Nao-Xin-Qing tablet inhibits macrophage inflammatory response in atherosclerosis via AMPK-α/SIRT1/PPAR-γ pathway

IF 3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE
Guiting Zhou , Chenxi Wang , Zhichao Lin , Liwen Lin , Ruochen Zhu , Shushu Wang , Jiongbo Xu , Yuxin Xie , Yuling Zhang , Danling Cheng , Chun Zhou , Juan Lin , Haibiao Guo , Min Liu , Chuanjin Luo
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Abstract

Background and aim

Nao-Xin-Qing (NXQ) tablets are standardized proprietary herbal products containing an extract of Chinese persimmon leaves (Diospyros kaki L.f., World Checklist) and other natural ingredients. NXQ has also been indicated for atherosclerosis (AS), but the mechanisms of its antiatherosclerotic activity are unclear. In this study, its mechanisms were investigated by using preclinical models, and provide evidence for its potential application against cardiovascular disorders.

Experimental procedure

In vivo, the apolipoprotein E-deficient (ApoE−/−) mice were fed with a high-fat diet to induce AS. And the mice were treated with different concentrations of NXQ and Lipitor for 12 weeks. After the intervention, serum lipid levels and serum inflammatory factor levels were measured. The pathological changes in the aorta were observed by Oil-red-O staining and Hematoxylin and Eosin (HE) staining. Additionally, we investigated macrophage polarization both in vivo and in vitro. Using the NXQ fingerprint, we conducted network pharmacological analysis to predict and explore its antiatherosclerotic mechanism, which was validated in AS mice and LPS-induced macrophages.

Results

In our study, we found that NXQ significantly reduced atherosclerotic plaques in the aortic root and aorta and decreased serum lipid levels in HFD-fed ApoE−/− mice. Meanwhile, NXQ promoted M2 macrophage polarization, which is regulated by the AMPK-α/SIRT1/PPAR-γ axis. Importantly, suppressing AMPK-α eliminated the effect of NXQ on macrophages.

Conclusion

NXQ exerted a preventive effect on the development and progression of AS by promoting M2 macrophage polarization through modulation of the AMPK-α/SIRT1/PPAR-γ axis.

Abstract Image

野心清片通过 AMPK-α/SIRT1/PPAR-γ 通路抑制动脉粥样硬化中巨噬细胞的炎症反应
脑心清(NXQ)片是一种标准化的专利草药产品,含有柿叶提取物(Diospyros kaki L.f., World Checklist)和其他天然成分。NXQ也被用于动脉粥样硬化(AS),但其抗动脉粥样硬化活性的机制尚不清楚。本研究通过临床前模型研究其作用机制,为其在心血管疾病治疗中的潜在应用提供依据。实验方法:在体内,给载脂蛋白e缺乏(ApoE−/−)小鼠喂食高脂饲料以诱导AS。用不同浓度的NXQ和立普妥治疗小鼠12周。干预后,测量血脂水平和血清炎症因子水平。采用油红o染色、苏木精伊红(HE)染色观察主动脉的病理变化。此外,我们还研究了巨噬细胞在体内和体外的极化。我们利用NXQ指纹图谱进行网络药理分析,预测和探索其抗动脉粥样硬化机制,并在AS小鼠和lps诱导的巨噬细胞中得到验证。结果在我们的研究中,我们发现NXQ显著减少了hfd喂养的ApoE - / -小鼠主动脉根部和主动脉的动脉粥样硬化斑块,降低了血清脂质水平。同时,NXQ促进M2巨噬细胞极化,这一过程受AMPK-α/SIRT1/PPAR-γ轴调控。重要的是,抑制AMPK-α可消除NXQ对巨噬细胞的作用。结论nxq通过调节AMPK-α/SIRT1/PPAR-γ轴促进M2巨噬细胞极化,对AS的发生发展具有预防作用。
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来源期刊
Journal of Traditional and Complementary Medicine
Journal of Traditional and Complementary Medicine Medicine-Complementary and Alternative Medicine
CiteScore
9.30
自引率
6.70%
发文量
78
审稿时长
66 days
期刊介绍: eJTCM is committed to publish research providing the biological and clinical grounds for using Traditional and Complementary Medical treatments as well as studies that demonstrate the pathophysiological and molecular/biochemical bases supporting the effectiveness of such treatments. Review articles are by invitation only. eJTCM is receiving an increasing amount of submission, and we need to adopt more stringent criteria to select the articles that can be considered for peer review. Note that eJTCM is striving to increase the quality and medical relevance of the publications.
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