Muhammad Ishaq, Shams Ul Hassan Syed, Cheung Suet, Li Xiaoqing, Wang Rui, Zhang Wei-Dong, Yan Shi-Kai, Zhang Yan, Jin Hui-Zi
Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China; Department of Natural Product Chemistry, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
Department of Natural Product Chemistry, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
Fitoterapia. 2021 Jan;148:104800. doi: 10.1016/j.fitote.2020.104800. Epub 2020 Dec 8.
This report illustrated isolation and identification of 42 compounds comprising five (spicatainoids A-E) undescribed eremophilanolide type sesquiterpenoids and one undescribed nor-eremophilane (spicatainoid F) from Ligularia subspicata.. Among all the isolated new compounds, 4 is reported as the first enantiomeric form of novel eremophilanolide type sesquiterpenoid. Comprehensive analysis of HRESIMS, 1D/2D NMR, experimental circular dichroism (CD), calculated ECD analysis, and X-ray crystallographic (XRD) analysis validated the complete configuration and confirmation of these isolated compounds. All the isolated compounds were tested for the anti-inflammatory potential by measuring the amount of nitric oxide production. Among the tested compounds, 4 was the most effective with 90% NO-inhibition activity. Compounds 1, 2, 3, 9, 10 18, 29, 34, 35 exhibited moderate inhibitory effects against the production of NO, while other compounds displayed no activity even at the concentration of 50 μM. Additionally, compounds 1, 3 and 4 presented moderate anti-inflammatory activity by inhibiting the release of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in LPS-stimulated N9 cells. The IC values of compounds 1, 3 and 4 were calculated 39.6 ± 2.7, 42.5 ± 3.8 and 27.60 ± 1.9 μΜ.
本报告阐述了从狭苞橐吾中分离并鉴定出42种化合物，其中包括5种（spicatainoids A - E）未描述过的桉叶烷型倍半萜内酯和1种未描述过的降桉叶烷（spicatainoid F）。在所有分离得到的新化合物中，有4种被报道为新型桉叶烷型倍半萜内酯的第一种对映体形式。通过高分辨电喷雾电离质谱（HRESIMS）、一维/二维核磁共振（1D/2D NMR）、实验性圆二色光谱（CD）、计算性电子圆二色光谱（ECD）分析以及X射线晶体学（XRD）分析的综合研究，验证了这些分离得到的化合物的完整构型和结构。通过测量一氧化氮生成量，对所有分离得到的化合物进行了抗炎活性测试。在测试的化合物中，4号化合物最为有效，具有90%的一氧化氮抑制活性。化合物1、2、3、9、10、18、29、34、35对一氧化氮的生成表现出中等抑制作用，而其他化合物即使在50 μM浓度下也没有活性。此外，化合物1、3和4通过抑制脂多糖（LPS）刺激的N9细胞中促炎细胞因子（TNF-α、IL-1β和IL-6）的释放，呈现出中等程度的抗炎活性。化合物1、3和4的半数抑制浓度（IC）值分别计算为39.6 ± 2.7、42.5 ± 3.8和27.60 ± 1.9 μΜ。
