. 2024 Jan 24;24(1):53. doi: 10.1186/s12906-024-04356-x.
Atherosclerosis (AS) is a fundamental pathological state in various cardiovascular diseases. Geniposide, which is the main active component of Gardenia jasminides, is effective against AS. However, the underlying molecular mechanisms remain unclear. Here, we sought to elucidate them.
The targets of AS and geniposide were collected from online public databases. The potential mechanism of Geniposide in treating AS was predicted by constructing a protein-protein interaction (PPI) network and conducting Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses. Hub proteins and core pathways were verified by molecular docking and in vivo experiments. Moreover, the effect of geniposide on AS was assessed by measuring the atherosclerotic plaque area in the thoracic aorta of mice. ApoE mice were used to establish AS models and randomly divided into different groups. Two different doses of geniposide were administered to the mice. Hematoxylin and eosin (HE) staining was performed to evaluate the effects of geniposide on AS. Oil Red O and Sirius Red staining were used to evaluate plaque stability. The protein expression of key markers involved in the signalling pathways was examined using western blotting and immunofluorescence.
A total of 239 active targets, 3418 AS-related disease targets, and 129 overlapping targets were identified. Hub genes were detected, and molecular docking revealed that geniposide strongly interacted with hub proteins (AKT1, VEGFA, CTNNB1, MMP9, and EGFR). Moreover, 109 signalling pathways, including the Rap1 signalling pathway, were identified using enrichment analysis. The results of in vivo experiments demonstrated that geniposide reduced body weight and blood lipid levels, alleviated the formation of atherosclerotic plaques, enhanced plaque stability, and inhibited inflammation, at least partially, by activating the Rap1/PI3K/Akt signalling pathway in ApoE mice.
Geniposide can alleviate AS and enhance the stability of atherosclerotic plaques by regulating the Rap1/PI3K/Akt signalling pathway.
动脉粥样硬化（AS）是各种心血管疾病的基本病理状态。栀子苷是栀子的主要活性成分，对 AS 有治疗作用。然而，其潜在的分子机制尚不清楚。在这里，我们试图阐明这些机制。
从在线公共数据库中收集 AS 和栀子苷的靶点。通过构建蛋白质-蛋白质相互作用（PPI）网络，并进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析，预测栀子苷治疗 AS 的潜在机制。通过分子对接和体内实验验证了关键蛋白和核心通路。此外，通过测量小鼠胸主动脉粥样硬化斑块面积来评估栀子苷对 AS 的影响。使用载脂蛋白 E（ApoE）小鼠建立 AS 模型，并将其随机分为不同组。给小鼠给予两种不同剂量的栀子苷。进行苏木精和伊红（HE）染色以评估栀子苷对 AS 的影响。油红 O 和天狼猩红染色用于评估斑块稳定性。使用 Western blot 和免疫荧光法检测参与信号通路的关键标记物的蛋白表达。
共鉴定出 239 个活性靶标、3418 个 AS 相关疾病靶标和 129 个重叠靶标。检测到关键基因，并通过分子对接发现栀子苷与关键蛋白（AKT1、VEGFA、CTNNB1、MMP9 和 EGFR）强烈相互作用。此外，通过富集分析还鉴定出 109 条信号通路，包括 Rap1 信号通路。体内实验结果表明，栀子苷通过激活 ApoE 小鼠的 Rap1/PI3K/Akt 信号通路，减轻体重和血脂水平，减轻动脉粥样硬化斑块的形成，增强斑块稳定性，并抑制炎症。
栀子苷通过调节 Rap1/PI3K/Akt 信号通路减轻 AS 并增强动脉粥样硬化斑块的稳定性。
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