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This study aims to investigate the pharmacological effects of procyanidin B3 (Pro B3) on non-alcoholic fatty liver disease (NAFLD) and its molecular mechanism underlying the regulation of fatty acid oxidation (FAO) in hepatocytes during NAFLD, thereby providing experimental evidence for the clinical application of Pro B3 in NAFLD. Mice were fed a high-fat diet (HFD) for 12 weeks to induce NAFLD and received oral gavage administration for 12 weeks. The pharmacological effect of Pro B3 in improving NAFLD was assessed through serum biochemical indexes, liver pathological changes and lipid droplet formation in the liver using Hematoxylin-eosin (H & E) staining and oil red O staining. This study protocol was approved by the Experimental Animal Ethics Committee of Gannan Medical University (approval No.: 2025443). In the in vitro experiments, the HepG2 cells were induced with a mixture of palmitic acid and oleic acid (2∶1) to create a cellular model of NAFLD and evaluate the cytotoxicity and cell viability of ProB3 on HepG2 cells. The expressions of FAO-associated genes such as acyl-CoA synthetase long chain family member 5 (ACSL5), carnitine palmitoyltransferase 1 (CPT1), acetyl-CoA carboxylase (ACC), and GATA binding protein 3 (GATA3) were detected by immunohistochemical, immunofluorescence, qRT-PCR and Western blot. Mechanistically, the JASPAR database and dual-luciferase reporter gene assays were used to explore the transcription factors and binding sites of ACSL5. By silencing GATA3 using siRNA, the effects of Pro B3 on the expression of ACSL5 and lipid deposition were examined. The results demonstrated that Pro B3 significantly improves the NAFLD-related indicators in mice, reduces serum lipid levels and lipid droplet accumulation in HepG2 cells, and up-regulates the expression of FAO-related genes, such as ACSL5, CPT1, ACC. Furthermore, GATA3 might be a transcription factor of ACSL5, and the transcriptional regulatory site might be "ACATAG". Moreover, Pro B3 significantly upregulated the expression of GATA3 mRNA and protein levels, while silencing GATA3 significantly inhibited the expression of ACSL5 mRNA and protein levels, as well as weakened the inhibitory effect of Pro B3 on lipid accumulation in HepG2 cells. In conclusion, Pro B3 may be an effective lead compound for treating NAFLD by promoting FAO in hepatocytes through regulation of the GATA3/ACSL5 pathway, thereby ameliorating NAFLD.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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