Anemoside B4 regulates fatty acid metabolism reprogramming in mice with colitis-associated cancer.
10.19540/j.cnki.cjcmm.20221122.402
- Author:
Xin YANG
1
;
Jing JIA
1
;
Xin-Xu XIE
1
;
Meng-Qiang WAN
1
;
Yu-Lin FENG
1
;
Ying-Ying LUO
1
;
Hui OUYANG
1
;
Jun YU
2
Author Information
1. Chinese Medicine Solid Preparations National Engineering Research Center for Manufacturing Technology,Jiangxi University of Chinese Medicine Nanchang 330006, China.
2. Lewis Katz School of Medicine, Temple University Philadelphia 19140, USA.
- Publication Type:Journal Article
- Keywords:
anemoside B4;
colitis-associated cancer;
fatty acid de novo synthesis;
fatty acid β-oxidation
- MeSH:
Mice;
Animals;
Sterol Regulatory Element Binding Protein 1;
Colitis-Associated Neoplasms;
PPAR alpha/genetics*;
Colonic Neoplasms/genetics*;
Colon;
Azoxymethane;
RNA, Messenger;
Dextran Sulfate;
Colitis/drug therapy*;
Mice, Inbred C57BL;
Disease Models, Animal
- From:
China Journal of Chinese Materia Medica
2023;48(9):2325-2333
- CountryChina
- Language:Chinese
-
Abstract:
The study aimed to investigate the effect of anemoside B4(B4) on fatty acid metabolism in mice with colitis-associated cancer(CAC). The CAC model was established by azoxymethane(AOM)/dextran sodium sulfate(DSS) in mice. Mice were randomly divided into a normal group, a model group, and low-, medium-, and high-dose anemoside B4 groups. After the experiment, the length of the mouse colon and the size of the tumor were measured, and the pathological alterations in the mouse colon were observed using hematoxylin-eosin(HE) staining. The slices of the colon tumor were obtained for spatial metabolome analysis to analyze the distribution of fatty acid metabolism-related substances in the tumor. The mRNA levels of SREBP-1, FAS, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 were determined by real-time quantitative PCR(RT-qPCR). The results revealed that the model group showed decreased body weight(P<0.05) and colon length(P<0.001), increased number of tumors, and increased pathological score(P<0.01). Spatial metabolome analysis revealed that the content of fatty acids and their derivatives, carnitine, and phospholipid in the colon tumor was increased. RT-qPCR results indicated that fatty acid de novo synthesis and β-oxidation-related genes, such as SREBP-1, FASN, ACCα, SCD-1, ACOX, UCP-2, and CPT-1 mRNA expression levels increased considerably(P<0.05, P<0.001). After anemoside B4 administration, the colon length increased(P<0.01), and the number of tumors decreased in the high-dose anemoside B4 group(P<0.05). Additionally, spatial metabolome analysis showed that anemoside B4 could decrease the content of fatty acids and their derivatives, carnitine, and phospholipids in colon tumors. Meanwhile, anemoside B4 could also down-regulate the expression of FASN, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 in the colon(P<0.05, P<0.01, P<0.001). The findings of this study show that anemoside B4 may inhibit CAC via regulating fatty acid metabolism reprogramming.
