Potential Hepatoprotective Effects of <i>Chamaecyparis lawsoniana</i> against Methotrexate-Induced Liver Injury: Integrated Phytochemical Profiling, Target Network Analysis, and Experimental Validation
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 pote...
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| Format: | Article |
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MDPI AG
2023-12-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/12/2118 |
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| author | Eman Fikry Raha Orfali Shaimaa S. El-Sayed Shagufta Perveen Safina Ghafar Azza M. El-Shafae Maher M. El-Domiaty Nora Tawfeek |
| author_facet | Eman Fikry Raha Orfali Shaimaa S. El-Sayed Shagufta Perveen Safina Ghafar Azza M. El-Shafae Maher M. El-Domiaty Nora Tawfeek |
| author_sort | Eman Fikry |
| collection | DOAJ |
| description | 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 <i>Chamaecyparis lawsoniana</i> (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. |
| first_indexed | 2024-03-08T21:02:26Z |
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| id | doaj.art-4e9ff441f23248b08972f48c5b338e1e |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-08T21:02:26Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-4e9ff441f23248b08972f48c5b338e1e2023-12-22T13:48:37ZengMDPI AGAntioxidants2076-39212023-12-011212211810.3390/antiox12122118Potential Hepatoprotective Effects of <i>Chamaecyparis lawsoniana</i> against Methotrexate-Induced Liver Injury: Integrated Phytochemical Profiling, Target Network Analysis, and Experimental ValidationEman Fikry0Raha Orfali1Shaimaa S. El-Sayed2Shagufta Perveen3Safina Ghafar4Azza M. El-Shafae5Maher M. El-Domiaty6Nora Tawfeek7Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptDepartment of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptDepartment of Chemistry, School of Computer, Mathematical and Natural Sciences, Morgan State University, Baltimore, MD 21251, USADepartment of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaDepartment of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptDepartment of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptDepartment of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptMethotrexate (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 <i>Chamaecyparis lawsoniana</i> (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.https://www.mdpi.com/2076-3921/12/12/2118<i>Chamaecyparis lawsoniana</i>UPLC-ESI-MS/MSacute liver injurynetwork pharmacologydocking |
| spellingShingle | Eman Fikry Raha Orfali Shaimaa S. El-Sayed Shagufta Perveen Safina Ghafar Azza M. El-Shafae Maher M. El-Domiaty Nora Tawfeek Potential Hepatoprotective Effects of <i>Chamaecyparis lawsoniana</i> against Methotrexate-Induced Liver Injury: Integrated Phytochemical Profiling, Target Network Analysis, and Experimental Validation Antioxidants <i>Chamaecyparis lawsoniana</i> UPLC-ESI-MS/MS acute liver injury network pharmacology docking |
| title | Potential Hepatoprotective Effects of <i>Chamaecyparis lawsoniana</i> against Methotrexate-Induced Liver Injury: Integrated Phytochemical Profiling, Target Network Analysis, and Experimental Validation |
| title_full | Potential Hepatoprotective Effects of <i>Chamaecyparis lawsoniana</i> against Methotrexate-Induced Liver Injury: Integrated Phytochemical Profiling, Target Network Analysis, and Experimental Validation |
| title_fullStr | Potential Hepatoprotective Effects of <i>Chamaecyparis lawsoniana</i> against Methotrexate-Induced Liver Injury: Integrated Phytochemical Profiling, Target Network Analysis, and Experimental Validation |
| title_full_unstemmed | Potential Hepatoprotective Effects of <i>Chamaecyparis lawsoniana</i> against Methotrexate-Induced Liver Injury: Integrated Phytochemical Profiling, Target Network Analysis, and Experimental Validation |
| title_short | Potential Hepatoprotective Effects of <i>Chamaecyparis lawsoniana</i> against Methotrexate-Induced Liver Injury: Integrated Phytochemical Profiling, Target Network Analysis, and Experimental Validation |
| title_sort | potential hepatoprotective effects of i chamaecyparis lawsoniana i against methotrexate induced liver injury integrated phytochemical profiling target network analysis and experimental validation |
| topic | <i>Chamaecyparis lawsoniana</i> UPLC-ESI-MS/MS acute liver injury network pharmacology docking |
| url | https://www.mdpi.com/2076-3921/12/12/2118 |
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