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March 13, 2026Open Access

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

Key Points

The aim is to assess the impact of diacerein on liver fibrosis, steatosis, and atherosclerosis in ApoE knockout mice fed a high-fat diet.
ApoE knockout mice were divided into three groups based on diacerein dosage.
Mice were fed a high-fat diet while receiving diacerein treatment.
Liver fat accumulation and fibrosis severity were measured alongside gene expression related to lipid metabolism.
Atherosclerotic burden was evaluated in the aorta using en face analysis.
Signaling pathways were verified in vitro.
Diacerein treatment led to a dose-dependent reduction in collagen fibers and fat accumulation in the liver.
Expression of fibrosis-related genes decreased with diacerein treatment.
A trend toward reduced atherosclerotic plaque burden was observed in the aorta with diacerein.
Diacerein treatment decreased levels of pro-inflammatory cytokines like TNF-α.

Abstract

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. Key messages 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. Graphical Abstract

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