Bletilla striata polysaccharide improves toxic and side effects induced by 5-FU: an untargeted metabolomics study.
10.19540/j.cnki.cjcmm.20230413.705
- Author:
Jiang-Tao ZHANG
1
;
Peng LIU
2
;
Wen-Long WANG
2
;
Xin-Xu XIE
2
;
Tao-Hong HE
2
;
Ya-Ru CUI
3
;
Jun YU
4
Author Information
1. Centre for Translational Medicine, Jiangxi University of Chinese Medicine Nanchang 330006, China Jiangxi Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Vascular Remodeling Diseases,Jiangxi University of Chinese Medicine Nanchang 330006, China.
2. National Pharmaceutical Engineering Center for Solid Preparation of Chinese Herb Medicine, Jiangxi University of Chinese Medicine Nanchang 330006, China.
3. Jiangxi Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Vascular Remodeling Diseases,Jiangxi University of Chinese Medicine Nanchang 330006, China National Pharmaceutical Engineering Center for Solid Preparation of Chinese Herb Medicine, Jiangxi University of Chinese Medicine Nanchang 330006, China.
4. Lewis Katz School of Medicine, Temple University Philadelphia PA19140, USA.
- Publication Type:Randomized Controlled Trial, Veterinary
- Keywords:
Bletilla striata polysaccharide;
chemotherapy-induced diarrhea;
chemotherapy-induced myelosuppression;
untargeted metabolomics
- MeSH:
Animals;
Male;
Mice;
Colonic Neoplasms/drug therapy*;
Diarrhea;
Fluorouracil/adverse effects*;
Hormones;
Metabolomics;
Mice, Inbred BALB C;
Polysaccharides/pharmacology*
- From:
China Journal of Chinese Materia Medica
2023;48(13):3612-3622
- CountryChina
- Language:Chinese
-
Abstract:
This study aimed to analyze the effect of Bletilla striata polysaccharide(BSP) on endogenous metabolites in serum of tumor-bearing mice treated with 5-fluorouracil(5-FU) by untargeted metabolomics techniques and explore the mechanism of BSP in alleviating the toxic and side effects induced by 5-FU. Male BALB/C mice were randomly divided into a normal group, a model group, a 5-FU group, and a 5-FU + BSP group, with eight mice in each group. Mouse colon cancer cells(CT26) were transplanted into the mice except for those in the normal group to construct the tumor-bearing mouse model by subcutaneous injection, and 5-FU chemotherapy and BSP treatment were carried out from the second day of modeling. The changes in body weight, diarrhea, and white blood cell count in the peripheral blood were recorded. The mice were sacrificed and sampled when the tumor weight of mice in the model group reached approximately 1 g. TUNEL staining was used to detect the cell apoptosis in the small intestine of each group. The proportions of hematopoietic stem cells and myeloid progenitor cells in bone marrow were measured by flow cytometry. Five serum samples were selected randomly from each group for untargeted metabolomics analysis. The results showed that BSP was not effective in inhibiting colon cancer in mice, but diarrhea, leukopenia, and weight loss caused by 5-FU chemotherapy were significantly improved after BSP intervention. In addition, apoptotic cells decreased in the small intestinal tissues and the percentages of hematopoietic stem cells and myeloid progenitor cells in bone marrow were significantly higher after BSP treatment. Metabolomics results showed that the toxic and side effects of 5-FU resulted in significant decrease in 29 metabolites and significant increase in 22 metabolites in mouse serum. Among them, 19 disordered metabolites showed a return to normal levels in the 5-FU+BSP group. The results of pathway enrichment indicated that metabolic pathways mainly involved pyrimidine metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis. Therefore, BSP may ameliorate the toxic and side effects of 5-FU in the intestinal tract and bone marrow presumably by regulating nucleotide synthesis, inflammatory damage, and hormone production.
