Affiliation:
1. Department of Genetic Engineering and Biotechnology University of Chittagong Chittagong Bangladesh
2. Department of Biochemistry and Molecular Biology University of Chittagong Chittagong Bangladesh
3. Department of Pharmacy International Islami University Chittagong Chittagong Bangladesh
4. Institute of Food Science and Technology, Bangladesh Council of Scientific and Industrial Research Dhaka Bangladesh
5. Department of Biochemistry, College of Science University of Jeddah Jeddah Saudi Arabia
Abstract
AbstractBackgroundMany kinds of orchids have significant health benefits although adequate research on their biological functions is yet to be carried out. This study investigated the paracetamol‐induced liver damage–protecting effect of epiphytic Aerides odorata methanol extract (AODE).MethodsThe protective effects of AODE were studied by analyzing its effect on liver function parameters, messenger RNA (mRNA) expression, and tissue histopathological architecture. The results were confirmed by ligand–receptor interaction of molecular docking and multitarget interaction of network pharmacological analyses.ResultsAODE significantly (p < 0.05) minimized the dose‐dependent increase in acid phosphatase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, 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 pharmacological properties. Additionally, in silico analysis showed that isoacteoside, one of the identified compounds, exhibited the best docking score (−11.42) with the liver protein 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.ConclusionThe findings demonstrate that AODE could be a novel hepatoprotective target in drug‐induced liver damage with a further single compound–based animal study.