Abstract
BackgroundNonalcoholic fatty liver disease (NAFLD) is a common liver disorder that currently lacks effective treatment. Berberine (BBR), a botanic compound isolated from traditional Chinese medicine, exhibits a potent therapeutic potential for the metabolic disease. The current study aimed to understand the mechanisms underlying the therapeutic effect of BBR in NAFLD.MethodsWe performed systematical analyses on hepatic expression profiles of mRNAs and long noncoding RNAs (lncRNAs) in a high-fat diet (HFD)-induced steatotic animal model with or without BBR treatment. The study was conducted by using the methods of bioinformatics, including hierarchical clustering, gene enrichment and gene co-expression networks analysis. The effect of BBR on the expression profile of some interesting genes was confirmed by quantitative RT-PCR and further studied in a human hepatic cell line, Huh7.ResultsWe found that a large group of genes including 881 mRNAs and 538 lncRNAs whose expression in the steatotic liver was reversed by BBR treatment, suggesting a global effect of BBR in modulating hepatic gene expression profiles. Among the BBR-regulated genes, we identified several modules and numerous significant genes that were associated with liver metabolism and NAFLD-related functions. Specifically, a conserved lncRNA, MRAK052686, was found strongly correlated with the antioxidant factor Nrf2, and both genes were down-regulated by the steatotic liver. Moreover, the reduced expression of MRAK052686 and Nrf2 was completely reversed by BBR treatment, suggesting a new mechanism accounting for the therapeutic effect of BBR.ConclusionsThe findings for the first time provide a new genetic insight into the pharmaceutical mechanism of BBR in protecting against NAFLD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0383-6) contains supplementary material, which is available to authorized users.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is a common liver disorder that currently lacks effective treatment
BBR ameliorates hepatic steatosis in high-fat diet (HFD)-fed rats BBR has been reported to prevent the development of NAFLD in animal models [12,36,37]
To confirm the therapeutic effect of BBR, we examined the effect of BBR on the liver in HFD-induced obese rats
Summary
Nonalcoholic fatty liver disease (NAFLD) is a common liver disorder that currently lacks effective treatment. NAFLD can progress from hepatic steatosis to steatohepatitis, leading to an increased susceptibility of Berberine (BBR), isolated from the herb Rhizoma Coptidis, has been widely used in traditional Chinese medicine to treat diarrhea and many other inflammatory diseases [6]. BBR can function as a cholesterol-lowering drug via a unique mechanism distinct from statins [9] These findings suggest a potential therapeutic activity of BBR for NAFLD. Both in vitro and in vivo studies from our previous work and many others have shown that BBR profoundly inhibited lipid synthesis and accumulation in hepatocytes, attenuated hepatic steatosis and hyperlipidemia, and prevented the progression of NAFLD [10,11,12,13,14]. It appears that multiple mechanisms are involved in the therapeutic effect of BBR, leading us to hypothesize that BBR may have a global effect in modulating gene expression profile in the liver and thereby protecting against hepatic steastosis
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