Screening potential mitochondria-targeting compounds from traditional Chinese medicines using a mitochondria-based centrifugal ultrafiltration/liquid chromatography/mass spectrometry method.
Screening potential mitochondria-targeting compounds from traditional Chinese medicines using a mitochondria-based centrifugal ultrafiltration/liquid chromatography/mass spectrometry method.
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利用基于线粒体的离心超滤/液相色谱/质谱方法筛选中药中潜在的线粒体靶向化合物
DOI：
10.1016/j.jpha.2018.06.001
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发表时间：
2018-08
影响因子：
8.8
通讯作者：
Cai SQ
中科院分区：
文献类型：
--
作者：
Yang XX;Zhou YZ;Xu F;Yu J;Gegentana;Shang MY;Wang X;Cai SQ
线粒体调节许多重要的细胞过程，包括能量产生、凋亡性细胞死亡、氧化应激、钙稳态和脂质代谢。在这里，我们应用了一种有效的基于芦荟的离心超滤/液相色谱/质谱（LC/MS）方法，也被称为芦荟靶向生物活性成分的筛选方法（SM-MBC）。该方法可以从传统中药中寻找天然的具有抗肿瘤活性的化合物，包括黄芪（PR）和甘草（CR）。从两种中药提取物中共分离出23个活性成分。在这23个目标化合物中，经LC/MS鉴定了17个化合物，其中12个为新的靶向化合物。其中，6种活性化合物进行了体外药理学试验分析，发现能够影响线粒体功能。我们还研究了命中化合物对HepG 2细胞增殖和缺氧/复氧损伤诱导的心肌细胞活力丧失的影响。这些结果有助于从线粒体水平深入了解中药的治疗作用机制，并为开发以中药为先导化合物的新型药物奠定基础。最后，我们表明，SM-MBC是一个有效的协议，从复杂的样品，如PR和CR提取物中快速筛选靶向成分。
Mitochondria regulate numerous crucial cell processes, including energy production, apoptotic cell death, oxidative stress, calcium homeostasis and lipid metabolism. Here, we applied an efficient mitochondria-based centrifugal ultrafiltration/liquid chromatography/mass spectrometry (LC/MS) method, also known as screening method for mitochondria-targeted bioactive constituents (SM-MBC). This method allowed searching natural mitochondria-targeting compounds from traditional Chinese medicines (TCMs), including Puerariae Radix (PR) and Chuanxiong Radix (CR). A total of 23 active compounds were successfully discovered from the two TCMs extracts. Among these 23 hit compounds, 17 were identified by LC/MS, 12 of which were novel mitochondria-targeting compounds. Among these, 6 active compounds were analyzed in vitro for pharmacological tests and found able to affect mitochondrial functions. We also investigated the effects of the hit compounds on HepG2 cell proliferation and on loss of cardiomyocyte viability induced by hypoxia/reoxygenation injury. The results obtained are useful for in-depth understanding of mechanisms underlying TCMs therapeutic effects at mitochondria level and for developing novel potential drugs using TCMs as lead compounds. Finally, we showed that SM-MBC was an efficient protocol for the rapid screening of mitochondria-targeting constituents from complex samples such as PR and CR extracts.
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DOI：
10.1016/j.biocel.2015.01.020
发表时间：
2015-06-01
影响因子：
4
作者：
Iannetti, Eligio F.;Willems, Peter H. G. M.;Koopman, Werner J. H.
通讯作者：
Koopman, Werner J. H.
影响因子：
1.7
作者：
Lu, Jing;Xie, Yuanyuan;Yuan, Dan
通讯作者：
Yuan, Dan
影响因子：
4.1
作者：
Du, G.;Zhao, H. Y.;Wang, Y. T.
通讯作者：
Wang, Y. T.
影响因子：
4.4
作者：
Sahdeo S;Tomilov A;Komachi K;Iwahashi C;Datta S;Hughes O;Hagerman P;Cortopassi G
通讯作者：
Cortopassi G
影响因子：
6.1
作者：
Gao, Qin;Pan, Hong-Yang;Xia, Qiang
通讯作者：
Xia, Qiang