학술논문
Potential Hepatoprotective Effects of Chamaecyparis lawsoniana against Methotrexate-Induced Liver Injury: Integrated Phytochemical Profiling, Target Network Analysis, and Experimental Validation.
Document Type
Academic Journal
Author
Fikry E; Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.; Orfali R; Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.; El-Sayed SS; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.; Perveen S; Department of Chemistry, School of Computer, Mathematical and Natural Sciences, Morgan State University, Baltimore, MD 21251, USA.; Ghafar S; Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.; El-Shafae AM; Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.; El-Domiaty MM; Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.; Tawfeek N; Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.
Source
Publisher: MDPI AG Country of Publication: Switzerland NLM ID: 101668981 Publication Model: Electronic Cited Medium: Print ISSN: 2076-3921 (Print) Linking ISSN: 20763921 NLM ISO Abbreviation: Antioxidants (Basel) Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
2076-3921
Abstract
Methotrexate (MTX) therapy encounters significant limitations due to the significant concern of drug-induced liver injury (DILI), which poses a significant challenge to its usage. To mitigate the deleterious effects of MTX on hepatic function, researchers have explored plant sources to discover potential hepatoprotective agents. This study investigated the hepatoprotective effects of the ethanolic extract derived from the aerial parts of Chamaecyparis lawsoniana (CLAE) against DILI, specifically focusing on MTX-induced hepatotoxicity. UPLC-ESI-MS/MS was used to identify 61 compounds in CLAE, with 31 potential bioactive compounds determined through pharmacokinetic analysis. Network pharmacology analysis revealed 195 potential DILI targets for the bioactive compounds, including TP53, IL6, TNF, HSP90AA1, EGFR, IL1B, BCL2, and CASP3 as top targets. In vivo experiments conducted on rats with acute MTX-hepatotoxicity revealed that administering CLAE orally at 200 and 400 mg/kg/day for ten days dose-dependently improved liver function, attenuated hepatic oxidative stress, inflammation, and apoptosis, and reversed the disarrayed hepatic histological features induced by MTX. In general, the findings of the present study provide evidence in favor of the hepatoprotective capabilities of CLAE in DILI, thereby justifying the need for additional preclinical and clinical investigations.