School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, PR China.
School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, PR China.
Phytochemistry. 2023 Nov;215:113822. doi: 10.1016/j.phytochem.2023.113822. Epub 2023 Aug 12.
Delphinium kamaonense Huth is a sort of folkloric plant resource which is cultivated and planted with great ornamental and medicinal values. In this work, seven undescribed lycaconitine-type C-diterpenoid alkaloids, especially a rare skeleton with -CH=N and N-oxide moieties, along with ten known compounds, were isolated from D. kamaonense, of which the structures were determined by various spectroscopic data, combined with calculated electronic circular dichroism (ECD) and single-crystal X-ray diffraction analysis. In vitro nitric oxide inhibitory activities assay of these compounds indicated that lycaconitine-type C-diterpenoid alkaloids had significant anti-inflammatory inhibitory activities, with kamaonensine E being the most potent (0.9 ± 0.2 μM) stronger than positive (9.0 ± 1.3 μM). In the network pharmacology studies, binding three key targets mitogen-activated protein kinase 8 (MAPK8), mitogen-activated protein kinase 14 (MAPK14), and heat shock protein HSP 90-alpha (HSP90α), the anti-inflammatory mechanism might be related to MAPK signaling pathways. Furthermore, the molecular docking results revealed that the uncommon amides and methylenedioxy groups might be the most two promising pharmacophores for lycaconitine-type C-diterpenoid alkaloids.
宽乌头是一种民间药用植物资源，具有很大的观赏和药用价值。本工作从宽乌头中分离得到 7 个未见报道的新的裂环烯醚萜类 C-二萜生物碱，特别是一个罕见的骨架，具有-CH=N 和 N-氧化物部分，以及 10 个已知化合物，通过各种光谱数据，结合计算电子圆二色谱（ECD）和单晶 X 射线衍射分析确定了它们的结构。这些化合物的体外一氧化氮抑制活性测定表明，裂环烯醚萜类 C-二萜生物碱具有显著的抗炎抑制活性，其中宽乌头宁 E 是最有效的（0.9±0.2μM），比阳性对照（9.0±1.3μM）更强。在网络药理学研究中，通过结合三个关键靶点丝裂原活化蛋白激酶 8（MAPK8）、丝裂原活化蛋白激酶 14（MAPK14）和热休克蛋白 HSP 90-α（HSP90α），抗炎机制可能与 MAPK 信号通路有关。此外，分子对接结果表明，不常见的酰胺和亚甲二氧基可能是裂环烯醚萜类 C-二萜生物碱最有前途的两个药效团。
