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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. Full article

As a Mongolian native medicine and Ewenki folk medicinal plant, Gentianella acuta has been widely used for the treatment of diarrhea, hepatitis, arrhythmia, and coronary heart disease. In the course of investigating efficacy compounds to treat diarrhea using a mouse isolated intestine tissue model, we found 70% EtOH extract of G. acuta whole plants had an inhibitory effect on intestine contraction tension. Here, nineteen constituents, including five new compounds, named as gentiiridosides A (1), B (2), gentilignanoside A (3), (1R)-2,2,3-trimethyl-4-hydroxymethylcyclopent-3-ene-1-methyl-O-β-d-glucopyranoside (4), and (3Z)-3-hexene-1,5-diol 1-O-α-l-arabinopyranosyl(1→6)-β-d-glucopyranoside (5) were obtained from it. The structures of them were elucidated by chemical and spectroscopic methods. Furthermore, the inhibitory effects on motility of mouse isolated intestine tissue of the above mentioned compounds and other thirteen iridoid- and secoiridoid-type monoterpenes (7–10, 13–16, 18, 19, 21, 22, and 25) previously obtained in the plant were analyzed. As results, new compound 5, some secoiridoid-type monoterpenes 7, 10, 12–14, 16, and 17, as well as 7-O-9′-type lignans 31 and 32 displayed significant inhibitory effect on contraction tension at 40 μM. Full article