Diterpenoids with anti-inflammatory activity from the lateral root of Aconitum carmichaelii debeaux

Five undescribed diterpenoids, including two ent-cleistanthane-type diterpenoids aconicleistanthanes A and B, a hetisine-type diterpenoid aconihetisine A, two aconitines-type diterpenoids aconicarmines A and B, and thirteen known diterpenoids alkaloids, were co-isolated from the lateral root of the Aconitum carmichaelii Debeaux (Ranunculaceae). Their structures were elucidated based on spectroscopic methods, and the absolute configurations were determined by X-ray diffraction and electronic circular dichroism (ECD) calculations. Among them, aconicleistanthanes A and B as ent-cleistanthane-type diterpenoid featuring a unique five-membered lactone D ring, is the first reported example of ent-cleistanthane-type diterpenoids in the Aconitum, which provided a new type of diterpene metabolites for Aconitum and enriched the chemical space of the plant of the Aconitum. In the bioassays, aconicleistanthane A significantly suppressed the production of pro-inflammatory mediators (IL-6, IL-1β and COX-2) and the protein expression of the enzyme iNOS at the concentration of 6.25 μM.