Interaction Between Bruceoside B and Intestinal Flora and Its Inhibitory Effect on Human Lung Cancer A549 Cells
10.13422/j.cnki.syfjx.20240767
- VernacularTitle:鸦胆子苷B与肠道菌群相互作用及对人肺癌A549细胞的抑制作用
- Author:
Lingyu SHI
1
;
Wenmin WANG
1
;
Yulin FENG
1
;
Shilin YANG
1
;
Yang WAN
1
;
Daofeng CHEN
2
;
Quan WEN
1
Author Information
1. Jiangxi University of Chinese Medicine，Nanchang 330006，China
2. School of Pharmacy，Fudan University，Shanghai 201203，China
- Publication Type:Journal Article
- Keywords:
Brucea javanica;
bruceoside B;
brusatol;
intestinal flora;
metabolic transformation;
human lung cancer A549 cells;
non-small cell lung cancer（NSCLC）;
16S rRNA high-throughput sequencing
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(13):160-166
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the interaction between bruceoside B and gut microbiota and the inhibitory activity of its metabolites on human lung cancer A549 cells， and to explore the value of bruceoside B in the treatment of non-small cell lung cancer（NSCLC）. MethodBruceoside B was co-incubated with the human gut microbiota under anoxic conditions in vitro， and ultra high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used to analyze the metabolic transformation products. Cell counting kit-8（CCK-8） assay was performed to determine the effects of bruceoside B and its metabolites on the proliferation of human lung cancer A549 cells and the half inhibitory concentration（IC50） was calculated. Five healthy male rats were gavaged with bruceoside B（2 mg·kg-1） for 7 days after adaptive feeding. The feces of rats were collected before and after administration. 16S rRNA sequencing was used to assess gut microbiota. ResultBruceoside B was mainly metabolized to brusatol by human gut microbiota， the IC50 of bruceoside B and the conversion product to A549 cells were 1 755.50， 19.57 μmol·L-1， respectively， and the conversion product had a better activity at inhibiting A549 cells proliferation than bruceoside B. Additionally， The results of intestinal flora analysis showed no significant differences in α diversity and β diversity of gut microbiota after administration. In terms of species abundance， at the phylum level， bruceoside B decreased the relative abundance of Actinobacteriota and Proteobacteria， increased the relative abundance of Firmicutes， Patescibacteria and Cyanobacteria. At the genus level， bruceoside B decreased the relative abundance of Staphylococcus， Aerococcus and Psychrobacter， increased the relative abundance of Romboutsia， Lactobacillus， Clostridium sensu stricto 1， Norank-f-norank-o-Clostridia-UCG-014， Turicibacter， Allobaculum and Candidatus Saccharimonas. The results of functional prediction showed that the gut microbiota functional compositions were relatively stable. ConclusionBruceoside B can be deglycosylated by intestinal flora and converted into brusatol， with a significant increase in antitumor activity. The administration of bruceoside B will not cause significant changes in the structure and function of the intestinal flora， resulting in intestinal microecological balance disorders， and the administration appears to be beneficial to the intestinal flora of NSCLC patients.
