State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Science, Guangxi Normal University, Guilin, Guangxi, People's Republic of China.
College of Pharmacy, Natural Products Research Institute, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.
Fitoterapia. 2020 Apr;142:104486. doi: 10.1016/j.fitote.2020.104486. Epub 2020 Jan 24.
Inflammation is a very common and important basic pathological process. There is still a great need for the isolation of effective anti-inflammatory agents from plants. In this paper, five new isobutylamides, zanthoxylumamides E-I (1-5), and four known isobutylamides (6-9) were isolated from Zanthoxylum nitidum var. tomentosum (Rutaceae). Chiral resolution of seven racemic isobutylamides (1-4 and 6-8) was successfully performed, and the absolute configurations of two stereoisomers of 1-4 were validated by ECD and NMR. The obtained isobutylamides were evaluated in vitro anti-inflammatory activity with the lipopolysaccharide (LPS)-stimulated production of nitric oxide (NO) in murine macrophage RAW264.7 cells. Compound 8 exhibited significant inhibition of LPS-induced NO production. The underlying molecular mechanisms of the anti-inflammatory activity of 8 revealed that it suppressed the NO production through the modulation of myeloid differentiation factor 88 (MyD88) and interferon regulatory factor 3 (IRF3) signaling pathways.
炎症是一种非常常见和重要的基本病理过程。仍然需要从植物中分离出有效的抗炎剂。本文从花椒(Zanthoxylum nitidum var. tomentosum) (Rutaceae)中分离得到了 5 个新的异丁酰胺，即花椒酰胺 E-I(1-5)，和 4 个已知的异丁酰胺(6-9)。成功地对 7 个外消旋异丁酰胺(1-4 和 6-8)进行了手性拆分，并通过 ECD 和 NMR 验证了 1-4 的两个立体异构体的绝对构型。用脂多糖(LPS)刺激的鼠巨噬细胞 RAW264.7 细胞中一氧化氮(NO)的产生，评估了获得的异丁酰胺的体外抗炎活性。化合物 8 对 LPS 诱导的 NO 产生具有显著的抑制作用。8 抗炎活性的潜在分子机制表明，它通过调节髓样分化因子 88(MyD88)和干扰素调节因子 3(IRF3)信号通路来抑制 NO 的产生。
