Pure total flavonoids from citrus improve nonalcoholic steatohepatitis liver inflammatory responses by regulating the...

Area of Science:

• Hepatology and Pharmacology
• Molecular Biology
• Biochemistry

Background:

• Nonalcoholic steatohepatitis (NASH) is an advanced stage of nonalcoholic fatty liver disease (NAFLD) with significant prognostic implications.
• Pure total flavonoids from circus (PTFC) show promise in alleviating NASH symptoms, but the precise molecular mechanisms require elucidation.
• Previous omics screening identified the CCL2/CCR2-PI3K-Akt signaling pathway as crucial for regulating hepatic inflammatory responses.

Purpose of the Study:

• To investigate the therapeutic effects of PTFC on a mouse model of NASH.
• To elucidate the underlying mechanism by which PTFC ameliorates NASH, focusing on the CCL2/CCR2-PI3K-Akt signaling pathway.

Main Methods:

• NASH was induced in mice using a high-fat diet (HFD), followed by PTFC treatment.
• Liver histopathology was assessed using Hematoxylin-eosin and oil red O staining.
• Western blotting, real-time PCR, liquid suspension array, and biochemical assays were employed to analyze molecular changes and biochemical parameters.

Main Results:

• PTFC treatment significantly improved liver histopathology, reduced serum transaminase and lipid levels, and decreased liver and serum proinflammatory cytokines in HFD mice.
• PTFC administration markedly reduced the mRNA and protein expression, as well as phosphorylation levels, of key molecules within the CCL2/CCR2-PI3K-Akt signaling pathway.
• These findings indicate a substantial amelioration of NASH-related pathologies and inflammatory markers following PTFC intervention.

Conclusions:

• PTFC demonstrates significant efficacy in ameliorating NASH symptoms.
• The therapeutic mechanism of PTFC in NASH is associated with the modulation of the CCL2/CCR2-PI3K-Akt signaling pathway.
• PTFC effectively reduces liver inflammation, offering a potential therapeutic strategy for NASH management.