Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong 264117, People's Republic of China.
Key Laboratory of Marine Drugs, The Ministry of Education of China, Institute of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, Ocean University of China. Qingdao 266003, People's Republic of China.
Bioorg Chem. 2024 Apr;145:107194. doi: 10.1016/j.bioorg.2024.107194. Epub 2024 Feb 13.
Phytochemical investigation into the medium polar fraction of the ethanol extract of Euphorbia peplus led to the identification of 32 diterpenoids with five structural types. Compounds 1-5 and 7-11 are reported for the first time, while the configuration of 6,7-epoxy group of 6 was revised to be β-oriented. Compounds 1-5 feature a rare structural variation of the double bond at Δ migrating to Δ in the tigliane-type diterpenoid family. Biologically, compound 21 was found to be the only one to show moderate cytotoxic activity, associated with the presence of a benzoyloxy residue at C-16. Besides, compounds 4, 8, 12, 13, 16, and 19 show significant inhibitory activities against NO production induced by LPS in RAW264.7 macrophage cells, with IC values within 2-5 μM. Structure-activity relationship (SAR) analysis revealed that the ingenane-type diterpenoids have the best anti-inflammatory activity, and the esterification at 3-OH or 5-OH is crucial. Further biological researches demonstrated that 13, the predominant metabolite in this plant, exerts anti-inflammatory effects by blocking the activation of NF-κB and MAPK signaling pathways.
从Euphorbia peplus 的乙醇提取物的中等极性部分进行植物化学研究，鉴定出 32 种二萜类化合物，具有五种结构类型。化合物 1-5 和 7-11 是首次报道的，而 6 的 6,7-环氧基的构型被修订为β取向。化合物 1-5 在千里光型二萜类家族中表现出双键在 Δ 迁移到 Δ 的罕见结构变化。生物活性研究发现，21 号化合物是唯一具有中度细胞毒性活性的化合物，这与 C-16 处存在苯甲酰氧基残基有关。此外，化合物 4、8、12、13、16 和 19 对 LPS 诱导的 RAW264.7 巨噬细胞中 NO 产生具有显著的抑制作用，IC 值在 2-5 μM 范围内。构效关系（SAR）分析表明， ingenane 型二萜类化合物具有最佳的抗炎活性，3-OH 或 5-OH 的酯化作用至关重要。进一步的生物学研究表明，13 号化合物是该植物中的主要代谢产物，通过阻断 NF-κB 和 MAPK 信号通路的激活发挥抗炎作用。
