Isolation, structural characterization, anti-tumor activity, and mechanisms of novel compounds from the roots of Aconitum pendulum Busch

Twelve compounds were isolated from the roots of Aconitum pendulum Busch, including a novel alkaloid (compound 1) and a new lignan (compound 2), along with ten known compounds. Activity studies demonstrated that compound 2 exhibited the most significant inhibitory effect on two types of tumor cells, HepG2 and HGC-27, with IC₅₀ values of 6.77 ± 0.34 μM and 2.54 ± 0.16 μM, respectively, surpassing the positive control, 5-fluorouracil. Mechanistic studies indicated that compound 2 exerted anti-tumor effects through multiple pathways, including the inhibition of cell migration, induction of apoptosis, and suppression of colony formation. Network pharmacological analyses suggested that compound 2 exerted multi-targeted anti-tumor effects by modulating various signaling pathways, including HIF-1α and NF-κB. Furthermore, Western blot experiments confirmed that this compound could downregulate HIF-1α expression in a concentration-dependent manner.