Gastroprotective [6]-Gingerol Aspirinate as a Novel Chemopreventive Prodrug of Aspirin for Colon Cancer.
Gastroprotective [6]-Gingerol Aspirinate as a Novel Chemopreventive Prodrug of Aspirin for Colon Cancer.
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DOI：
10.1038/srep40119
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发表时间：
2017-01-09
影响因子：
4.6
通讯作者：
Sang S
中科院分区：
文献类型：
--
作者：
Zhu Y;Wang F;Zhao Y;Wang P;Sang S
越来越多的研究表明，每日低剂量阿司匹林（阿萨）可减少心脏病和结肠直肠癌。然而，使用阿司匹林的主要限制是其副作用，导致胃肠道溃疡和出血。临床前研究表明，生姜成分改善ASA诱导的胃溃疡。我们设计并合成了一种新的阿司匹林前药--[6]-姜辣素阿司匹林酯（GAS）。我们的数据表明，GAS在体外发挥增强的抗癌特性，在小鼠中发挥上级胃保护作用。GAS也能够在胃酸中存活，并在肠道内层或吸收后分解，同时释放阿萨和[6]-姜辣素。我们进一步提出，气体失活考克斯-1和考克斯-2平等。我们的研究结果表明GAS的增强的抗癌特性沿着胃保护作用，表明GAS可以作为阿萨在炎症和增殖性疾病中的治疗等效物，而不会对胃粘膜产生有害影响。
A growing body of research suggests daily low-dose aspirin (ASA) reduces heart diseases and colorectal cancers. However, the major limitation to the use of aspirin is its side effect to cause ulceration and bleeding in the gastrointestinal tract. Preclinical studies have shown that ginger constituents ameliorate ASA-induced gastric ulceration. We here report the design and synthesis of a novel prodrug of aspirin, [6]-gingerol aspirinate (GAS). Our data show that GAS exerts enhanced anti-cancer properties in vitro and superior gastroprotective effects in mice. GAS was also able to survive stomach acid and decomposed in intestinal linings or after absorption to simultaneously release ASA and [6]-gingerol. We further present that GAS inactivates both COX-1 and COX-2 equally. Our results demonstrate the enhanced anticancer properties along with gastroprotective effects of GAS, suggesting that GAS can be a therapeutic equivalent for ASA in inflammatory and proliferative diseases without the deleterious effects on stomach mucosa.
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影响因子：
158.5
作者：
Bertagnolli, Monica M.;Eagle, Craig J.;Hawk, Ernest T.
通讯作者：
Hawk, Ernest T.
影响因子：
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作者：
Chen, Huadong;Lv, Lishuang;Sang, Shengmin
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Sang, Shengmin
影响因子：
158.5
作者：
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通讯作者：
Simes, John
影响因子：
158.5
作者：
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通讯作者：
NELSON, RS
影响因子：
2
作者：
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通讯作者：
van Oijen, M. G. H.