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用天然产品对抗炎症之战

Raging the War Against Inflammation With Natural Products.

作者信息

Attiq Ali, Jalil Juriyati, Husain Khairana, Ahmad Waqas

机构信息

Drug and Herbal Research Centre, Faculty of Pharmacy, University Kebangsaan Malaysia, Kuala Lumpur, Malaysia.

School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor, Malaysia.

出版信息

Front Pharmacol. 2018 Sep 7;9:976. doi: 10.3389/fphar.2018.00976. eCollection 2018.

Abstract

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 PGE inhibitory activity, since it is anticipated that isolates with ability to inhibit COX-2 mediated PGE 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.

摘要

在过去几十年中,非甾体抗炎药(NSAIDs)是治疗包括类风湿性关节炎在内的多种炎症性疾病的首选药物。NSAIDs通过抑制环氧化酶发挥抗炎活性,该酶负责将花生四烯酸转化为前列腺素。同样,环氧化酶-2抑制剂(COX-2)选择性抑制COX-2酶,并产生显著的抗炎、镇痛和解热活性,而不会产生与COX-1相关的胃肠道和肾脏副作用。在过去二十年中,已经开发并批准了多种选择性COX-2抑制剂(COXIBs)用于各种炎症性疾病。然而,临床试验数据表明,长期使用COX-2抑制剂也与危及生命的心血管副作用有关,包括缺血性心力衰竭和心肌感染。在这种情况下,天然产物的次生代谢产物为新型抗炎化合物的开发带来了巨大希望。虽然大多数基于天然产物的化合物对COX-1表现出更高选择性。然而,数据表明,轻微的结构修饰有助于开发具有相当疗效和有限副作用的COX-2选择性次生代谢产物。这篇综述旨在突出陆地和海洋来源的次生代谢产物,它们具有显著的COX-2和COX-2介导的PGE抑制活性,因为预计能够抑制COX-2介导的PGE产生的分离物将有助于抑制炎症及其典型的体征和症状。此外,这篇综述还突出了潜在的先导化合物,包括小檗碱、贝壳杉烯酸、α-香附酮、姜黄素和莪术二醇,并借助构效关系(SAR)研究及其现状对其进行进一步开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4987/6137277/c2af8a8d6d4d/fphar-09-00976-g0001.jpg

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