中国科学院昆明植物研究所知识管理系统

Aconitum species represent a large genus in the Ranunclaceae family. Statistically, there are more than 350 species of Aconitum all over the world, most of them are widely distributed in the northern temperate zone, of which 173 species are endemic to mainland China. About 73 species are used as folk medicines, which are commonly applied to treat various kinds of pains and rheumatic arthritis. Diterpenoid alkaloids are considered to be the main bioactive and toxic constituents. The significant structural complexity and pharmacological activities have attached the attention of phytochemists for a long time. As one of the most characteristic Tibetan folk medicine, A. flavum Hand.-Mazz, mainly distributed in Qinghai, Gansu and other northwest places in China, was commonly used for the treatment of traumatic injuries, rheumatic arthritis. This plant possesses abundant DAs, and the preliminary experiment demonstrated that the different parts of the plant possessed distinctly different types of DAs. In order to discover the structurally new and potentially bioactive DAs, further develop and apply the plant, we carried out investigations on the aerial parts and roots of A. flavum. On the basis of chromatographies over various materials and extensive spectroscopic methods, a total of 46 DAs including 12 new compounds, 1 new natural compound and 33 known compounds were isolated and identified from A. flavum. These isolated DAs covered aconitine-type, 7,17-seco-aconitine-type, franchetine-type, napelline-type and veatchine-type. It is worthy to note that this study found the second spiro-cyclic 7,17-seco-type C19-DA which possessed a rearranged hexatomic B ring formed by the C(8)-C(10) linkage; a novel 7,17-seco-type C19-DA with exiguous five-ring system; the second aconitine-type DA possessed a -CN moiety and two rare aconitine-type DAs which possessed a N-acetaldehyde unit. Meanwhile, we isolated and identified 7 known compounds from the roots, the majority of them were napelline-type C20-DAs. With regard to pharmacological activities, compound 16 (30 μM) exhibited 64.5% inhibitory rate on Cav3.1 T-type calcium channel (TTCC); compound 13 showed  potential inhibitory effects against four human tumor cell lines HL-60, A-549, SMMC-7721, MCF-7 with IC50 value as 16.88, 33.11, 23.97, 24.21 μM in vitro; Compounds 4, 9, 13, 14, 15, and 19 showed potential inhibitory effects on NO production ranging from 20% to 32% at 50 μM, and new compounds 1–9 showed potential inhibitory effects on AChE. Generally, various types of DAs from different parts of A. flavum were isolated and characterized. As a result, most constituents of aerial parts were C19-DAs and the majority compounds of roots were napelline-type C20-DAs. Additionally, some of them were studied on bioassays at the cellular level. This study may work in enriching the phytochemical and pharmacological research on medicinal plants from the Aconitum genus and provide scientific evidences