Network-Pharmacology-Based Study on Active Phytochemicals and Molecular Mechanism of <i>Cnidium monnieri</i> in Treating Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is a malignancy with a high mortality rate globally. For thousands of years, <i>Cnidium monnieri</i> 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 phytochem...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-05-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/10/5400 |
| _version_ | 1797499272874164224 |
|---|---|
| author | Shakeel Ahmad Khan Terence Kin Wah Lee |
| author_facet | Shakeel Ahmad Khan Terence Kin Wah Lee |
| author_sort | Shakeel Ahmad Khan |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC) is a malignancy with a high mortality rate globally. For thousands of years, <i>Cnidium monnieri</i> 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 <i>Cnidium monnieri</i> implicated in curing HCC. We utilized the TCMSP database to collect data on the phytochemicals of <i>Cnidium monnieri</i>. The SwissTargetPrediction website tool was used to predict the targets of phytochemicals of <i>Cnidium monnieri</i>. 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 <i>Cnidium monnieri</i>. 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 <i>Cnidium monnieri</i>, 532 potential targets of these phytochemicals, and 566 HCC-related genes. Results of GO enrichment indicated that <i>Cnidium monnieri</i> 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 <i>Cnidium monnieri</i>. Molecular docking analyses showed that key active phytochemicals of <i>Cnidium monnieri</i>, 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 <i>Cnidium monnieri</i> and provide a basis for developing modern anti-HCC drugs based on phytochemicals in <i>Cnidium monnieri</i>. |
| first_indexed | 2024-03-10T03:45:06Z |
| format | Article |
| id | doaj.art-178ca2786c5b40cd8a09abfe97145750 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:45:06Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-178ca2786c5b40cd8a09abfe971457502023-11-23T11:22:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-05-012310540010.3390/ijms23105400Network-Pharmacology-Based Study on Active Phytochemicals and Molecular Mechanism of <i>Cnidium monnieri</i> in Treating Hepatocellular CarcinomaShakeel Ahmad Khan0Terence Kin Wah Lee1Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, 11 Yuk Choi Rd., Hung Hom, Kowloon 999077, Hong KongDepartment of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, 11 Yuk Choi Rd., Hung Hom, Kowloon 999077, Hong KongHepatocellular carcinoma (HCC) is a malignancy with a high mortality rate globally. For thousands of years, <i>Cnidium monnieri</i> 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 <i>Cnidium monnieri</i> implicated in curing HCC. We utilized the TCMSP database to collect data on the phytochemicals of <i>Cnidium monnieri</i>. The SwissTargetPrediction website tool was used to predict the targets of phytochemicals of <i>Cnidium monnieri</i>. 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 <i>Cnidium monnieri</i>. 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 <i>Cnidium monnieri</i>, 532 potential targets of these phytochemicals, and 566 HCC-related genes. Results of GO enrichment indicated that <i>Cnidium monnieri</i> 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 <i>Cnidium monnieri</i>. Molecular docking analyses showed that key active phytochemicals of <i>Cnidium monnieri</i>, 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 <i>Cnidium monnieri</i> and provide a basis for developing modern anti-HCC drugs based on phytochemicals in <i>Cnidium monnieri</i>.https://www.mdpi.com/1422-0067/23/10/5400<i>Cnidium monnieri</i>network pharmacologyactive phytochemicalsmolecular mechanismhepatocellular carcinoma |
| spellingShingle | Shakeel Ahmad Khan Terence Kin Wah Lee Network-Pharmacology-Based Study on Active Phytochemicals and Molecular Mechanism of <i>Cnidium monnieri</i> in Treating Hepatocellular Carcinoma International Journal of Molecular Sciences <i>Cnidium monnieri</i> network pharmacology active phytochemicals molecular mechanism hepatocellular carcinoma |
| title | Network-Pharmacology-Based Study on Active Phytochemicals and Molecular Mechanism of <i>Cnidium monnieri</i> in Treating Hepatocellular Carcinoma |
| title_full | Network-Pharmacology-Based Study on Active Phytochemicals and Molecular Mechanism of <i>Cnidium monnieri</i> in Treating Hepatocellular Carcinoma |
| title_fullStr | Network-Pharmacology-Based Study on Active Phytochemicals and Molecular Mechanism of <i>Cnidium monnieri</i> in Treating Hepatocellular Carcinoma |
| title_full_unstemmed | Network-Pharmacology-Based Study on Active Phytochemicals and Molecular Mechanism of <i>Cnidium monnieri</i> in Treating Hepatocellular Carcinoma |
| title_short | Network-Pharmacology-Based Study on Active Phytochemicals and Molecular Mechanism of <i>Cnidium monnieri</i> in Treating Hepatocellular Carcinoma |
| title_sort | network pharmacology based study on active phytochemicals and molecular mechanism of i cnidium monnieri i in treating hepatocellular carcinoma |
| topic | <i>Cnidium monnieri</i> network pharmacology active phytochemicals molecular mechanism hepatocellular carcinoma |
| url | https://www.mdpi.com/1422-0067/23/10/5400 |
| work_keys_str_mv | AT shakeelahmadkhan networkpharmacologybasedstudyonactivephytochemicalsandmolecularmechanismoficnidiummonnieriiintreatinghepatocellularcarcinoma AT terencekinwahlee networkpharmacologybasedstudyonactivephytochemicalsandmolecularmechanismoficnidiummonnieriiintreatinghepatocellularcarcinoma |