Abstract
Liver injury is a clinical disorder caused by toxins, drugs, and alcohol stimulation without effective therapeutic approaches thus far. Scutellarin (SCU), isolated from the edible herb Erigeron breviscapus (Vant.) Hand. -Mazz. showed potential hepatoprotective effects, but the mechanisms remain unknown. In this study, transcriptomics combined with nontargeted metabolomics and 16S rRNA amplicon sequencing were performed to elucidate the functional mechanisms of SCU in carbon tetrachloride (CCl4)–induced liver injury in mice. The results showed that SCU exerted potential hepatoprotective effects against CCl4-induced liver injury by repressing CYP2E1 and IκBα/NF-κB signaling pathways, modulating the gut microbiota (especially enriching Lactobacillus), and regulating the endogenous metabolites involved in lipid metabolism and bile acid homeostasis. SCU originates from a functional food that appears to be a promising agent to guard against liver injury.
Highlights
Liver injury is caused by a constellation of risk factors such as drug abuse and excessive alcohol consumption and can initiate cascades of pathophysiological processes, which subsequently contribute to the development of hepatosteatosis, hepatitis, and hepatic fibrosis, among others (Kremer et al, 2006; Chen et al, 2018; Qu et al, 2020)
We utilized transcriptomic analysis using RNA sequencing (RNA-seq) to identify the signaling pathways in the liver that are modified by SCU, and the results showed that expression of the nf-κb and cyp2e1 genes were significantly dampened
Bacteroidetes-to-Firmicutes ratio. (E) Z score analysis. (F) Selected three genera. (G) Spearman correlation analysis between gut microbiota and liver injury indicators, (*, **) indicates a significant correlation (p < 0.05, p < 0.01). (H) Prediction of microbiome function based on the KEGG database. (n 5). #p < 0.05, ##p < 0.01 vs. control group; *p < 0.05, **p < 0.01 vs. CCl4 group
Summary
Liver injury is caused by a constellation of risk factors such as drug abuse and excessive alcohol consumption and can initiate cascades of pathophysiological processes, which subsequently contribute to the development of hepatosteatosis, hepatitis, and hepatic fibrosis, among others (Kremer et al, 2006; Chen et al, 2018; Qu et al, 2020). Treatment strategies for liver injury remain extremely limited. Dietary flavonoids, including anthocyan, hyperoside, silymarin, and luteolin, are known for their beneficial effects on health and active roles in the prevention and treatment of a variety of diseases, such as cardiovascular disease, liver injury, fibrosis, and cancer (Gonçalves et al, 2009; Imran et al, 2019; Rahman et al, 2021; Zhang et al, 2021). The whole herb of E. breviscapus has been applied in the treatment of cerebral embolism, arachnoiditis, hemiplegia, and coronary artery disease for centuries in folk medicine (Liu et al, 2017; Zhu et al, 2018). The mechanisms by which SCU ameliorates liver injury have remained unknown until relatively recently
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