Study on the Deglycosylation Metabolism of Dioscin and Its Impact on the Proliferation of Human Colon Cancer Cells
10.14148/j.issn.1672-0482.2025.0494
- VernacularTitle:薯蓣皂苷的脱糖基代谢及其对人结肠癌细胞增殖的影响
- Author:
Guoqiang ZHANG
1
;
Zhenyao LU
;
Huan WANG
;
Bing HU
;
Hong CAI
Author Information
1. 徐州市中心医院药剂科,江苏 徐州 221002
- Publication Type:Journal Article
- Keywords:
dioscin;
deglycosylated metabolite;
colon cancer;
HPLC-MS/MS
- From:
Journal of Nanjing University of Traditional Chinese Medicine
2025;41(4):494-500
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the deglycosylation metabolism of dioscin in vivo and the changes of its anti-tumor activi-ty of its deglycosylated metabolites.METHODS An LC-MS/MS analysis method for simultaneous determination of dioscin and its deglycosylation metabolites was established to study the cumulative excretion amount of dioscin and its deglycosylated metabolites in rat feces after oral administration.To mimic its deglycosylation metabolism,HPLC method was applied to investigate the time-dependent changes in the prototype components and metabolites of dioscin after incubation in artificial gastric juice.Solid-phase extraction tech-nology was employed to isolate the product of dioscin following hydrolysis by artificial gastric juice.The cytotoxic effects of this product on human colon cancer cells HCT-116 were assessed using the CCK-8 assay across different hydrolysis time periods.Concurrently,the enzymatic activities of caspase-3 and caspase-9,along with the expression levels of cytochrome C,were measured to elucidate the impact of dioscin post-hydrolysis on the cytotoxicity against HCT-116 cells.RESULTS Dioscin and its series of deglycosylated me-tabolites were detected in rat feces,revealing no significant differences in the cumulative excretion amounts of Polyphyllin Ⅴ and Pro-genin Ⅱ.Dioscin was shown to generate a range of deglycosylated metabolites in artificial gastric juice.Furthermore,dioscin and its deglycosylated metabolites inhibited the proliferation of HCT-116 cells,induced morphological changes,and increased the enzymatic activities of caspase-3 and caspase-9,as well as cytochrome C expression.However,it was observed that the antitumor activity of the deglycosylated metabolites diminished with prolonged hydrolysis time.CONCLUSION The deglycosylation metabolism of dioscin sig-nificantly attenuates its inhibitory effect on the proliferation of HCT-116 cells.Suppressing the acid-mediated or gut microbiota-medi-ated deglycosylation metabolism may be a promising strategy to preserve its antitumor activity.
