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肉苁蓉苯乙醇苷提取物改善载脂蛋白E缺陷小鼠的动脉粥样硬化并调节肠道PPARγ-LXRα-ABCA1通路。

Phenylethanoid glycosides extract from Cistanche deserticola ameliorates atherosclerosis in apolipoprotein E-deficient mice and regulates intestinal PPARγ-LXRα-ABCA1 pathway.

作者信息

Jia Xiubin, Liu Boyan, Xue Junli, Liu Yunchao, Zhang Jingjun, Qin Shucun, Zhang Ying

机构信息

School of Pharmaceutical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai'an, Shandong Province, People's Republic of China.

The Second Affiliated Hospital of Shandong First Medical University, Tai'an, Shandong Province, People's Republic of China.

出版信息

J Pharm Pharmacol. 2023 Apr 17;75(5):677-685. doi: 10.1093/jpp/rgad015.

Abstract

OBJECTIVES

This study was aimed to evaluate the protective effects of phenylethanoid glycosides extract from Cistanche deserticola against atherosclerosis and its molecular mechanism.

METHODS

Total phenylethanoid glycosides were extracted and purified from C. deserticola, and the C. deserticola extract (CDE) was used to treat a mice model of atherosclerosis.

KEY FINDINGS

CDE containing 81.00% total phenylethanoid glycosides, with the contents of echinacoside and acteoside being 31.36% and 7.23%, respectively. A 13-week of CDE supplementation (1000 mg/kg body weight/day) significantly reduced atherosclerotic lesions in the aortic sinus and entire aorta in ApoE-/- mice fed with a high-fat diet. In addition, varying doses of CDE (250, 500 and 1000 mg/kg body weight/day) lowered plasma total cholesterol, triglyceride and non-high-density lipoprotein cholesterol levels. Transcriptomic analysis of the small intestine revealed the changes enriched in cholesterol metabolic pathway and the activation of Abca1 gene. Further validation using real-time quantitative PCR and western blot confirmed that CDE significantly increased the mRNA levels and protein expressions of ABCA1, LXRα and PPARγ.

CONCLUSIONS

Our results demonstrate the beneficial effects of C. deserticola on atherosclerotic plaques and lipid homeostasis, and it is, at least partially, by activating PPARγ-LXRα-ABCA1 pathway in small intestine.

摘要

目的

本研究旨在评估肉苁蓉苯乙醇苷提取物对动脉粥样硬化的保护作用及其分子机制。

方法

从肉苁蓉中提取并纯化总苯乙醇苷,用肉苁蓉提取物(CDE)处理动脉粥样硬化小鼠模型。

主要发现

CDE中总苯乙醇苷含量为81.00%,紫锥菊苷和毛蕊花糖苷含量分别为31.36%和7.23%。对高脂饮食喂养的ApoE-/-小鼠补充13周CDE(1000毫克/千克体重/天)可显著减少主动脉窦和整个主动脉的动脉粥样硬化病变。此外,不同剂量的CDE(250、500和1000毫克/千克体重/天)可降低血浆总胆固醇、甘油三酯和非高密度脂蛋白胆固醇水平。小肠转录组分析显示胆固醇代谢途径变化丰富,Abca1基因激活。使用实时定量PCR和蛋白质印迹进一步验证证实,CDE显著提高了ABCA1、LXRα和PPARγ的mRNA水平和蛋白质表达。

结论

我们的结果证明了肉苁蓉对动脉粥样硬化斑块和脂质稳态具有有益作用,且至少部分是通过激活小肠中的PPARγ-LXRα-ABCA1途径实现的。

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