A network pharmacology approach with experimental validation to discover protective mechanism of poly herbal extract on diabetes mellitus
Objective: Polyherbal extracts (PHE) contain six traditional medicinal plants, and the efficacy of the medicinal plants used in the preparation of this PHE has been confirmed for the treatment of diseases like diabetes mellitus (DM). The aim of this study was to evaluate the efficacy and therapeutic...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Journal of King Saud University: Science |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1018364724000508 |
| _version_ | 1797262908276604928 |
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| author | Amit Kumar Singh Pradeep Kumar Sunil Kumar Mishra KavindraNath Tiwari Anand Kumar Singh Ajay Kumar Pandey Ali A. Shati Mohammad Y. Alfaifi SeragEldin I. Elbehairi R.Z. Sayyed |
| author_facet | Amit Kumar Singh Pradeep Kumar Sunil Kumar Mishra KavindraNath Tiwari Anand Kumar Singh Ajay Kumar Pandey Ali A. Shati Mohammad Y. Alfaifi SeragEldin I. Elbehairi R.Z. Sayyed |
| author_sort | Amit Kumar Singh |
| collection | DOAJ |
| description | Objective: Polyherbal extracts (PHE) contain six traditional medicinal plants, and the efficacy of the medicinal plants used in the preparation of this PHE has been confirmed for the treatment of diseases like diabetes mellitus (DM). The aim of this study was to evaluate the efficacy and therapeutic mechanism of PHE through a network pharmacology approach to reveal the protective mechanism of Alpha-Tocospiro A (ATA) present in PHE on DM with experimental validation. Methods: In this study, Lipinski's rule (Swiss ADME) and drug-likeness score (MolSoft's) web pages were used to confirm the drug-likeness of identified constituents in PHE. Swiss Target Prediction (STP) genes were found for ATA-related genes. The DisGeNet database was used to screen genes associated with DM. String created a network diagram of the interactions between the ATA and DM genes. Top-scoring genes from the string network through CytoNCA plugged into Cytoscape 3.8.2 were selected as hub genes. In addition, the ShinyGO database is used to predict GO and KEGG pathway enrichment analyses. Results: A total of 675 and 105 therapeutic genes (STP) were associated with all bioactive compounds and ATA in the PHE screen, respectively. Additionally, a maximum of 2,803 DM-related genes (DisGeNet) were observed. Further, in the analysis, 331, 57 potential (intersecting) genes were identified in the correlation between the target genes of all compounds and ATA, respectively, of PHE and the target genes of DM. The identified hub gene “TNF” for both ATA and PHE was found to be precisely strengthened in 49 pathways, along with 14 signaling pathways out of more than 100 enriched KEGG pathways. This study predicted that ATA activates PI3K/Akt and MAPK pathways enriched with TNF by phosphorylating the insulin receptor (IR) β-subunit. The anti-diabetic activity of PHE was found to be good and primarily confirmed by in vitro α-glucosidase enzyme inhibition activity. Conclusion: The anti-diabetic activity of PHE was found to be effective and was confirmed by the enzyme inhibition activity in the primary study. This study predicted that ATA is a novel drug molecule in PHE that has a targeted mechanism of action and therapeutic effect on DM. |
| first_indexed | 2024-03-07T22:00:53Z |
| format | Article |
| id | doaj.art-28c238cc459741a9b5ac0caaa5bf98d1 |
| institution | Directory Open Access Journal |
| issn | 1018-3647 |
| language | English |
| last_indexed | 2024-04-25T00:04:35Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of King Saud University: Science |
| spelling | doaj.art-28c238cc459741a9b5ac0caaa5bf98d12024-03-14T06:13:52ZengElsevierJournal of King Saud University: Science1018-36472024-04-01364103138A network pharmacology approach with experimental validation to discover protective mechanism of poly herbal extract on diabetes mellitusAmit Kumar Singh0Pradeep Kumar1Sunil Kumar Mishra2KavindraNath Tiwari3Anand Kumar Singh4Ajay Kumar Pandey5Ali A. Shati6Mohammad Y. Alfaifi7SeragEldin I. Elbehairi8R.Z. Sayyed9Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology, Banaras Hindu University, Varanasi, Pradesh 221005, IndiaDepartment of Botany, MMV, Banaras Hindu University, Varanasi 221005, IndiaDepartment of Pharmaceutical Engineering & Technology, Indian Institute of Technology, Banaras Hindu University, Varanasi, Pradesh 221005, India; Corresponding author.Department of Botany, MMV, Banaras Hindu University, Varanasi 221005, IndiaDepartment of Chemistry, PG College, Mariahu, VBS Purvanchal University, Jaunpur 222161, IndiaDepartment of Kaychikitsa, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, IndiaBiology Department, Faculty of Science, King Khalid University, Abha 9004, Saudi ArabiaBiology Department, Faculty of Science, King Khalid University, Abha 9004, Saudi ArabiaBiology Department, Faculty of Science, King Khalid University, Abha 9004, Saudi ArabiaDepartment of Microbiology, PSGVP Mandal's S I Patil Arts, G B Patel Science and STKV Sangh Commerce College, Shahada 425409, IndiaObjective: Polyherbal extracts (PHE) contain six traditional medicinal plants, and the efficacy of the medicinal plants used in the preparation of this PHE has been confirmed for the treatment of diseases like diabetes mellitus (DM). The aim of this study was to evaluate the efficacy and therapeutic mechanism of PHE through a network pharmacology approach to reveal the protective mechanism of Alpha-Tocospiro A (ATA) present in PHE on DM with experimental validation. Methods: In this study, Lipinski's rule (Swiss ADME) and drug-likeness score (MolSoft's) web pages were used to confirm the drug-likeness of identified constituents in PHE. Swiss Target Prediction (STP) genes were found for ATA-related genes. The DisGeNet database was used to screen genes associated with DM. String created a network diagram of the interactions between the ATA and DM genes. Top-scoring genes from the string network through CytoNCA plugged into Cytoscape 3.8.2 were selected as hub genes. In addition, the ShinyGO database is used to predict GO and KEGG pathway enrichment analyses. Results: A total of 675 and 105 therapeutic genes (STP) were associated with all bioactive compounds and ATA in the PHE screen, respectively. Additionally, a maximum of 2,803 DM-related genes (DisGeNet) were observed. Further, in the analysis, 331, 57 potential (intersecting) genes were identified in the correlation between the target genes of all compounds and ATA, respectively, of PHE and the target genes of DM. The identified hub gene “TNF” for both ATA and PHE was found to be precisely strengthened in 49 pathways, along with 14 signaling pathways out of more than 100 enriched KEGG pathways. This study predicted that ATA activates PI3K/Akt and MAPK pathways enriched with TNF by phosphorylating the insulin receptor (IR) β-subunit. The anti-diabetic activity of PHE was found to be good and primarily confirmed by in vitro α-glucosidase enzyme inhibition activity. Conclusion: The anti-diabetic activity of PHE was found to be effective and was confirmed by the enzyme inhibition activity in the primary study. This study predicted that ATA is a novel drug molecule in PHE that has a targeted mechanism of action and therapeutic effect on DM.http://www.sciencedirect.com/science/article/pii/S1018364724000508Poly herbal extract (PHE)Alpha Tocospiro A (ATA)Diabetes mellitus (DM)KEGGMolecular simulationMM/GBSA |
| spellingShingle | Amit Kumar Singh Pradeep Kumar Sunil Kumar Mishra KavindraNath Tiwari Anand Kumar Singh Ajay Kumar Pandey Ali A. Shati Mohammad Y. Alfaifi SeragEldin I. Elbehairi R.Z. Sayyed A network pharmacology approach with experimental validation to discover protective mechanism of poly herbal extract on diabetes mellitus Journal of King Saud University: Science Poly herbal extract (PHE) Alpha Tocospiro A (ATA) Diabetes mellitus (DM) KEGG Molecular simulation MM/GBSA |
| title | A network pharmacology approach with experimental validation to discover protective mechanism of poly herbal extract on diabetes mellitus |
| title_full | A network pharmacology approach with experimental validation to discover protective mechanism of poly herbal extract on diabetes mellitus |
| title_fullStr | A network pharmacology approach with experimental validation to discover protective mechanism of poly herbal extract on diabetes mellitus |
| title_full_unstemmed | A network pharmacology approach with experimental validation to discover protective mechanism of poly herbal extract on diabetes mellitus |
| title_short | A network pharmacology approach with experimental validation to discover protective mechanism of poly herbal extract on diabetes mellitus |
| title_sort | network pharmacology approach with experimental validation to discover protective mechanism of poly herbal extract on diabetes mellitus |
| topic | Poly herbal extract (PHE) Alpha Tocospiro A (ATA) Diabetes mellitus (DM) KEGG Molecular simulation MM/GBSA |
| url | http://www.sciencedirect.com/science/article/pii/S1018364724000508 |
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