TY - JOUR
T1 - Network-Pharmacology-Based Study on Active Phytochemicals and Molecular Mechanism of Cnidium monnieri in Treating Hepatocellular Carcinoma
AU - Khan, Shakeel Ahmad
AU - Lee, Terence Kin Wah
N1 - Funding Information:
Funding: This research was funded by the National Natural Science Foundation of China, grant number 81871935 and “The APC was funded by 81871935”.
Funding Information:
Acknowledgments: The authors would like to express their profound gratitude to PolyU Distinguished Postdoctoral Fellowship Scheme at The Hong Kong Polytechnic University, Hong Kong, and the grant mentioned above to support this research work.
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/5/12
Y1 - 2022/5/12
N2 - 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.
AB - 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.
KW - active phytochemicals
KW - Cnidium monnieri
KW - hepatocellular carcinoma
KW - molecular mechanism
KW - network pharmacology
UR - http://www.scopus.com/inward/record.url?scp=85129901184&partnerID=8YFLogxK
U2 - 10.3390/ijms23105400
DO - 10.3390/ijms23105400
M3 - Journal article
C2 - 35628212
AN - SCOPUS:85129901184
SN - 1661-6596
VL - 23
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 10
M1 - 5400
ER -