COX-2, a key enzyme that catalyzed the rate-limiting steps in the conversion of arachidonic acid to prostaglandins, played a pivotal role in the inflammatory process. Different from other family members, COX-2 was barely detectable in normal physiological conditions and highly inducible during the acute inflammatory response of human bodies to injuries or infections. Therefore, the therapeutic utilization of selective COX-2 inhibitors has already been considered as an effective approach for the treatment of inflammation with diminished side effects. Currently, both traditional and newer NSAIDs are the commonly prescribed medications that treat inflammatory diseases by targeting COX-2. However, due to the cardiovascular side-effects of the NSAIDs, finding reasonable alternatives for these frequently prescribed medicines are a hot spot in medicinal chemistry research. Naturallyoccurring compounds have been reported to inhibit COX-2, thereby possessing beneficial effects against inflammation and certain cell injury. The review mainly concentrated on recently identified natural products and derivatives as COX-2 inhibitors, the characteristics of their structural core scaffolds, their anti-inflammatory effects, molecular mechanisms for enzymatic inhibition, and related structure-activity relationships. According to the structural features, the natural COX-2 inhibitors were mainly divided into the following categories: natural phenols, flavonoids, stilbenes, terpenoids, quinones, and alkaloids. Apart from the anti-inflammatory activities, a few dietary COX-2 inhibitors from nature origin also exhibited chemopreventive effects by targeting COX-2-mediated carcinogenesis. The utilization of these natural remedies in future cancer prevention was also discussed. In all, the survey on the characterized COX-2 inhibitors from natural sources paves the way for the further development of more potent and selective COX-2 inhibitors in the future.

COX-2 是催化花生四烯酸转化为前列腺素的限速步骤的关键酶，在炎症过程中发挥了关键作用。与其他家族成员不同，COX-2 在正常生理条件下几乎检测不到，在人体对损伤或感染的急性炎症反应中具有高度诱导性。因此，选择性 COX-2 抑制剂的治疗应用已被认为是治疗炎症且副作用减少的有效方法。目前，传统和新型 NSAID 都是通过靶向 COX-2 治疗炎症性疾病的常用处方药。然而，由于 NSAIDs 的心血管副作用，为这些常用处方药寻找合理的替代品是药物化学研究的热点。据报道，天然存在的化合物可抑制 COX-2，从而对炎症和某些细胞损伤具有有益作用。综述主要集中在最近发现的作为 COX-2 抑制剂的天然产物和衍生物、其结构核心支架的特征、它们的抗炎作用、酶抑制的分子机制以及相关的构效关系。根据结构特点，天然COX-2抑制剂主要分为以下几类：天然酚类、黄酮类、芪类、萜类、醌类和生物碱类。除了抗炎作用，一些天然来源的膳食 COX-2 抑制剂也通过靶向 COX-2 介导的致癌作用而表现出化学预防作用。还讨论了这些自然疗法在未来癌症预防中的应用。总之，对天然来源的特征性 COX-2 抑制剂的调查为未来进一步开发更有效和选择性的 COX-2 抑制剂铺平了道路。