Raging the War Against Inflammation With Natural Products.
Raging the War Against Inflammation With Natural Products.
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DOI：
10.3389/fphar.2018.00976
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发表时间：
2018
影响因子：
5.6
通讯作者：
Ahmad W
中科院分区：
文献类型：
--
作者：
Attiq A;Jalil J;Husain K;Ahmad W
在过去的几十年中，非甾体抗炎药（NSAID）是治疗包括类风湿性关节炎在内的许多炎症性疾病的首选药物。NSAIDs通过抑制环氧化酶产生抗炎活性，环氧化酶负责花生四烯酸转化为洋地黄素。同样地，环氧化酶-2抑制剂（考克斯-2）选择性地抑制考克斯-2酶并产生显著的抗炎、镇痛和解热活性，而不产生考克斯-1相关的胃肠道和肾脏副作用。在过去的二十年中，已经开发了许多选择性考克斯-2抑制剂（COXIB）并批准用于各种炎症病症。然而，来自临床试验的数据表明，长期使用考克斯-2抑制剂也与危及生命的心血管副作用相关，包括缺血性心力衰竭和心肌感染。天然产物的次级代谢产物为开发新型抗炎化合物提供了巨大的希望。尽管大多数基于天然产物的化合物对考克斯-1表现出更高的选择性。然而，数据表明，轻微的结构修饰可以有助于开发具有相当功效和有限副作用的考克斯-2选择性次级代谢产物。本文综述了具有显著抑制考克斯-2和考克斯-2介导的PGE 2活性的陆地和海洋来源的次级代谢产物，因为预期具有抑制考克斯-2介导的PGE 2产生能力的分离物将用于抑制炎症及其经典体征和症状。此外，本文还对小檗碱、贝壳杉烯酸、α-香附酮、姜黄素和莪术二醇等潜在的先导化合物进行了结构-活性关系（SAR）研究，并对其研究现状进行了综述。
Over the last few decade Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are the drugs of choice for treating numerous inflammatory diseases including rheumatoid arthritis. The NSAIDs produces anti-inflammatory activity via inhibiting cyclooxygenase enzyme, responsible for the conversation of arachidonic acid to prostaglandins. Likewise, cyclooxegenase-2 inhibitors (COX-2) selectively inhibit the COX-2 enzyme and produces significant anti-inflammatory, analgesic, and anti-pyretic activity without producing COX-1 associated gastrointestinal and renal side effects. In last two decades numerous selective COX-2 inhibitors (COXIBs) have been developed and approved for various inflammatory conditions. However, data from clinical trials have suggested that the prolong use of COX-2 inhibitors are also associated with life threatening cardiovascular side effects including ischemic heart failure and myocardial infection. In these scenario secondary metabolites from natural product offers a great hope for the development of novel anti-inflammatory compounds. Although majority of the natural product based compounds exhibit more selectively toward COX-1. However, the data suggest that slight structural modification can be helpful in developing COX-2 selective secondary metabolites with comparative efficacy and limited side effects. This review is an effort to highlight the secondary metabolites from terrestrial and marine source with significant COX-2 and COX-2 mediated PGE2 inhibitory activity, since it is anticipated that isolates with ability to inhibit COX-2 mediated PGE2 production would be useful in suppressing the inflammation and its classical sign and symptoms. Moreover, this review has highlighted the potential lead compounds including berberine, kaurenoic acid, α-cyperone, curcumin, and zedoarondiol for further development with the help of structure–activity relationship (SAR) studies and their current status.
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影响因子：
--
作者：
Arulselvan P;Fard MT;Tan WS;Gothai S;Fakurazi S;Norhaizan ME;Kumar SS
通讯作者：
Kumar SS
影响因子：
5.4
作者：
Al-Attas, Ahmed A. M.;El-Shaer, Nagwa S.;Esmat, Ahmed
通讯作者：
Esmat, Ahmed
影响因子：
5.6
作者：
Attiq A;Jalil J;Husain K
通讯作者：
Husain K
影响因子：
12.3
作者：
Chandrasekharan NV;Simmons DL
通讯作者：
Simmons DL
影响因子：
9.3
作者：
Candelario-Jalil, Eduardo;de Oliveira, Antonio C. Pinheiro;Fiebich, Bernd L.
通讯作者：
Fiebich, Bernd L.