DOI: 10.1002/ame2.12452
Ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry-characterized extract of Aerides odorata Lour alleviates paracetamol-induced hepatotoxicity in animal model evidenced by biochemical,molecular,and computational studies
A.M.Abu Ahmed1
Md.Atiar Rahman2
Farjana Sharmen1
A.S.M.Ali Reza3
Md.Shahidul Islam2
Md.Mamunur Rashid2
Md.Khalid Juhani Rafi2
Tanvir Ahmed Siddiqui2
Md.Muzahid Ahmed Ezaj4
Srabonti Saha2
Md.Nazim Uddin5
Walla Alelwani6
1.Department of Genetic Engineering and Biotechnology,University of Chittagong,Chittagong,Bangladesh;Department of Biochemistry and Molecular Biology,University of Chittagong,Chittagong,Bangladesh2.Department of Biochemistry and Molecular Biology,University of Chittagong,Chittagong,Bangladesh3.Department of Biochemistry and Molecular Biology,University of Chittagong,Chittagong,Bangladesh;Department of Pharmacy,International Islami University Chittagong,Chittagong,Bangladesh4.Department of Genetic Engineering and Biotechnology,University of Chittagong,Chittagong,Bangladesh5.Institute of Food Science and Technology,Bangladesh Council of Scientific and Industrial Research,Dhaka,Bangladesh6.Department of Biochemistry,College of Science,University of Jeddah,Jeddah,Saudi Arabia
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.
机标关键词：molecularstudiesliquidmodelhighmasstimeaerides
论文发表日期：2024-08-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：26( 497-522 )
英文信息