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-protec...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.展开更多
文摘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.
