摘要Background:Many kinds of orchids have significant health benefits although ade-quate research on their biological functions is yet to be carried out.This study inves-tigated the paracetamol-induced liver damage-protecting effect of epiphytic Aerides odorata methanol extract (AODE).Methods:The protective effects of AODE were studied by analyzing its effect on liver function parameters,messenger RNA (mRNA) expression,and tissue histopatho-logical architecture.The results were confirmed by ligand-receptor interaction of molecular docking and multitarget interaction of network pharmacological analyses.Results:AODE significantly ( p<0.05) minimized the dose-dependent increase in acid phosphatase,aspartate aminotransferase,alanine aminotransferase,alkaline phos-phatase,γ-glutamyl transferase,lactate dehydrogenase,and total bilirubin compared to the reference drug silymarin.Malondialdehyde level decreased,and the antioxidant genes catalase ( CAT ),superoxide dismutase ( SOD ),β-actin,paraoxonase-1 ( PON1 ),and phosphofructokinase-1 ( PFK-1 ) were upregulated in AODE-treated paracetamol-intoxicated rats.A total of 376 compounds comprising phenols and flavonoids were identified using ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-qTOF-MS).The online toxicity assessment using SwissADME and admetSAR exhibited drug-like,nontoxic,and potential pharmaco-logical properties.Additionally,in silico analysis showed that isoacteoside,one of the identified compounds,exhibited the best docking score (-11.42) with the liver pro-tein human pituitary adenylate cyclase-1 (Protein Data Bank ID:3N94).Furthermore,network pharmacology analysis identified the top 10 hub genes,namely AKT1 (protein kinase B),CTNNB1 (catenin beta-1),SRC (proto-oncogene c-Src),TNF (tumor necrosis factor),EGFR (epidermal growth factor receptor),HSP90AA1 ( heat shock protein 90α ),MAPK3 (mitogen-activated protein kinase 3),STAT3 (signal transducer and activator of transcription 3),CASP3 (caspase protein),and ESR1 (estrogen receptor 1),which are responsible for hepatoprotective activity.Conclusion:The findings demonstrate that AODE could be a novel hepatoprotective target in drug-induced liver damage with a further single compound-based animal study.