Diverse alkaloids from the aerial parts of Aconitum carmichaelii and antiproliferative activity of costemline via inhibiting SIRT1/ROCK1/P-STAT3 pathways

Six undescribed alkaloids together with 15 known alkaloids were isolated from the aerial parts of Aconitum carmichaelii. Their structures were elucidated extensively by NMR and HRESIMS spectroscopy. The absolute configurations of N-formyllaurotetanine, and the known compounds glaucine-beta-N-oxide and glaucine-alpha-N-oxide were established by electronic circular dichroism (ECD) spectra. Notably, it was the discovery of rare indole alkaloids from the genus Aconitum, and biosynthetic pathway of compounds 1 and 6 was deduced. Evaluation of the antiproliferative activity of these alkaloids demonstrated that costemline exhibited significant antiproliferation effects against HCT116, SKOV3, and A549 cells with IC50 values of 5.6, 14.2, and 6.8 mu M, respectively. Costemline could also inhibit the cell invasion activity of HCT116 cells. Mechanistic studies in HCT116 cells suggested that the antiproliferative activity of costemline was attributable to SIRT1/ROCK1/PSTAT3 pathways regulation. This study revealed the potential for developing and utilizing the aerial parts of Aconitum carmichaelii.

Automated summary

Six new alkaloids and 15 known alkaloids were isolated from the aerial parts of Aconitum carmichaelii. The structures were determined using NMR and HRESIMS spectroscopy, and the absolute configurations of some compounds were established using ECD spectra. The discovery of rare indole alkaloids from the Aconitum genus was highlighted, and the biosynthetic pathway of two compounds was deduced. The alkaloid costemline demonstrated significant antiproliferative effects and inhibition of cell invasion in various cancer cell lines, potentially through regulation of the SIRT1/ROCK1/PSTAT3 pathways.