Unveiling the Anticancer Mechanism of Echinops davuricus: Isolation and Evaluation of AKR1B10 Inhibitors

Abstract

Five compounds (1–5), one long‐chain fatty acid (1), two thiophenes (2 and 3), one alkaloid (4), and one phenyl ester (5), were isolated from the aerial part of Echinops davuricus. The structures of the products were established by performing detailed nuclear magnetic resonance (NMR) analysis, and the structure of compound 1 was determined via high‐resolution electrospray ionization mass spectrometry (HRESIMS) and NMR. Compounds 1, 4, and 5 were isolated from Echinops davuricus for the first time. Based on network pharmacology methods, AKR1B10 was selected as a key anticancer target. Compounds 1 and 5 exhibited significant AKR1B10 inhibitory activities, with IC50 values of 156.0±1.00 and 146.2±1.50 nM, respectively, with epalrestat used as the positive control (81.09±0.61 nM). Additionally, the interactions between the active compounds and AKR1B10 were evaluated via molecular docking. Ultimately, the GO and KEGG enrichment analysis indicated that the key signaling pathways associated with the active compounds may be related to the PI3K‐Akt, MAPK, apoptotic, cellular senescence, and TNF signaling pathways and the human diseases corresponding to the targets are cancer. Our study reveals for the first time the anticancer properties of Echinops davuricus and provides a comprehensive understanding of its application in traditional medicine.

A Review of the Phytochemistry and Biological Activities of Echinopsis Radix

“…In addition, our previous chemical and biological activity studies revealed that the important anti-cancer targets of Echinopsis Radix, especially the anti-liver cancer AKR1B10, by network pharmacology strategies. And for the first time, compounds 83 and 85 have been reported to have significant AKR1B10 inhibitory activity, which provides new ideas for later research on the hepatoprotective effect of Echinopsis Radix [26].…”

“…In addition to the chemical components reported above, Echinopsis Radix is also rich in many other components, such as triterpenes, steroids, benzothiophenes, and fatty acids [24][25][26]. The structures of other compounds (73-82) are presented in Figure 8.…”