Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, 133002, China.
Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, 133002, China.
Eur J Med Chem. 2024 Mar 5;267:116223. doi: 10.1016/j.ejmech.2024.116223. Epub 2024 Feb 7.
Acute lung injury (ALI) is a clinically high mortality disease, which has not yet been effectively treated. The development of anti-ALI drugs is imminent. ALI can be effectively treated by inhibiting the inflammatory cascade and reducing the inflammatory response in the lung. Forsythia suspense is a common Chinese herbal medicine with significant anti-inflammatory activity. Using forsythin as the parent, 27 Forsythin derivatives were designed and synthesized, and the anti-AIL activity of these compounds was evaluated. Among them, compound B5 has the best activity to inhibit the release of IL-6, and the inhibition rate reaches 91.79% at 25 μM, which was 7.5 times that of the parent forsythin. In addition, most of the compounds have no significant cytotoxicity in vitro. Further studies showed that compound B5 had a concentration-dependent inhibitory effect on NO, IL-6 and TNF-α. And the IC values of compound B5 for NO and IL-6 are 10.88 μM and 4.93 μM, respectively. We also found that B5 could significantly inhibit the expression of some immune-related cytotoxic factors, including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, B5 inhibits NF-κB/MAPK signaling pathway. In vivo experiments showed that B5 could alleviate lung inflammation in LPS-induced ALI mice and inhibit IL-6, TNF-α, COX-2 and iNOS. In summary, B5 has anti-inflammatory effects and alleviates ALI by regulating inflammatory mediators and inhibiting MAPK and NF-κB signaling pathways.
急性肺损伤（ALI）是一种临床死亡率较高的疾病，目前尚未得到有效治疗。开发抗 ALI 药物迫在眉睫。通过抑制炎症级联反应和减轻肺部炎症反应，可以有效治疗 ALI。连翘是一种具有显著抗炎活性的常用中草药。以连翘苷为母体，设计并合成了 27 种连翘苷衍生物，并评价了这些化合物的抗 ALI 活性。其中，化合物 B5 对抑制 IL-6 的释放活性最好，在 25 μM 时抑制率达到 91.79%，是母体连翘苷的 7.5 倍。此外，大多数化合物在体外无明显细胞毒性。进一步研究表明，化合物 B5 对 NO、IL-6 和 TNF-α 具有浓度依赖性抑制作用。化合物 B5 对 NO 和 IL-6 的 IC 值分别为 10.88 μM 和 4.93 μM。我们还发现 B5 可以显著抑制一些免疫相关细胞毒性因子的表达，包括诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）。此外，B5 抑制 NF-κB/MAPK 信号通路。体内实验表明，B5 可减轻 LPS 诱导的 ALI 小鼠肺炎症，并抑制 IL-6、TNF-α、COX-2 和 iNOS。综上所述，B5 具有抗炎作用，通过调节炎症介质和抑制 MAPK 和 NF-κB 信号通路缓解 ALI。
