Non-steroidal anti-inflammatory drugs (NSAIDs) relieve inflammation by suppressing prostaglandin E₂/cyclooxygenase 2 (PGE₂/COX-2) with cardiovascular and gastrointestinal bleeding risk. Theoretically, suppressing PGE₂ through inhibiting the terminal synthase microsomal prostaglandin E₂ synthase-1 (mPGES-1) instead of upstream COX-2 is ideal for inflammation. Here, (9S,13R)−12-oxo-phytodienoic acid (AA-24) extracted from Artemisia anomala was first screened as an anti-inflammatory candidate and decreased inducible nitric oxide synthase (iNOS), nitric oxide (NO), mPGES-1, and PGE₂ without affecting COX-1/2, thromboxane A₂ (TXA₂) and prostaglandin I₂ (PGI₂). Besides, AA-24 suppressed the differentiation of M0 macrophages to M1 phenotype but enhanced it to M2 phenotype, blocked the activation of NF-κB pathway, and increased the activation of Nrf2 and heme oxygenase-1 (HO-1). Moreover, AA-24 selectively inhibited mPGES-1 and reduced inflamed paw edema in carrageenan-induced mice. In conclusion, AA-24 attenuates inflammation by inhibiting mPGES-1 and modulating macrophage polarization via the NF-κB and Nrf2/HO-1 pathways and could be a promising candidate for developing anti-inflammatory drugs.

非甾体抗炎药 (NSAIDs) 通过抑制具有心血管和胃肠道出血风险的前列腺素 E ₂ /环氧合酶 2 (PGE _{2 /COX-2) 来缓解炎症。}理论上，通过抑制末端合成酶微粒体前列腺素 E ₂合成酶-1 (mPGES-1) 而不是上游 COX-2 来抑制 PGE _{2是炎症的理想选择。}在这里，从异常蒿中提取的(9 S ,13 R )-12-氧代植物二烯酸 (AA-24)首次被筛选为抗炎候选物，并降低诱导型一氧化氮合酶 (iNOS)、一氧化氮 (NO)、 mPGES-1 和 PGE ₂不影响 COX-1/2、血栓素 A₂ (TXA ₂ ) 和前列腺素 I ₂ (PGI ₂ )。此外，AA-24 抑制 M0 巨噬细胞向 M1 表型的分化，但增强其向 M2 表型的分化，阻断 NF-κB 通路的激活，并增加 Nrf2 和血红素加氧酶-1 (HO-1) 的激活。此外，AA-24 选择性地抑制 mPGES-1 并减少角叉菜胶诱导的小鼠发炎的爪子水肿。总之，AA-24 通过抑制 mPGES-1 和通过 NF-κB 和 Nrf2/HO-1 途径调节巨噬细胞极化来减轻炎症，并且可能是开发抗炎药物的有希望的候选者。