Kamaonensine A-G: Lycaconitine-type C19-diterpenoid alkaloids with anti-inflammatory activities from Delphinium kamaonense Huth

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 C19-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 C19-diterpenoid alkaloids had significant anti-inflammatory inhibitory activities, with kamaonensine E being the most potent (0.9 & PLUSMN; 0.2 & mu;M) stronger than positive (9.0 & PLUSMN; 1.3 & mu;M). In the network pharmacology studies, binding three key targets mitogenactivated protein kinase 8 (MAPK8), mitogen-activated protein kinase 14 (MAPK14), and heat shock protein HSP 90-alpha (HSP90 & alpha;), 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 C19-diterpenoid alkaloids.

Automated summary

This study isolated seven undescribed compounds with medicinal and anti-inflammatory activities from Delphinium kamaonense. In vitro assays showed significant inhibitory effects on nitric oxide, indicating potential anti-inflammatory properties. The mechanism of action may be related to the MAPK signaling pathway. Molecular docking results revealed two promising pharmacophores for the lycaconitine-type C19-diterpenoid alkaloids, namely the uncommon amides and methylenedioxy groups.