Mechanism of arbutin in metabolic dysfunction-associated fatty liver disease based on multi-omics research

TL;DR

This study shows that arbutin can help treat fatty liver disease by reducing liver damage and restoring gut microbiota balance.

Contribution

The study reveals arbutin's anti-apoptotic and gut microbiota-regulating mechanisms in MAFLD treatment.

Findings

Arbutin improved liver injury in MAFLD mice by inhibiting apoptosis via STAT3 signaling.

Arbutin restored gut microbiota balance and altered fecal metabolite profiles in MAFLD mice.

Arbutin's therapeutic effects were confirmed using in vivo and in vitro models of MAFLD.

Abstract

Gut microbiota regulation is a key strategy for treating metabolic dysfunction-associated fatty liver disease (MAFLD). Arbutin (ARB) is a natural hydroquinone active agent with anti-inflammatory and antioxidant effects, as well as regulatory effects on the gut microbiota. However, its therapeutic effect on MAFLD and the responsible mechanisms remain unclear.

This study explored the therapeutic effect and mechanisms of ARB in MAFLD treatment.

High-fat diet (HFD)-fed mice served as the in vivo MAFLD model, and ARB treatment was given simultaneously. The extent of liver injury was assessed through histopathological staining. AML12 cells treated with free fatty acids served as the in vitro model. The effects of ARB were evaluated via oil red O staining and biochemical assays. Subsequently, we utilized bioinformatics techniques to predict the potential mechanisms and targets of ARB. The expression of liver apoptosis-related genes was detected using molecular biology techniques. Alterations in the gut microbiota were analyzed by 16S rRNA sequencing. Ultrahigh-performance liquid chromatography–high-resolution mass spectrometry was used to analyze the changes in fecal metabolite levels.

ARB treatment effectively improved liver injury in mice with MAFLD. Its mechanism was associated with anti-apoptotic effects mediated by signal transducer and activator of transcription 3. Meanwhile, ARB effectively reversed gut microbiota imbalance in mice with MAFLD and altered the composition of gut microbes and fecal metabolites.

ARB displayed potential effects in alleviating the pathology of MAFLD, exerting anti-apoptotic actions, and restoring the gut microbiota balance.

The online version contains supplementary material available at 10.1186/s40643-026-01032-5.

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