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Network-Pharmacology-Based Study on Active Phytochemicals and Molecular Mechanism of Cnidium monnieri in Treating Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a malignancy with a high mortality rate globally. For thousands of years, Cnidium monnieri has been used to treat human ailments and is regarded as a veritable treasure trove for drug discovery. This study has investigated the key active phytochemicals and molecular...

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Autores principales: Khan, Shakeel Ahmad, Lee, Terence Kin Wah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9140548/
https://www.ncbi.nlm.nih.gov/pubmed/35628212
http://dx.doi.org/10.3390/ijms23105400
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author Khan, Shakeel Ahmad
Lee, Terence Kin Wah
author_facet Khan, Shakeel Ahmad
Lee, Terence Kin Wah
author_sort Khan, Shakeel Ahmad
collection PubMed
description Hepatocellular carcinoma (HCC) is a malignancy with a high mortality rate globally. For thousands of years, Cnidium monnieri has been used to treat human ailments and is regarded as a veritable treasure trove for drug discovery. This study has investigated the key active phytochemicals and molecular mechanisms of Cnidium monnieri implicated in curing HCC. We utilized the TCMSP database to collect data on the phytochemicals of Cnidium monnieri. The SwissTargetPrediction website tool was used to predict the targets of phytochemicals of Cnidium monnieri. HCC-related genes were retrieved from OncoDB.HCC and Liverome, two liver-cancer-related databases. Using the DAVID bioinformatic website tool, Gene Ontology (GO) and KEGG enrichment analysis were performed on the intersecting targets of HCC-related genes and active phytochemicals in Cnidium monnieri. A network of active phytochemicals and anti-HCC targets was constructed and analyzed using Cytoscape software. Molecular docking of key active phytochemicals was performed with anti-HCC targets using AutoDock Vina (version 1.2.0.). We identified 19 active phytochemicals in Cnidium monnieri, 532 potential targets of these phytochemicals, and 566 HCC-related genes. Results of GO enrichment indicated that Cnidium monnieri might be implicated in affecting gene targets involved in multiple biological processes, such as protein phosphorylation, negative regulation of the apoptotic process, which could be attributed to its anti-HCC effects. KEGG pathway analyses indicated that the PI3K–AKT signaling pathway, pathways in cancer, proteoglycans in cancer, the TNF signaling pathway, VEGF signaling pathway, ErbB signaling pathway, and EGFR tyrosine kinase inhibitor resistance are the main pathways implicated in the anti-HCC effects of Cnidium monnieri. Molecular docking analyses showed that key active phytochemicals of Cnidium monnieri, such as ar-curcumene, diosmetin, and (E)-2,3-bis(2-keto-7-methoxy-chromen-8-yl)acrolein, can bind to core therapeutic targets EGFR, CASP3, ESR1, MAPK3, CCND1, and ERBB2. The results of the present study offer clues for further investigation of the anti-HCC phytochemicals and mechanisms of Cnidium monnieri and provide a basis for developing modern anti-HCC drugs based on phytochemicals in Cnidium monnieri.
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spelling pubmed-91405482022-05-28 Network-Pharmacology-Based Study on Active Phytochemicals and Molecular Mechanism of Cnidium monnieri in Treating Hepatocellular Carcinoma Khan, Shakeel Ahmad Lee, Terence Kin Wah Int J Mol Sci Article Hepatocellular carcinoma (HCC) is a malignancy with a high mortality rate globally. For thousands of years, Cnidium monnieri has been used to treat human ailments and is regarded as a veritable treasure trove for drug discovery. This study has investigated the key active phytochemicals and molecular mechanisms of Cnidium monnieri implicated in curing HCC. We utilized the TCMSP database to collect data on the phytochemicals of Cnidium monnieri. The SwissTargetPrediction website tool was used to predict the targets of phytochemicals of Cnidium monnieri. HCC-related genes were retrieved from OncoDB.HCC and Liverome, two liver-cancer-related databases. Using the DAVID bioinformatic website tool, Gene Ontology (GO) and KEGG enrichment analysis were performed on the intersecting targets of HCC-related genes and active phytochemicals in Cnidium monnieri. A network of active phytochemicals and anti-HCC targets was constructed and analyzed using Cytoscape software. Molecular docking of key active phytochemicals was performed with anti-HCC targets using AutoDock Vina (version 1.2.0.). We identified 19 active phytochemicals in Cnidium monnieri, 532 potential targets of these phytochemicals, and 566 HCC-related genes. Results of GO enrichment indicated that Cnidium monnieri might be implicated in affecting gene targets involved in multiple biological processes, such as protein phosphorylation, negative regulation of the apoptotic process, which could be attributed to its anti-HCC effects. KEGG pathway analyses indicated that the PI3K–AKT signaling pathway, pathways in cancer, proteoglycans in cancer, the TNF signaling pathway, VEGF signaling pathway, ErbB signaling pathway, and EGFR tyrosine kinase inhibitor resistance are the main pathways implicated in the anti-HCC effects of Cnidium monnieri. Molecular docking analyses showed that key active phytochemicals of Cnidium monnieri, such as ar-curcumene, diosmetin, and (E)-2,3-bis(2-keto-7-methoxy-chromen-8-yl)acrolein, can bind to core therapeutic targets EGFR, CASP3, ESR1, MAPK3, CCND1, and ERBB2. The results of the present study offer clues for further investigation of the anti-HCC phytochemicals and mechanisms of Cnidium monnieri and provide a basis for developing modern anti-HCC drugs based on phytochemicals in Cnidium monnieri. MDPI 2022-05-12 /pmc/articles/PMC9140548/ /pubmed/35628212 http://dx.doi.org/10.3390/ijms23105400 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Khan, Shakeel Ahmad
Lee, Terence Kin Wah
Network-Pharmacology-Based Study on Active Phytochemicals and Molecular Mechanism of Cnidium monnieri in Treating Hepatocellular Carcinoma
title Network-Pharmacology-Based Study on Active Phytochemicals and Molecular Mechanism of Cnidium monnieri in Treating Hepatocellular Carcinoma
title_full Network-Pharmacology-Based Study on Active Phytochemicals and Molecular Mechanism of Cnidium monnieri in Treating Hepatocellular Carcinoma
title_fullStr Network-Pharmacology-Based Study on Active Phytochemicals and Molecular Mechanism of Cnidium monnieri in Treating Hepatocellular Carcinoma
title_full_unstemmed Network-Pharmacology-Based Study on Active Phytochemicals and Molecular Mechanism of Cnidium monnieri in Treating Hepatocellular Carcinoma
title_short Network-Pharmacology-Based Study on Active Phytochemicals and Molecular Mechanism of Cnidium monnieri in Treating Hepatocellular Carcinoma
title_sort network-pharmacology-based study on active phytochemicals and molecular mechanism of cnidium monnieri in treating hepatocellular carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9140548/
https://www.ncbi.nlm.nih.gov/pubmed/35628212
http://dx.doi.org/10.3390/ijms23105400
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