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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

2022; Elsevier BV; Volume: 309; Linguagem: Inglês

10.1016/j.lfs.2022.121044

1879-0631

Chandan Kumar Sarkar, Milon Mondal, Khattab Al-Khafaji, Dina M. El‐Kersh, Sarmin Jamaddar, Pranta Ray, Uttam Kumar Roy, Mirola Afroze, Md. Moniruzzaman, Mala Khan, Umma Hafsa Asha, Abul Bashar Ripon Khalipha, Edna Mori, Bruna Caroline Gonçalves Vasconcelos de Lacerda, Isaac Moura Araújo, Henrique Douglas Melo Coutinho, Manik Chandra Shill, Muhammad Torequl Islam,

Cholinesterase and Neurodegenerative Diseases

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.