A novel dammarane triterpenoid alleviates atherosclerosis by activating the LXRα pathway.
A novel dammarane triterpenoid alleviates atherosclerosis by activating the LXRα pathway.
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DOI：
10.1186/s13020-023-00758-0
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发表时间：
2023-06-15
期刊：
影响因子：
4.9
通讯作者：
Jia Y
中科院分区：
文献类型：
--
作者：
Huang Y;Ran X;Liu H;Luo M;Qin Y;Yan J;Li X;Jia Y
我们以前已经证明，化合物K可以减弱动脉粥样硬化病变的形成。因此，化合物K具有治疗动脉粥样硬化的潜力。如何提高复方K的可药用性，增强其抗动脉粥样硬化活性，是防治动脉粥样硬化的核心问题。CKN是一种化合物K的衍生物，在体外具有良好的抗动脉粥样硬化活性，已申请了国际专利。以雄性C57 BL/6 ApoE−/−小鼠为研究对象，通过高脂高胆碱饮食诱导动脉粥样硬化，并进行了体内研究。采用CCK-8法体外检测巨噬细胞的细胞毒活性。使用泡沫细胞，并进行细胞脂质测定用于体外研究。图像分析法测量动脉粥样硬化斑块面积和肝脏脂肪浸润面积。血清分析仪测定血脂和肝功能。免疫荧光和蛋白质印迹分析，探讨脂质流出相关蛋白的表达水平的变化。采用分子对接、报告基因实验和细胞热位移实验验证CKN与LXRα的相互作用。在确认CKN的治疗作用后，本研究采用分子对接、报告基因实验和细胞热位移实验等方法预测和研究CKN抗动脉粥样硬化的作用机制。CKN表现出最大的效力，在HHD喂养的ApoE−/−小鼠中，胸主动脉和头臂干上的正面动脉粥样硬化病变减少60.9%和48.1%，血浆脂质水平降低，血管斑块含量中的泡沫细胞水平降低。CKN可能通过激活ABCA 1，促进LXRα核转位，减轻LXRα激活的副作用，发挥抗动脉粥样硬化作用。我们的研究结果表明，CKN通过激活LXRα通路防止ApoE−/−小鼠动脉粥样硬化的形成。在线版本包含补充材料，可通过10.1186/s13020-023-00758-0获得。
We have previously demonstrated that ginsenoside compound K can attenuate the formation of atherosclerotic lesions. Therefore, ginsenoside compound K has potential for atherosclerosis therapy. How to improve the druggability and enhance the antiatherosclerotic activity of ginsenoside compound K are the core problems in the prevention and treatment of atherosclerosis. CKN is a ginsenoside compound K derivative that was previously reported to have excellent antiatherosclerotic activity in vitro, and we have applied for international patents for it. Male C57BL/6 ApoE−/− mice were fed a high-fat and high-choline diet to induce atherosclerosis and were subjected to in vivo studies. In vitro, the CCK-8 method was applied to evaluate cytotoxicity in macrophages. Foam cells were utilized, and cellular lipid determination was performed for in vitro studies. The area of atherosclerotic plaque and fatty infiltration of the liver were measured by image analysis. Serum lipid and liver function were determined by a seralyzer. Immunofluorescence and western blot analysis were conducted to explore the alterations in the expression levels of lipid efflux-related proteins. Molecular docking, reporter gene experiments and cellular thermal shift assays were used to verify the interaction between CKN and LXRα. After confirming the therapeutic effects of CKN, molecular docking, reporter gene experiments and cellular thermal shift assays were used to predict and investigate the antiatherosclerotic mechanisms of CKN. CKN exhibited the greatest potency, with a 60.9% and 48.1% reduction in en face atherosclerotic lesions on the thoracic aorta and brachiocephalic trunk, reduced plasma lipid levels and decreased foam cell levels in the vascular plaque content in HHD-fed ApoE−/− mice. Moreover, CKN in the present study may exert its antiatherosclerotic effects through activated ABCA1 by promoting LXRα nuclear translocation and reducing the adverse effects of LXRα activation. Our results revealed that CKN prevented the formation of atherosclerosis in ApoE−/− mice by activating the LXRα pathway. The online version contains supplementary material available at 10.1186/s13020-023-00758-0.
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影响因子：
30.5
作者：
Koelwyn GJ;Corr EM;Erbay E;Moore KJ
通讯作者：
Moore KJ
加速了探针疾病的动脉粥样硬化。
影响因子：
4.4
作者：
Muratsu J;Koseki M;Masuda D;Yasuga Y;Tomoyama S;Ataka K;Yagi Y;Nakagawa A;Hamada H;Fujita S;Hattori H;Ohama T;Nishida M;Hiraoka H;Matsuzawa Y;Yamashita S
通讯作者：
Yamashita S
DOI：
10.1016/s0140-6736(20)30925-9
发表时间：
2020-10-17
期刊：
Lancet (London, England)
影响因子：
--
作者：
GBD 2019 Diseases and Injuries Collaborators
通讯作者：
GBD 2019 Diseases and Injuries Collaborators
抑制 ASGR1 通过促进胆固醇排泄来降低脂质水平
影响因子：
64.8
作者：
Wang, Ju-Qiong;Li, Liang-Liang;Song, Bao-Liang
通讯作者：
Song, Bao-Liang
影响因子：
81.5
作者：
Libby, Peter;Buring, Julie E.;Lewis, Eldrin F.
通讯作者：
Lewis, Eldrin F.