Computer-Aided Screening of Phytoconstituents from <i>Ocimum tenuiflorum</i> against Diabetes Mellitus Targeting DPP4 Inhibition: A Combination of Molecular Docking, Molecular Dynamics, and Pharmacokinetics Approaches
Diabetes mellitus is a major global health concern in the current scenario which is chiefly characterized by the rise in blood sugar levels or hyperglycemia. In the context, DPP4 enzyme plays a critical role in glucose homeostasis. DPP4 targets and inactivates incretin hormones such as glucagon-like...
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MDPI AG
2022-08-01
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| Series: | Molecules |
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| author | Harshit Sajal Shashank M. Patil Ranjith Raj Abdullah M. Shbeer Mohammed Ageel Ramith Ramu |
| author_facet | Harshit Sajal Shashank M. Patil Ranjith Raj Abdullah M. Shbeer Mohammed Ageel Ramith Ramu |
| author_sort | Harshit Sajal |
| collection | DOAJ |
| description | Diabetes mellitus is a major global health concern in the current scenario which is chiefly characterized by the rise in blood sugar levels or hyperglycemia. In the context, DPP4 enzyme plays a critical role in glucose homeostasis. DPP4 targets and inactivates incretin hormones such as glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) as physiological substrates, which are essential to regulate the amount of insulin that is secreted after eating. Since the inactivation of incretins occurs, the hyperglycemic conditions continue to rise, and result in adverse physiological conditions linked with diabetes mellitus. Hence, inhibition of DPP4 has been the center of focus in the present antidiabetic studies. Although few DPP4 inhibitor drugs, such as alogliptin, saxagliptin, linagliptin, and sitagliptin, are available, their adverse effects on human metabolism are undeniable. Therefore, it becomes essential for the phytochemical intervention of the disease using computational methods prior to performing in vitro and in vivo studies. In this regard, we used an in-silico approach involving molecular docking, molecular dynamics simulations, and binding free energy calculations to investigate the inhibitory potential of <i>Ocimum tenuiflorum</i> phytocompounds against DPP4. In this regard, three phytocompounds (1S-α-pinene, β-pinene, and dehydro-<i>p</i>-cymene) from <i>O. tenuiflorum</i> have been discovered as the potential inhibitors of the DPP4 protein. To summarize, from our in-silico experiment outcomes, we propose dehydro-<i>p</i>-cymene as the potential lead inhibitor of DPP4 protein, thereby discovering new a phytocompound for the effective management of hyperglycemia and diabetes mellitus. The reported compound can be taken for in vitro and in vivo analyses in near future. |
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| language | English |
| last_indexed | 2024-03-09T04:02:51Z |
| publishDate | 2022-08-01 |
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| series | Molecules |
| spelling | doaj.art-bdb2da9f18b742b0b3f430b681c8ccc12023-12-03T14:11:07ZengMDPI AGMolecules1420-30492022-08-012716513310.3390/molecules27165133Computer-Aided Screening of Phytoconstituents from <i>Ocimum tenuiflorum</i> against Diabetes Mellitus Targeting DPP4 Inhibition: A Combination of Molecular Docking, Molecular Dynamics, and Pharmacokinetics ApproachesHarshit Sajal0Shashank M. Patil1Ranjith Raj2Abdullah M. Shbeer3Mohammed Ageel4Ramith Ramu5Department of Biotechnology and Bioinformatics, JSS Academy of Higher Education and Research, Mysuru 570015, IndiaDepartment of Biotechnology and Bioinformatics, JSS Academy of Higher Education and Research, Mysuru 570015, IndiaDepartment of Pharmacology, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru 570015, IndiaDepartment of Surgery, Faculty of Medicine, Jazan University, Jazan 45142, Saudi ArabiaDepartment of Surgery, Faculty of Medicine, Jazan University, Jazan 45142, Saudi ArabiaDepartment of Biotechnology and Bioinformatics, JSS Academy of Higher Education and Research, Mysuru 570015, IndiaDiabetes mellitus is a major global health concern in the current scenario which is chiefly characterized by the rise in blood sugar levels or hyperglycemia. In the context, DPP4 enzyme plays a critical role in glucose homeostasis. DPP4 targets and inactivates incretin hormones such as glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) as physiological substrates, which are essential to regulate the amount of insulin that is secreted after eating. Since the inactivation of incretins occurs, the hyperglycemic conditions continue to rise, and result in adverse physiological conditions linked with diabetes mellitus. Hence, inhibition of DPP4 has been the center of focus in the present antidiabetic studies. Although few DPP4 inhibitor drugs, such as alogliptin, saxagliptin, linagliptin, and sitagliptin, are available, their adverse effects on human metabolism are undeniable. Therefore, it becomes essential for the phytochemical intervention of the disease using computational methods prior to performing in vitro and in vivo studies. In this regard, we used an in-silico approach involving molecular docking, molecular dynamics simulations, and binding free energy calculations to investigate the inhibitory potential of <i>Ocimum tenuiflorum</i> phytocompounds against DPP4. In this regard, three phytocompounds (1S-α-pinene, β-pinene, and dehydro-<i>p</i>-cymene) from <i>O. tenuiflorum</i> have been discovered as the potential inhibitors of the DPP4 protein. To summarize, from our in-silico experiment outcomes, we propose dehydro-<i>p</i>-cymene as the potential lead inhibitor of DPP4 protein, thereby discovering new a phytocompound for the effective management of hyperglycemia and diabetes mellitus. The reported compound can be taken for in vitro and in vivo analyses in near future.https://www.mdpi.com/1420-3049/27/16/5133DPP4 inhibition<i>Ocimum tenuiflorum</i>in silico approachmolecular dockingmolecular dynamics simulationsbinding free energy calculations |
| spellingShingle | Harshit Sajal Shashank M. Patil Ranjith Raj Abdullah M. Shbeer Mohammed Ageel Ramith Ramu Computer-Aided Screening of Phytoconstituents from <i>Ocimum tenuiflorum</i> against Diabetes Mellitus Targeting DPP4 Inhibition: A Combination of Molecular Docking, Molecular Dynamics, and Pharmacokinetics Approaches Molecules DPP4 inhibition <i>Ocimum tenuiflorum</i> in silico approach molecular docking molecular dynamics simulations binding free energy calculations |
| title | Computer-Aided Screening of Phytoconstituents from <i>Ocimum tenuiflorum</i> against Diabetes Mellitus Targeting DPP4 Inhibition: A Combination of Molecular Docking, Molecular Dynamics, and Pharmacokinetics Approaches |
| title_full | Computer-Aided Screening of Phytoconstituents from <i>Ocimum tenuiflorum</i> against Diabetes Mellitus Targeting DPP4 Inhibition: A Combination of Molecular Docking, Molecular Dynamics, and Pharmacokinetics Approaches |
| title_fullStr | Computer-Aided Screening of Phytoconstituents from <i>Ocimum tenuiflorum</i> against Diabetes Mellitus Targeting DPP4 Inhibition: A Combination of Molecular Docking, Molecular Dynamics, and Pharmacokinetics Approaches |
| title_full_unstemmed | Computer-Aided Screening of Phytoconstituents from <i>Ocimum tenuiflorum</i> against Diabetes Mellitus Targeting DPP4 Inhibition: A Combination of Molecular Docking, Molecular Dynamics, and Pharmacokinetics Approaches |
| title_short | Computer-Aided Screening of Phytoconstituents from <i>Ocimum tenuiflorum</i> against Diabetes Mellitus Targeting DPP4 Inhibition: A Combination of Molecular Docking, Molecular Dynamics, and Pharmacokinetics Approaches |
| title_sort | computer aided screening of phytoconstituents from i ocimum tenuiflorum i against diabetes mellitus targeting dpp4 inhibition a combination of molecular docking molecular dynamics and pharmacokinetics approaches |
| topic | DPP4 inhibition <i>Ocimum tenuiflorum</i> in silico approach molecular docking molecular dynamics simulations binding free energy calculations |
| url | https://www.mdpi.com/1420-3049/27/16/5133 |
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