Epiphytic Acampe ochracea orchid relieves paracetamol-induced hepatotoxicity by inhibiting oxidative stress and upregulating antioxidant genes in in vivo and virtual screening.

Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 8213295 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1950-6007 (Electronic) Linking ISSN: 07533322 NLM ISO Abbreviation: Biomed Pharmacother Subsets: MEDLINE

Publication: Paris : Editions Scientifiques Elsevier
Original Publication: New York, N.Y. : Masson Pub. USA, Inc., c1982-

Orchidaceae*/chemistry; Antioxidants/*pharmacology ; Chemical and Drug Induced Liver Injury/*prevention & control ; Liver/*drug effects ; Oxidative Stress/*drug effects ; Phytochemicals/*pharmacology ; Plant Extracts/*pharmacology; Acetaminophen ; Animals ; Antioxidants/isolation & purification ; Antioxidants/pharmacokinetics ; Aromatase/genetics ; Aromatase/metabolism ; Chemical and Drug Induced Liver Injury/genetics ; Chemical and Drug Induced Liver Injury/metabolism ; Chemical and Drug Induced Liver Injury/pathology ; Disease Models, Animal ; Estrogen Receptor alpha/genetics ; Estrogen Receptor alpha/metabolism ; Gene Expression Regulation ; Liver/metabolism ; Liver/pathology ; Male ; Mitogen-Activated Protein Kinase 14/genetics ; Mitogen-Activated Protein Kinase 14/metabolism ; Molecular Docking Simulation ; Network Pharmacology ; Oxidative Stress/genetics ; PPAR gamma/genetics ; PPAR gamma/metabolism ; Phytochemicals/isolation & purification ; Phytochemicals/pharmacokinetics ; Plant Extracts/isolation & purification ; Plant Extracts/pharmacokinetics ; Protein Interaction Maps ; Rats, Wistar ; Signal Transduction ; Vascular Endothelial Growth Factor A/genetics ; Vascular Endothelial Growth Factor A/metabolism ; Rats

Orchids are basically ornamental, and biological functions are seldom evaluated. This research investigated the effects of Acampe ochracea methanol extract (AOME) in ameliorating the paracetamol (PCM) induced liver injury in Wistar albino rats, evaluating its phytochemical status through UPLC-qTOF-MS analysis. With molecular docking and network pharmacology, virtual screening verified the inevitable interactions between the UPLC-qTOF-MS-characterized compounds and hepatoprotective drug receptors. The AOME has explicit a dose-dependent decrease of liver enzymes acid phosphatase (ACP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), total bilirubin, as well as an increase of serum total protein and antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GSH) with a virtual normalization (p < 0.05-p < 0.001) and the values were almost equivalent to the reference drug silymarin. After pretreatment with AOME, PCM-induced malondialdehyde (MDA) levels were considerably decreased (p < 0.001). Histopathological examinations corroborated the functional and biochemical findings. The AOME upregulated the genes involved in antioxidative (CAT, SOD, β-actin, PON1, and PFK1) and hepatoprotective mechanisms in PCM intoxicated rats. An array of 103 compounds has been identified from AOME through UPLC-qTOF-MS analysis. The detected compounds were substantially related to the targets of several liver proteins and antioxidative enzymes, according to an in silico study. Virtual prediction by SwissADME and admetSAR showed that AOME has drug-like, non-toxic, and potential pharmacological activities in hepatic damage. Furthermore, VEGFA, CYP19A1, MAPK14, ESR1, and PPARG genes interact with target compounds impacting the significant biological actions to recover PCM-induced liver damage.
(Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Keywords: Acampe ochracea; Antioxidant; Biochemical; Hepatoprotective; Liver and PCM; UPLC-qTOF-MS

0 (Antioxidants)
0 (Estrogen Receptor alpha)
0 (PPAR gamma)
0 (PPAR gamma, rat)
0 (Phytochemicals)
0 (Plant Extracts)
0 (Vascular Endothelial Growth Factor A)
0 (vascular endothelial growth factor A, rat)
362O9ITL9D (Acetaminophen)
EC 1.14.14.1 (Aromatase)
EC 1.14.14.1 (CYP19A1 protein, rat)
EC 2.7.11.24 (Mitogen-Activated Protein Kinase 14)

Date Created: 20211015 Date Completed: 20220127 Latest Revision: 20240226

20240226

10.1016/j.biopha.2021.112215

34649346