Glycyrrhizic acid attenuates the malignant biological properties of nonalcoholic fatty liver disease-related...

Area of Science:

• Hepatology
• Oncology
• Pharmacology

Background:

• Nonalcoholic fatty liver disease (NAFLD) is a growing concern, often progressing to hepatocellular carcinoma (HCC).
• Glycyrrhizic acid (GA), derived from licorice, exhibits anti-hepatic fibrosis and anti-tumor properties.
• The efficacy of GA in mitigating NAFLD-associated HCC requires further investigation.

Purpose of the Study:

• To investigate the inhibitory effects of Glycyrrhizic acid (GA) on nonalcoholic fatty liver disease-related hepatocellular carcinoma (NAFLD-HCC).
• To elucidate the underlying molecular mechanisms, particularly the KKβ/NF-κB pathway.

Main Methods:

• Cellular assays (CCK-8, proliferation, migration, invasion, apoptosis) were performed on L-02 and HepG2 cells, with L-02 cells induced by palmitic acid (PA).
• A rat model of HCC was established using high-fat diets and diethylnitrosamine.
• The KKβ/NF-κB pathway was analyzed in both cellular and animal models.

Main Results:

• GA alleviated lipid deposition and inflammation in PA-induced L-02 cells.
• GA inhibited proliferation, migration, and invasion while promoting apoptosis in HepG2 cells.
• In HCC model rats, GA reduced liver index, body weight, liver weight, nodules, infiltration, and increased apoptosis.
• GA significantly attenuated the KKβ/NF-κB pathway activation in both cell and rat models.

Conclusions:

• Glycyrrhizic acid (GA) demonstrates significant inhibitory effects on the progression of NAFLD-related HCC.
• The KKβ/NF-κB pathway is a key target for GA's therapeutic action in NAFLD-HCC.
• GA holds potential as a therapeutic agent for treating NAFLD-associated HCC.