Microarray Expression Profiling and Raman Spectroscopy Reveal Anti-Fatty Liver Action of Berberine in a Diet-Induced Larval Zebrafish Model
TL;DR: A larval zebrafish model is employed to mimic the therapeutic effects of BBR in the pediatric population and the mechanisms underlying its hepatoprotection to provide molecular information for BBR on the prevention and treatment of pediatric NAFLD.
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Abstract: Background: 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 μM. 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 μM) 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.
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Citations
The pharmacological activity of berberine, a review for liver protection
Mengting Zhou,Ying Deng,Meichen Liu,Li Liao,Xuyang Dai,Chaocheng Guo,Xingtao Zhao,Linfeng He,Cheng Peng,Yunxia Li +9 more
TL;DR: The pharmacological activities of lipid metabolism regulation, bile acid adjustment,Anti-inflammation, oxidation resistance, anti-fibrosis and anti-cancer and so on are summarized, providing a reference for the safe and effective clinical use of berberine.
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Berberine attenuates hepatic oxidative stress in rats with non-alcoholic fatty liver disease via the Nrf2/ARE signalling pathway.
Yuanjun Deng,Kairui Tang,Runsen Chen,Huan Nie,Shu Liang,Jin-wen Zhang,Yupei Zhang,Qinhe Yang +7 more
TL;DR: BBR may alleviate hepatic oxidative stress in rats with NAFLD, which may be partly attributed to the activation of the Nrf2/ARE signalling pathway.
Research progress in use of traditional Chinese medicine monomer for treatment of non-alcoholic fatty liver disease.
TL;DR: Wang et al. as mentioned in this paper summarized the experimental and clinical evidence of TCM monomers for the treatment of NAFLD in the past six years (2015-2020), thus providing thoughts and prospects for further exploring the pathogenesis of non-alcoholic fatty liver disease.
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Dietary berberine regulates lipid metabolism in muscle and liver of black sea bream (Acanthopagrus schlegelii) fed normal or high-lipid diets.
TL;DR: Dietary BBR supplementation in the HL diet reduced hepatic lipid accumulation by down-regulating lipogenesis gene expression and up- Regulating lipolysis gene expression, and it increased muscle lipid contents with opposite trends of the mechanism observed in the liver.
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Syntaxin 1B Mediates Berberine's Roles in Epilepsy-Like Behavior in a Pentylenetetrazole-Induced Seizure Zebrafish Model.
TL;DR: It is demonstrated that STX1B protein levels are negatively correlated with a seizure and can decrease the sensitivity of the photosensitive response in a PTZ-induced seizure zebrafish larvae; furthermore, STx1B may partially mediate the anticonvulsant effect of BBR.
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