MS/MS-based molecular networking discovery of sesquiterpenes from Carpesium abrotanoides L. with their cytotoxic and acetylcholinesterase inhibitory activity.

Employing an MS/MS-based molecular networking-guided strategy, three new eudesmane-type sesquiterpenes (1-3) and one undescribed pseudoguaianolide sesquiterpene (8), along with four known eudesmane-type sesquiterpene lactones (4-7) were extracted and purified from the herbs of Carpesium abrotanoides L. Structural elucidation encompassed comprehensive spectroscopic analysis, NMR calculations, DP4+ analysis, and ECD calculations. The cytotoxicity activity of all isolates was evaluated against two human hepatoma carcinoma cells (HepG2 and Hep3B) in vitro. It was demonstrated that compounds 2 and 4 showed moderate cytotoxic against HepG2 and Hep3B cells. Furthermore, all compounds were evaluated for their acetylcholinesterase (AChE) inhibitory activity. Particularly noteworthy is that, in comparison to the positive control, compound 1 demonstrated significant AChE inhibition with an inhibition rate of 77.86%. In addition, the inhibitory mechanism of compound 1 were investigated by in silico docking analyze and molecular dynamic simulation.

A highly oxidized germacranolide from elephantopus tomentosus inhibits the growth of hepatocellular carcinoma cells by targeting EGFR in vitro and in vivo.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with high mortality and poor prognosis. WBDC-1 is a novel highly oxidized germacranolide from the Elephantopus tomentosus in our previous work, which has excellent anti-HCC activity, but the detailed mechanism is still unclear. In this study, we found that WBDC-1 was able to inhibit the proliferation and colony formation of Hep3B and HepG2 cells, as well as the cell migration ability and EMT. In addition, WBDC-1 showed no obvious toxicity to normal liver epithelial cells L-02. The potential targets of WBDC-1 were predicted by network pharmacology, and the following verified experiments showed that WBDC-1 exerted anti-HCC effect by targeting EGFR. Mechanismly, subsequent biological analysis showed that WBDC-1 can inhibit EGFR and its downstream RAS/RAF/MEK/ERK and PI3K/AKT signaling pathways. Overexpression of EGFR reversed the anticancer properties of WBDC-1. Consistent with in vitro experiments, WBDC-1 was able to inhibit tumor growth and was non-toxic in xenograft tumor models. In summary, this study revealed a potential tumor suppressive mechanism of WBDC-1 and provided a novel strategy for HCC treatment. It also laid a foundation for further research on the anti-tumor effect of highly oxidized germacranolides.