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基于网络药理学和药理实验揭示阿美丹抗动脉粥样硬化的作用

Uncovering the Role of Anmeidan against Atherosclerosis from Integrated Network Pharmacology and Pharmacological Experiments.

作者信息

Zheng Yuting, Wang Jianxiang, Pan Chengcheng, Song Jihong, Li Xingyue, Ta Wenjing, Lu Wen

机构信息

School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, China.

出版信息

Comb Chem High Throughput Screen. 2025;28(6):915-930. doi: 10.2174/0113862073281925240417062009.

DOI:10.2174/0113862073281925240417062009
PMID:38676497
Abstract

BACKGROUND

Atherosclerosis (AS) is the leading cause of mortality in elderly individuals worldwide. Anmeidan (AMD) is a Traditional Chinese Medicine (TCM) formula composed of many herbs, many of which have been accepted for treating AS. This study aimed to explore whether AMD can inhibit the progress of AS and its possible mechanism.

METHODS

ApoE mice were used to establish the AS model and evaluate the therapeutic effect of AMD on AS. Based on network pharmacology technology, the potential mechanism of AMD for treating AS was explored, and lipid metabolism pathways related to AS were mainly studied. Next, the effects of AMD on liver lipid levels, antioxidant capacity, liver tissue morphology, and gene expression related to lipid metabolism in ApoE mice were investigated. Cellular experiments were performed to confirm the lipid-lowering effect of AMD. Finally, the AMD composition was determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

RESULTS

In ApoE mice, AMD effectively alleviated AS by reducing serum total cholesterol, triglyceride, low-density lipoprotein levels, and plaque area, and increasing high-density lipoprotein levels. Network pharmacology indicated that AMD may suppress AS by regulating lipid metabolism pathways with multiple TCM components, which was consistent with the results of experiments and LC-MS/MS component identification. AMD significantly reduced liver lipid aggregation, intensified antioxidant enzyme activity, and upregulated the mRNA levels of ABCA1, ABCG1, and LDLR with increased cholesterol efflux. In addition, AMD decreased cholesterol levels in foam cells.

CONCLUSION

This study confirmed that AMD could treat AS by regulating lipid metabolism and preliminarily explored the related mechanism. These findings provide new ideas for the treatment of AS with TCM.

摘要

背景

动脉粥样硬化(AS)是全球老年个体死亡的主要原因。安脉丹(AMD)是一种由多种草药组成的中药配方,其中许多草药已被认可用于治疗AS。本研究旨在探讨AMD是否能抑制AS的进展及其可能的机制。

方法

使用载脂蛋白E(ApoE)小鼠建立AS模型,并评估AMD对AS的治疗效果。基于网络药理学技术,探索AMD治疗AS的潜在机制,主要研究与AS相关的脂质代谢途径。接下来,研究AMD对ApoE小鼠肝脏脂质水平、抗氧化能力、肝脏组织形态以及与脂质代谢相关基因表达的影响。进行细胞实验以证实AMD的降脂作用。最后,采用液相色谱 - 串联质谱法(LC-MS/MS)测定AMD的成分。

结果

在ApoE小鼠中,AMD通过降低血清总胆固醇、甘油三酯、低密度脂蛋白水平和斑块面积,以及提高高密度脂蛋白水平,有效缓解了AS。网络药理学表明,AMD可能通过多种中药成分调节脂质代谢途径来抑制AS,这与实验结果和LC-MS/MS成分鉴定结果一致。AMD显著减少肝脏脂质聚集,增强抗氧化酶活性,并上调ABCA1、ABCG1和LDLR的mRNA水平,同时增加胆固醇流出。此外,AMD降低了泡沫细胞中的胆固醇水平。

结论

本研究证实AMD可通过调节脂质代谢治疗AS,并初步探索了相关机制。这些发现为中药治疗AS提供了新思路。

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Taohong Siwu decoction ameliorates atherosclerosis in rats possibly through toll-like receptor 4/myeloid differentiation primary response protein 88/nuclear factor-κB signal pathway.
桃红四物汤通过 Toll 样受体 4/髓样分化初级反应蛋白 88/核因子-κB 信号通路改善大鼠动脉粥样硬化。
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Protocatechuic acid alleviates TMAO-aggravated atherosclerosis mitigating inflammation, regulating lipid metabolism, and reshaping gut microbiota.原儿茶酸缓解 TMAO 加剧的动脉粥样硬化 减轻炎症,调节脂质代谢,重塑肠道微生物群。
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