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Outline
To explore the mechanism of Mongolian medicine Zixin Dropping Pills (ZXDW) in treating non-alcoholic fatty liver disease (NAFLD), we combined network pharmacology with animal experiments. Network pharmacology identified 59 core targets of ZXDW for NAFLD, and functional enrichment analysis revealed that lipid metabolism pathway and phosphatidylinositol 3-kinase/protein kinase B (PI3K-AKT) signaling pathway were the key involved pathways. Pharmacodynamic experiments on high-fat diet-induced NAFLD in ApoE-/- mice confirmed that ZXDW alleviated hepatic lipid deposition, fibrosis and inflammation. Immunofluorescence and Western blot verified key targets in the functional pathways, showing that ZXDW significantly upregulated hepatic peroxisome proliferator-activated receptor gamma (PPARγ), liver X receptor alpha (LXRα), ATP-binding cassette subfamily A member 1 (ABCA1) and ATP-binding cassette subfamily G member 1 (ABCG1) protein expression, while downregulating PI3K, AKT and nuclear factor-kappa B (NF-κB) expression in ApoE-/- mice. Molecular docking between main components of ZXDW and the above targets indicated that costunolide, taurocholic acid and taurodeoxycholic acid might be the main active components. This study preliminarily confirms that ZXDW alleviates NAFLD through lipid metabolism and PI3K-AKT pathways, providing a theoretical basis for its clinical application. The experiment was approved by the Animal Ethics Committee of Inner Mongolia Medical University (approval No. YKD202401262).
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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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