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Tytuł:
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GC-MS analysis, and evaluation of protective effect of Piper chaba stem bark against paracetamol-induced liver damage in Sprague-Dawley rats: Possible defensive mechanism by targeting CYP2E1 enzyme through in silico study.
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Autorzy:
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Sarkar C; Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh.
Mondal M; Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh.
Al-Khafaji K; College of Dentistry, The University of Mashreq, Baghdad, Iraq.
El-Kersh DM; Pharmacognosy Department, Faculty of Pharmacy, The British University in Egypt (BUE), El Shorouk, Cairo Governorate, Egypt.
Jamaddar S; Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh.
Ray P; Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh.
Roy UK; Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh.
Afroze M; Bangladesh Reference Institute for Chemical Measurements (BRiCM), Dr. Qudrat- e- Khuda Road (Laboratory Road), Dhanmondi, Dhaka 1205, Bangladesh.
Moniruzzaman M; Bangladesh Reference Institute for Chemical Measurements (BRiCM), Dr. Qudrat- e- Khuda Road (Laboratory Road), Dhanmondi, Dhaka 1205, Bangladesh.
Khan M; Bangladesh Reference Institute for Chemical Measurements (BRiCM), Dr. Qudrat- e- Khuda Road (Laboratory Road), Dhanmondi, Dhaka 1205, Bangladesh.
Asha UH; Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh.
Khalipha ABR; Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh.
Mori E; CECAPE - College of Dentistry, Av. Padre Cícero, 3917 - São José, Juazeiro do Norte, CE 63024-015, Brazil.
de Lacerda BCGV; CECAPE - College of Dentistry, Av. Padre Cícero, 3917 - São José, Juazeiro do Norte, CE 63024-015, Brazil.
Araújo IM; Department of Biological Chemistry, Regional University of Cariri (URCA), Crato, Ceará 63105-000, Brazil.
Coutinho HDM; Department of Biological Chemistry, Regional University of Cariri (URCA), Crato, Ceará 63105-000, Brazil. Electronic address: .
Shill MC; Department of Pharmaceutical Sciences, North South University, Bashundhara, Dhaka 1229, Bangladesh.
Islam MT; Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh. Electronic address: .
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Źródło:
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Life sciences [Life Sci] 2022 Nov 15; Vol. 309, pp. 121044. Date of Electronic Publication: 2022 Oct 05.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: <2008->: Amsterdam : Elsevier
Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press.
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MeSH Terms:
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Piper*
Chemical and Drug Induced Liver Injury*/pathology
Alkaloids*/pharmacology
Silymarin*/pharmacology
Rats ; Animals ; Acetaminophen/toxicity ; Rats, Sprague-Dawley ; Cytochrome P-450 CYP2E1 ; Gas Chromatography-Mass Spectrometry ; Methanol/pharmacology ; Plant Bark ; Plant Extracts/therapeutic use ; Liver ; Bilirubin ; Lipids/pharmacology ; Fatty Acids ; Serum Albumin ; Esters/pharmacology
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Contributed Indexing:
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Keywords: CYP2E1; GC–MS; Piper chaba
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Substance Nomenclature:
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362O9ITL9D (Acetaminophen)
U71XL721QK (piperine)
EC 1.14.13.- (Cytochrome P-450 CYP2E1)
Y4S76JWI15 (Methanol)
0 (Plant Extracts)
0 (Alkaloids)
0 (Silymarin)
RFM9X3LJ49 (Bilirubin)
0 (Lipids)
0 (Fatty Acids)
0 (Serum Albumin)
0 (Esters)
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Entry Date(s):
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Date Created: 20221008 Date Completed: 20221020 Latest Revision: 20221020
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Update Code:
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20240105
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DOI:
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10.1016/j.lfs.2022.121044
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PMID:
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36208657
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The present study attempted to scrutinize the protective effect of the methanolic extract of P. chaba stem bark against paracetamol-induced hepatotoxicity in Sprague-Dawley rats, along with the gas chromatography-mass spectrometry (GC-MS) analysis to identify phytochemicals, which were further docked in the catalytic site of CYP2E1 and the MD simulation for system that plays a major role in the bio-activation of toxic substances that produce reactive metabolites, leading to hepatotoxicity. P. chaba stem methanol extract (250 and 500 mg/kg) were treated orally with the negative control and the negative control silymarin (50 mg/kg) groups. Phytochemical profiling was conducted using GC-MS. In in-silico studies, PyRx software was used for docking analysis and the stability of the binding mode in the target active sites was evaluated through a set of standard MD-simulation protocols using the Charmm 27 force field and Swiss PARAM. Co-administration of P. chaba at both doses with APAP significantly reduced the APAP-augmented liver marker enzymes ALT, AST, ALP, and LDH, along with serum albumin, globulin, hepatic enzymes, histopathological architecture, lipid profiles, total protein, and total bilirubin, and elevated the levels of MDA. The GC-MS analysis indicated that P. chaba extract is enriched in fatty acid methyl esters (46.23 %) and alkaloids (10.91 %) and piperine is represented as a main phytochemical. Among all the identified phytochemicals, piperine (-8.0 kcal/mol) was found to be more interacting and stable with the binding site of CYP2E1. Therefore, all of our findings may conclude that the P. chaba stem extract and its main compound, piperine, are able to neutralize APAP-induced hepatic damage.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
