Colorectal carcinoma (CRC) is a kind of malignant
tumor closely related to
ulcerative colitis.
Xanthone derivatives are one of the most promising therapeutic drugs which have been used in phase I/II clinical trials for
cancer therapy. Our previous study indicated that the aerial parts of Gentianella acuta Michx. Hulten (GA) was rich in
xanthones and showed a good
therapeutic effect on
ulcerative colitis in mice, suggesting that GA
xanthones might have some therapeutic or ameliorative effects on CRC. However, no relevant study has been reported. This study aims to find the effective substances of GA inhibiting CRC and clarify their mechanism.
Solvent extraction, column chromatographic separation, and LC-MS analysis were used to characterize the 70% EtOH extract of GA and track
xanthones abundant fraction XF. MTT assay was carried out to clarify the activity of GA fractions; the result showed XF to be the main active fraction. LC-MS analysis was executed to characterize XF, 38
xanthones were identified. Network pharmacology prediction, in vitro activity screening, and molecular docking assay were combined to predict the potential mechanism; the PI3K/Akt/mTOR signaling pathway was found to be most important. Western blot assay on the main active
xanthones 1,3,5-trihydroxyxanthone (16),
1,3,5,8-tetrahydroxyxanthone (17), 1,5,8-trihydroxy-3-methoxyxanthone (18), and
1,7-dihydroxy-3,8-dimethoxyxanthone (19) was used to verify the above prediction; these
xanthones were found to inhibit the PI3K/Akt/mTOR signaling pathway, and 17 played a significant role among them through Western blot assay using PI3K/AKT/mTOR agonist
IGF-1. In conclusion, this study demonstrated that GA
xanthones were effective compounds of GA inhibiting CRC by regulating PI3K/Akt/mTOR signaling pathway transduction, at least. Importantly,
1,3,5,8-tetrahydroxyxanthone (17), the most abundant active
xanthone in GA, might be a candidate
drug for CRC.