Network pharmacology combined with molecular docking and in vitro verification reveals the therapeutic potential of Delphinium roylei munz constituents on breast carcinoma
Delphinium roylei Munz is an indigenous medicinal plant to India where its activity against cancer has not been previously investigated, and its specific interactions of bioactive compounds with vulnerable breast cancer drug targets remain largely unknown. Therefore, in the current study, we aimed t...
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1135898/full |
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| author | Wajahat Rashid Mir Basharat Ahmad Bhat Ashish Kumar Rohan Dhiman Mustfa Alkhanani Abdullah Almilaibary Mohd Younis Dar Showkat Ahmad Ganie Manzoor Ahmad Mir |
| author_facet | Wajahat Rashid Mir Basharat Ahmad Bhat Ashish Kumar Rohan Dhiman Mustfa Alkhanani Abdullah Almilaibary Mohd Younis Dar Showkat Ahmad Ganie Manzoor Ahmad Mir |
| author_sort | Wajahat Rashid Mir |
| collection | DOAJ |
| description | Delphinium roylei Munz is an indigenous medicinal plant to India where its activity against cancer has not been previously investigated, and its specific interactions of bioactive compounds with vulnerable breast cancer drug targets remain largely unknown. Therefore, in the current study, we aimed to evaluate the anti-breast cancer activity of different extracts of D. roylei against breast cancer and deciphering the molecular mechanism by Network Pharmacology combined with Molecular Docking and in vitro verification. The experimental plant was extracted with various organic solvents according to their polarity index. Phytocompounds were identified by High resolution-liquid chromatography-mass spectrometry (HR-LC/MS) technique, and SwissADME programme evaluated their physicochemical properties. Next, target(s) associated with the obtained bioactives or breast cancer-related targets were retrieved by public databases, and the Venn diagram selected the overlapping targets. The networks between overlapping targets and bioactive were visualized, constructed, and analyzed by STRING programme and Cytoscape software. Finally, we implemented a molecular docking test (MDT) using AutoDock Vina to explore key target(s) and compound(s). HR-LC/MS detected hundreds of phytocompounds, and few were accepted by Lipinski’s rules after virtual screening and therefore classified as drug-like compounds (DLCs). A total of 464 potential target genes were attained for the nine quantitative phytocompounds and using Gene Cards, OMIM and DisGeNET platforms, 12063 disease targets linked to breast cancer were retrieved. With Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment, a total of 20 signalling pathways were manifested, and a hub signalling pathway (PI3K-Akt signalling pathway), a key target (Akt1), and a key compound (8-Hydroxycoumarin) were selected among the 20 signalling pathways via molecular docking studies. The molecular docking investigation revealed that among the nine phytoconstituents, 8-hydroxycoumarin showed the best binding energy (−9.2 kcal/mol) with the Akt1 breast cancer target. 8-hydroxycoumarin followed all the ADME property prediction using SwissADME, and 100 nanoseconds (ns) MD simulations of 8-hydroxycoumarin complexes with Akt1 were found to be stable. Furthermore, D. roylei extracts also showed significant antioxidant and anticancer activity through in vitro studies. Our findings indicated for the first time that D. roylei extracts could be used in the treatment of BC. |
| first_indexed | 2024-03-12T11:26:42Z |
| format | Article |
| id | doaj.art-dc61a7e541884cfa99b27d910ed62341 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-12T11:26:42Z |
| publishDate | 2023-09-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-dc61a7e541884cfa99b27d910ed623412023-09-01T08:09:01ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-09-011410.3389/fphar.2023.11358981135898Network pharmacology combined with molecular docking and in vitro verification reveals the therapeutic potential of Delphinium roylei munz constituents on breast carcinomaWajahat Rashid Mir0Basharat Ahmad Bhat1Ashish Kumar2Rohan Dhiman3Mustfa Alkhanani4Abdullah Almilaibary5Mohd Younis Dar6Showkat Ahmad Ganie7Manzoor Ahmad Mir8Department of Bio-Resources, School of Biological Sciences, University of Kashmir, Srinagar, Jammu and Kashmir, IndiaDepartment of Bio-Resources, School of Biological Sciences, University of Kashmir, Srinagar, Jammu and Kashmir, IndiaDepartment of Life Science, National Institute of Technology, Rourkela, Odisha, IndiaDepartment of Life Science, National Institute of Technology, Rourkela, Odisha, IndiaDepartment of Family and Community Medicine, Faculty of Medicine, Al Baha University, Al Bahah, Saudi ArabiaDepartment of Biology, College of Science, Hafr Al Batin University of Hafr Al-Batin, Hafar Al Batin, Saudi ArabiaRegional Research Institute of Unani Medicine (RRIUM), University of Kashmir, Srinagar, Jammu and Kashmir, IndiaDepartment of Clinical Biochemistry, School of Biological Sciences, University of Kashmir, Srinagar, Jammu and Kashmir, IndiaDepartment of Bio-Resources, School of Biological Sciences, University of Kashmir, Srinagar, Jammu and Kashmir, IndiaDelphinium roylei Munz is an indigenous medicinal plant to India where its activity against cancer has not been previously investigated, and its specific interactions of bioactive compounds with vulnerable breast cancer drug targets remain largely unknown. Therefore, in the current study, we aimed to evaluate the anti-breast cancer activity of different extracts of D. roylei against breast cancer and deciphering the molecular mechanism by Network Pharmacology combined with Molecular Docking and in vitro verification. The experimental plant was extracted with various organic solvents according to their polarity index. Phytocompounds were identified by High resolution-liquid chromatography-mass spectrometry (HR-LC/MS) technique, and SwissADME programme evaluated their physicochemical properties. Next, target(s) associated with the obtained bioactives or breast cancer-related targets were retrieved by public databases, and the Venn diagram selected the overlapping targets. The networks between overlapping targets and bioactive were visualized, constructed, and analyzed by STRING programme and Cytoscape software. Finally, we implemented a molecular docking test (MDT) using AutoDock Vina to explore key target(s) and compound(s). HR-LC/MS detected hundreds of phytocompounds, and few were accepted by Lipinski’s rules after virtual screening and therefore classified as drug-like compounds (DLCs). A total of 464 potential target genes were attained for the nine quantitative phytocompounds and using Gene Cards, OMIM and DisGeNET platforms, 12063 disease targets linked to breast cancer were retrieved. With Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment, a total of 20 signalling pathways were manifested, and a hub signalling pathway (PI3K-Akt signalling pathway), a key target (Akt1), and a key compound (8-Hydroxycoumarin) were selected among the 20 signalling pathways via molecular docking studies. The molecular docking investigation revealed that among the nine phytoconstituents, 8-hydroxycoumarin showed the best binding energy (−9.2 kcal/mol) with the Akt1 breast cancer target. 8-hydroxycoumarin followed all the ADME property prediction using SwissADME, and 100 nanoseconds (ns) MD simulations of 8-hydroxycoumarin complexes with Akt1 were found to be stable. Furthermore, D. roylei extracts also showed significant antioxidant and anticancer activity through in vitro studies. Our findings indicated for the first time that D. roylei extracts could be used in the treatment of BC.https://www.frontiersin.org/articles/10.3389/fphar.2023.1135898/fullDelphinium royleibreast cancerHR/LC-MS8-hydroxycoumarinanticancer activitynetwork pharmacology |
| spellingShingle | Wajahat Rashid Mir Basharat Ahmad Bhat Ashish Kumar Rohan Dhiman Mustfa Alkhanani Abdullah Almilaibary Mohd Younis Dar Showkat Ahmad Ganie Manzoor Ahmad Mir Network pharmacology combined with molecular docking and in vitro verification reveals the therapeutic potential of Delphinium roylei munz constituents on breast carcinoma Frontiers in Pharmacology Delphinium roylei breast cancer HR/LC-MS 8-hydroxycoumarin anticancer activity network pharmacology |
| title | Network pharmacology combined with molecular docking and in vitro verification reveals the therapeutic potential of Delphinium roylei munz constituents on breast carcinoma |
| title_full | Network pharmacology combined with molecular docking and in vitro verification reveals the therapeutic potential of Delphinium roylei munz constituents on breast carcinoma |
| title_fullStr | Network pharmacology combined with molecular docking and in vitro verification reveals the therapeutic potential of Delphinium roylei munz constituents on breast carcinoma |
| title_full_unstemmed | Network pharmacology combined with molecular docking and in vitro verification reveals the therapeutic potential of Delphinium roylei munz constituents on breast carcinoma |
| title_short | Network pharmacology combined with molecular docking and in vitro verification reveals the therapeutic potential of Delphinium roylei munz constituents on breast carcinoma |
| title_sort | network pharmacology combined with molecular docking and in vitro verification reveals the therapeutic potential of delphinium roylei munz constituents on breast carcinoma |
| topic | Delphinium roylei breast cancer HR/LC-MS 8-hydroxycoumarin anticancer activity network pharmacology |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1135898/full |
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