State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao, PR China; NMPA Key Laboratory for Quality Evaluation of TCM, and Guangdong Provincial Engineering Research Center for Modernization of TCM, College of Pharmacy, Jinan University, Guangzhou, 510632, PR China.
State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao, PR China.
Phytochemistry. 2023 Dec;216:113869. doi: 10.1016/j.phytochem.2023.113869. Epub 2023 Sep 20.
Twelve undescribed limonoids, meliazedarines J-U (1-12), along with a known one, were isolated from the roots of Melia azedarach. Their structures were elucidated by extensive spectroscopic investigations, X-ray diffraction analyses, and ECD calculations. Compounds 1-8 were identified as ring intact limonoids, while compounds 9-12 were established as ring C-seco ones. The anti-inflammatory potential of compounds 1-4, 6, 8, 9, and 11-13 was evaluated on macrophages. Compounds 1, 3, 4, 6, and 9 significantly suppressed nitric oxide production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages, among them compound 3 showed the best inhibitory effect with an IC value of 7.07 ± 0.48 μΜ. Furthermore, compound 3 effectively reduced interleukin-1β secretion in LPS plus nigericin-induced THP-1 macrophages by inhibiting NLRP3 inflammasome activation. The results strongly suggested that limonoids from the roots of M. azedarach might be candidates for treating inflammation-related diseases.
从苦楝树的根部分离得到了 12 种未描述的柠檬苦素类化合物，包括 meliazedarines J-U（1-12），以及一种已知的化合物。通过广泛的光谱研究、X 射线衍射分析和 ECD 计算确定了它们的结构。化合物 1-8 被鉴定为环完整的柠檬苦素类化合物，而化合物 9-12 则被确定为环 C-断裂的柠檬苦素类化合物。对化合物 1-4、6、8、9 和 11-13 的抗炎潜力在巨噬细胞上进行了评估。化合物 1、3、4、6 和 9 显著抑制了脂多糖（LPS）诱导的 RAW 264.7 巨噬细胞中一氧化氮的产生，其中化合物 3 表现出最好的抑制效果，IC 值为 7.07±0.48 μM。此外，化合物 3 通过抑制 NLRP3 炎性体的激活，有效减少了 LPS 加 Nigericin 诱导的 THP-1 巨噬细胞中白细胞介素-1β的分泌。结果强烈表明，苦楝树根部的柠檬苦素类化合物可能是治疗炎症相关疾病的候选药物。
