Ginsenoside Rg1

Pien-Tze-Huang (PTH) is a famous traditional Chinese patent medicine with excellent liver-protection effects. However, the mechanism of hepatoprotective action has not yet been entirely elucidated. This study aimed to elucidate the protective mechanism of PTH against alcoholic liver injury in rats from key targets. An alcoholic liver disease (ALD) model in male rats was established, and the rats were treated with PTH given at a prescribed dosage. The hepatoprotective components of PTH and their exposure in the serum of PTH-treated rats were systematically identified. Quantitative proteomics was employed to find differentially expressed proteins. The key targets were screened by bioinformatic analysis and further validated by Western blotting (WB) and molecular docking. Ursodeoxycholic acid, notoginsenoside R1, gypenoside XVII, ginsenoside Rb1, and ginsenoside Re may be important active hepatoprotective components of PTH. A total of 53 differentially expressed proteins that were reversed by PTH were successfully identified in rat liver tissues. Retinol metabolism and the PPAR signaling pathway may play a key role in ameliorating alcohol-induced liver injury after PTH intervention. In particular, protein CYP2, FATCD36, FATP, ACS, and CPT-2 in these two pathways may be key targets for the therapeutic effects of PTH, with the same reversal observed by WB. Molecular docking analysis further revealed that these five proteins exhibited generally stable binding with the five main components of PTH. The hepatoprotective effects of PTH may be exerted through the modulation of key targets within pivotal pathways. This work pioneered a comprehensive screening of the active compounds in PTH and elucidated the mechanisms and targets of their protective effects against alcoholic liver injury, providing a reference for the broader clinical application of PTH.