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Microarray Expression Profiling and Raman Spectroscopy Reveal Anti-Fatty Liver Action of Berberine in a Diet-Induced Larval Zebrafish Model
Chen, Bo1,2; Zheng, Yang-Min1,2,3; Zhang, Miao-Qing1,2,4,5; Han, Ying6; Zhang, Jing-Pu1,2; Hu, Chang-Qin6
2020-01-08
Source PublicationFRONTIERS IN PHARMACOLOGY
ISSN1663-9812
Volume10Pages:15
AbstractBackground: The prevalence of non-alcohol fatty liver disease (NAFLD) is increasing in children and adolescents who are mostly resulted from overfeeding. Previous studies demonstrate that berberine (BBR), a compound derived from plant, has beneficial effects on NAFLD in adults but poorly understood in the pediatric population. This study employed a larval zebrafish model to mimic the therapeutic effects of BBR in the pediatric population and the mechanisms underlying its hepatoprotection. Methods: High-cholesterol diet (HCD)-fed zebrafish exposed to BBR at doses of 0, 1, 5, and 25 mu M. After the larvae were treated with BBR for 10 days, its effect on hepatic steatosis was evaluated. We introduced Raman imaging and three-dimensional (3D) molecular imaging to detect changes in the biochemical composition and reactive oxygen species (ROS) levels of zebrafish liver. Gene expression microarray was performed to identify differentially expressed genes (DEGs) followed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and functional category analysis. Results: BBR (5 and 25 mu M) administration prevented HCD-induced liver lipid accumulation in larval zebrafish. The result was further confirmed by the pathological observation. Raman mapping indicated that the biochemical composition in the liver of BBR-treated group shifted to the control. The quantitative analysis of 3D imaging showed that the ROS level was significantly decreased in the liver of BBR-treated larvae. In the livers of the BBR group, we found 468 DEGs, including 172 genes with upregulated expression and 296 genes with downregulated expression. Besides, GO enrichment, KEGG pathway, and functional category analysis showed that various processes related to glucolipid metabolism, immune response, DNA damage and repair, and iron were significantly enriched with DEGs. The expression levels of the crucial genes from the functional analysis were also confirmed by quantitative PCR (qPCR). Conclusion: BBR can significantly improve hepatic steatosis in HCD-fed zebrafish larvae. Its mechanisms might be associated with the regulation of lipid metabolism, oxidative stress, and iron homeostasis. Raman imaging in larval zebrafish might become a useful tool for drug evaluation. Mainly, the gene expression profiles provide molecular information for BBR on the prevention and treatment of pediatric NAFLD.
Keywordberberine non-alcohol fatty liver disease Raman mapping larval zebrafish transcriptomics
DOI10.3389/fphar.2019.01504
Language英语
WOS KeywordHEPATIC STEATOSIS ; OXIDATIVE STRESS ; DISEASE ; CHILDREN ; STEATOHEPATITIS ; ACTIVATION ; INFLAMMATION ; ADOLESCENTS ; ASSOCIATION ; MICROBIOTA
Funding ProjectCAMS Initiative for Innovative Medicine[2016-I2M-1-011] ; Foundation for Innovative Research Groups of the National Natural Science Foundation of China[81621064] ; National Natural Science Foundation of China[81603172]
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
Funding OrganizationCAMS Initiative for Innovative Medicine ; Foundation for Innovative Research Groups of the National Natural Science Foundation of China ; National Natural Science Foundation of China
WOS IDWOS:000508837700001
PublisherFRONTIERS MEDIA SA
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Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/38865
Collection中国科学院过程工程研究所
Corresponding AuthorZhang, Jing-Pu; Hu, Chang-Qin
Affiliation1.Chinese Acad Med Sci & Peking Union Med Coll, Inst Med Biotechnol, Key Lab Biotechnol Antibiot, Natl Hlth Commiss, Beijing, Peoples R China
2.Chinese Acad Med Sci & Peking Union Med Coll, Inst Med Biotechnol, Beijing Key Lab Antimicrobial Agents, Beijing, Peoples R China
3.Capital Med Univ, Inst Cerebrovasc Dis Res, Xuanwu Hosp, Beijing, Peoples R China
4.China Resources Sanjiu Med & Pharmaceut Co Ltd, Postdoctoral Sci Res Workstn, Shenzhen, Peoples R China
5.Chinese Acad Sci, Inst Proc Engn, Postdoctoral Mobile Res Stn, Beijing, Peoples R China
6.Peking Union Med Coll, Natl Inst Food & Drug Control, Grad Sch, Beijing, Peoples R China
Recommended Citation
GB/T 7714
Chen, Bo,Zheng, Yang-Min,Zhang, Miao-Qing,et al. Microarray Expression Profiling and Raman Spectroscopy Reveal Anti-Fatty Liver Action of Berberine in a Diet-Induced Larval Zebrafish Model[J]. FRONTIERS IN PHARMACOLOGY,2020,10:15.
APA Chen, Bo,Zheng, Yang-Min,Zhang, Miao-Qing,Han, Ying,Zhang, Jing-Pu,&Hu, Chang-Qin.(2020).Microarray Expression Profiling and Raman Spectroscopy Reveal Anti-Fatty Liver Action of Berberine in a Diet-Induced Larval Zebrafish Model.FRONTIERS IN PHARMACOLOGY,10,15.
MLA Chen, Bo,et al."Microarray Expression Profiling and Raman Spectroscopy Reveal Anti-Fatty Liver Action of Berberine in a Diet-Induced Larval Zebrafish Model".FRONTIERS IN PHARMACOLOGY 10(2020):15.
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