Dietary 23-hydroxy ursolic acid protects against atherosclerosis and obesity by preventing dyslipidemia-induced monocyte priming and dysfunction.
Dietary 23-hydroxy ursolic acid protects against atherosclerosis and obesity by preventing dyslipidemia-induced monocyte priming and dysfunction.
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DOI：
10.1016/j.atherosclerosis.2018.06.882
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发表时间：
2018-08
期刊：
影响因子：
5.3
通讯作者：
Asmis R
中科院分区：
文献类型：
--
作者：
Nguyen HN;Ahn YJ;Medina EA;Asmis R
我们证明了饮食中的熊果酸(UA)可以缩小糖尿病小鼠的动脉粥样硬化病变范围，并改善其肾功能。基于对天然尿酸类似物的结构-功能分析，我们合成了23-羟基熊果酸(23-Ohua)，这是一种具有结构特征的化合物，与尿酸相比具有更高的生物利用度和抗动脉粥样硬化性能。本研究的目的是确定23-Ohua的抗肥胖和抗动脉粥样硬化作用及其作用机制。我们进行趋化试验，以确定植物化学物质对预置的THP-1单核细胞的IC50。我们用高脂饲料或高脂饲料添加0.05%尿酸或0.05%23-Ohua饲喂12周龄雌性−/−小鼠，并在6周和20周后测量单核细胞启动、体重增加和动脉粥样硬化病变大小。饮食中的UA和23-Ohua均可预防血脂异常引起的MKP-1活性丧失和高趋化活性，这是血液单核细胞启动和功能障碍的标志，但它们不影响血脂或血糖水平，也不影响WBC和单核细胞计数。20周后，与饲喂高脂饲料的对照组相比，服用23-Ohua的小鼠体重增加了11%，动脉粥样硬化斑块大小减少了40%，而UA仅减少了19%的病变大小，并且没有减少体重增加。饮食23-Ohua通过保护单核细胞免受代谢应激诱导的启动和功能障碍的影响，减少小鼠的体重增加和动脉粥样硬化形成。根据其作用机制，23-Ohua可能是防治肥胖和动脉粥样硬化的一种新的治疗方法。
We demonstrated that dietary ursolic acid (UA) reduces atherosclerotic lesion size and improves kidney function in diabetic mice. Based on structure-function analyses of naturally occurring UA analogs, we synthesized 23-hydroxy ursolic acid (23-OHUA), a compound with structural features predicted to enhance its bioavailability and anti-atherogenic properties compared to UA. The goal of this study was to determine the anti-obesogenic and atheroprotective properties of 23-OHUA and its mechanism of action. We performed chemotaxis assays to determine IC50 of phytochemicals on primed THP-1 monocytes. We fed 12-week old female LDLR−/− mice a high-fat diet (HFD) or a HFD supplemented with either 0.05% UA or 0.05% 23-OHUA, and measured monocyte priming, weight gain and atherosclerotic lesion size after 6 and 20 weeks. Both dietary UA and 23-OHUA prevented dyslipidemia-induced loss of MKP-1 activity, and hyper-chemotactic activity, a hallmark of blood monocytes priming and dysfunction, but they did not affect plasma lipids or blood glucose levels nor WBC and monocyte counts. After 20 weeks, mice fed 23-OHUA showed 11% less weight gain compared to HFD-fed control mice and a 40% reduction in atherosclerotic plaque size, whereas UA reduced lesion size by only 19% and did not reduce weight gain. Dietary 23-OHUA reduces weight gain and attenuates atherogenesis in mice by protecting monocytes against metabolic stress-induced priming and dysfunction. Based on its mechanism of action, 23-OHUA may represent a novel therapeutic approach for the prevention and treatment of obesity and atherosclerosis.
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DOI：
10.1161/atvbaha.111.238899
发表时间：
2012-02
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Ullevig S;Zhao Q;Lee CF;Seok Kim H;Zamora D;Asmis R
通讯作者：
Asmis R
影响因子：
7.9
作者：
Somova, LO;Nadar, A;Shode, FO
通讯作者：
Shode, FO
影响因子：
5.3
作者：
Asmis, R;Jelk, J
通讯作者：
Jelk, J
熊果酸同时靶向多种信号通路，抑制结肠癌细胞增殖并诱导细胞凋亡
影响因子：
3.7
作者：
Wang J;Liu L;Qiu H;Zhang X;Guo W;Chen W;Tian Y;Fu L;Shi D;Cheng J;Huang W;Deng W
通讯作者：
Deng W
影响因子：
7.4
作者：
Kim HS;Asmis R
通讯作者：
Asmis R