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Updated: Jun 12, 2026
In Vitro Modeling of Fat Deposition in Metabolic Dysfunction-Associated Steatotic Liver Disease
Published on: July 19, 2024
Parthenolide ameliorates metabolic dysfunction-associated steatohepatitis by inhibiting M1 polarization by
Abstract:
Metabolic dysfunction-associated steatohepatitis (MASH) is an inflammatory disorder that results in ongoing liver inflammation and injury. During the course of hepatitis, parthenolide (PAR) promotes the recovery of liver function. Using a mouse model of MASH, the present study aimed to assess the effect of PAR on the condition. The MASH mouse model was developed using a high-fat diet combined with high-carbohydrate drinking, and measurements were taken for body weight, liver-to-body mass ratio, non-alcoholic fatty liver disease activity score, and levels of alanine aminotransferase and aspartate aminotransferase. Subsequently, liver injury was detected using hematoxyling and eosin staining, hepatic lipid accumulation was evaluated with oil red O staining, and liver fibrosis was assessed through Masson staining. Macrophage infiltration and M1 polarization were assessed by immunofluorescence staining for F4/80; and lipid metabolic, fibrotic, and pro-inflammatory indicators were detected by RT-qPCR; nuclear factor-κB (NF-κB) signaling pathway was assessed by Western blot. We found that PAR alleviated liver injury, improved lipid metabolism, and reduced fibrosis in MASH mice,. It also lowered macrophage infiltration in the liver, particularly decreasing M1 macrophages and pro-inflammatory cytokines. PAR inhibited the activation of the NF-κB pathway, and the protective effects were attenuated by an NF-κB pathway activators. We conclude that PAR ameliorates liver injury, hepatic lipid metabolism, fibrosis and inflammation in MASH mice, likely by suppressing the NF-κB pathway and thereby inhibiting M1 polarization.
Insights
Parthenolide (PAR) effectively treats metabolic dysfunction-associated steatohepatitis (MASH) in mice by reducing liver inflammation, injury, and fibrosis. PAR works by inhibiting the NF-κB pathway, which decreases M1 macrophage polarization and improves lipid metabolism.
Area of Science:
- Hepatology
- Immunology
- Pharmacology
Background:
- Metabolic dysfunction-associated steatohepatitis (MASH) is a severe liver condition characterized by inflammation and injury.
- Parthenolide (PAR) has shown potential in promoting liver function recovery during hepatitis.
Purpose of the Study:
- To investigate the therapeutic effects of parthenolide (PAR) on a mouse model of MASH.
- To elucidate the underlying mechanisms of PAR's action, focusing on inflammation, lipid metabolism, and fibrosis.
Main Methods:
- A MASH mouse model was established using a high-fat diet and high-carbohydrate drinking.
- Evaluated liver injury, lipid accumulation, fibrosis, macrophage infiltration (M1 polarization), and NF-κB pathway activation.
- Utilized techniques including H&E staining, Oil Red O staining, Masson staining, immunofluorescence, RT-qPCR, and Western blot.
Main Results:
- PAR significantly alleviated liver injury, reduced hepatic lipid accumulation, and ameliorated liver fibrosis in MASH mice.
- PAR decreased macrophage infiltration, specifically M1 polarization, and lowered pro-inflammatory cytokine levels.
- PAR inhibited the activation of the NF-κB signaling pathway, with protective effects diminished by pathway activators.
Conclusions:
- Parthenolide demonstrates significant therapeutic potential for MASH, improving liver injury, lipid metabolism, fibrosis, and inflammation.
- PAR's protective effects are likely mediated through the suppression of the NF-κB pathway, leading to reduced M1 macrophage polarization.
