Study on the hepatoprotective effects of Thymus quinquecostatus Celak. against alcoholic liver injury based on system pharmacology strategy

Alcoholic liver disease (ALD) is a global prevailing disorder. Thymus quinquecostatus Celak. (TQC) is a food additive and edible herb which possesses hepatoprotective activity against ALD. But the mechanisms involved remain largely unknown. In this study, system pharmacology strategy based on in vivo composition analysis, network pharmacology, molecular docking, and experimental validation was conducted to investigate the mechanisms and material basis of Thymus quinquecostatus Celak. extracts (TQE) against ALD. Through UPLC-QE-Orbitrap-MS/MS analysis, 41 prototypes from TQE were identified in mouse plasma. Then 19 hub ingredients and 146 related hub genes were obtained based on network pharmacology analysis. Protein-protein interaction (PPI) network, molecular docking and experimental verification study further confirmed the effect of TQE on tumor protein p53 (TP53), epidermal growth factor receptor (EGFR), AKT serine/threonine kinase 1 (AKT1), mitogen-activated protein kinase 1 (MAPK1), and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1). In conclusion, the hepatoprotective activity of TQC against ALD can be attributed to 19 main active ingredients. They might play an essential role in the management of ALD through EGFR, MAPK, and TP53 pathways.