# Diacerein improves liver fibrosis, steatosis, and atherosclerosis in ApoE knockout mice

## TL;DR

Diacerein reduces liver damage and atherosclerosis in mice with a genetic predisposition to these conditions.

## Contribution

This study demonstrates diacerein's dual anti-inflammatory and anti-fibrotic effects in a mouse model of metabolic disorders.

## Key findings

- Diacerein reduced liver fat accumulation and collagen fibers in a dose-dependent manner.
- Atherosclerotic plaque burden decreased with diacerein treatment, along with reduced pro-inflammatory cytokine expression.
- The drug improved liver fibrosis and steatosis in high-fat diet-fed apoE knockout mice.

## Abstract

Non-alcoholic fatty liver disease and atherosclerosis may share a common pathogenesis involving chronic IL-1β-induced inflammation. We aimed to evaluate the efficacy of diacerein, an IL-1 pathway inhibitor, in improving liver fibrosis, steatosis, and atherosclerosis in apolipoprotein E-knockout (apoE k/o) mice. ApoE k/o mice fed a high-fat diet (HFD) were divided into three groups based on diacerein dosage. Liver fat accumulation and fibrosis severity were compared across groups, along with changes in the expression of genes related to lipid metabolism and fibrosis. Atherosclerotic burden in the aorta was evaluated via en face analysis, and the related signaling pathway was verified in vitro. Diacerein treatment reduced the amount of collagen fibers and fat accumulation in the liver in a dose-dependent manner as well as fibrosis-related gene expression. Atherosclerotic plaque burden in the aorta showed a decreasing trend with diacerein treatment, accompanied by reduced expression of pro-inflammatory cytokines, including TNF-α. Diacerein treatment ameliorated liver steatosis/fibrosis and showed beneficial effects on atherosclerosis-related mechanisms in HFD-fed apoE k/o mice. Given its dual anti-inflammatory and anti-fibrotic actions, diacerein represents a promising therapeutic candidate for metabolic disorders characterized by chronic inflammation.

We analyzed the effects of diacerein on liver fibrosis, steatosis, and atherosclerosis in apolipoprotein E knockout (apoE k/o) mice.Diacerein reduced fat accumulation in the liver and collagen fibers in the liver.It decreased the expression of genes related to fibrosis and the burden of atherosclerotic plaque in the aorta.The expression of pro-inflammatory cytokines was reduced.Treatment of apoE knockout mice fed an HFD with diacerein effectively ameliorated liver steatosis/fibrosis and atherosclerosis.

We analyzed the effects of diacerein on liver fibrosis, steatosis, and atherosclerosis in apolipoprotein E knockout (apoE k/o) mice.

Diacerein reduced fat accumulation in the liver and collagen fibers in the liver.

It decreased the expression of genes related to fibrosis and the burden of atherosclerotic plaque in the aorta.

The expression of pro-inflammatory cytokines was reduced.

Treatment of apoE knockout mice fed an HFD with diacerein effectively ameliorated liver steatosis/fibrosis and atherosclerosis.

The online version contains supplementary material available at 10.1007/s00109-026-02653-1.