Integrated Mechanisms of Polarity–Based Extracts of <i>Cucumis melo</i> L. Seed Kernels for Airway Smooth Muscle Relaxation via Key Signaling Pathways Based on WGCNA, In Vivo, and In Vitro Analyses
The present study aimed to determine the mechanisms responsible for calcium–mediated smooth muscle contractions in <i>C. melo</i> seeds. The phytochemicals of <i>C. melo</i> were identified and quantified with the aid of Liquid Chromatography Electrospray Ionization Tandem Ma...
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MDPI AG
2022-12-01
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| author | Muqeet Wahid Fatima Saqib Anam Ali Abdulrahman Alshammari Metab Alharbi Abdur Rauf Mohammad S. Mubarak |
| author_facet | Muqeet Wahid Fatima Saqib Anam Ali Abdulrahman Alshammari Metab Alharbi Abdur Rauf Mohammad S. Mubarak |
| author_sort | Muqeet Wahid |
| collection | DOAJ |
| description | The present study aimed to determine the mechanisms responsible for calcium–mediated smooth muscle contractions in <i>C. melo</i> seeds. The phytochemicals of <i>C. melo</i> were identified and quantified with the aid of Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometric (LC/ESI–MS/MS) and high–performance liquid chromatography (HPLC), and then tested in–vitro and in vivo to confirm involvement in smooth muscle relaxation. Allergic asthma gene datasets were acquired from the NCBI gene expression omnibus (GEO) and differentially expressed gene (DEG) analysis, weighted gene co–expression network analysis (WGCNA), and functional enrichment analysis were conducted. Additionally, molecular docking of key genes was carried out. Kaempferol, rutin, and quercetin are identified as phytochemical constituents of <i>C. melo</i> seeds. Results indicated that <i>C. melo</i> seeds exhibit a dose–dependent relaxant effect for potassium chloride (80 mM)– induced spastic contraction and calcium antagonistic response in calcium dose–response curves. The functional enrichment of WGCNA and DEG asthma–associated pathogenic genes showed cytokine–mediated pathways and inflammatory responses. Furthermore, CACNA1A, IL2RB, and NOS2 were identified as key genes with greater binding affinity with rutin, quercitrin, and kaempferol in molecular docking. These results show that the bronchodilator and antidiarrheal effects of <i>C. melo</i> were produced by altering the regulatory genes of calcium–mediated smooth muscle contraction. |
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| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T15:59:45Z |
| publishDate | 2022-12-01 |
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| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-dd21b90df94f48e5add7acf577044e2b2023-11-24T17:16:38ZengMDPI AGPharmaceuticals1424-82472022-12-011512152210.3390/ph15121522Integrated Mechanisms of Polarity–Based Extracts of <i>Cucumis melo</i> L. Seed Kernels for Airway Smooth Muscle Relaxation via Key Signaling Pathways Based on WGCNA, In Vivo, and In Vitro AnalysesMuqeet Wahid0Fatima Saqib1Anam Ali2Abdulrahman Alshammari3Metab Alharbi4Abdur Rauf5Mohammad S. Mubarak6Department of Pharmacology, Faculty of Pharmacy, Bahauddin Zakariya University, Multan 60000, PakistanDepartment of Pharmacology, Faculty of Pharmacy, Bahauddin Zakariya University, Multan 60000, PakistanDepartment of Pharmacology, Faculty of Pharmacy, Bahauddin Zakariya University, Multan 60000, PakistanDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Post Box 2455, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Post Box 2455, Riyadh 11451, Saudi ArabiaDepartment of Chemistry, University of Swabi, Swabi 94640, PakistanDepartment of Chemistry, The University of Jordan, Amma 11942, JordanThe present study aimed to determine the mechanisms responsible for calcium–mediated smooth muscle contractions in <i>C. melo</i> seeds. The phytochemicals of <i>C. melo</i> were identified and quantified with the aid of Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometric (LC/ESI–MS/MS) and high–performance liquid chromatography (HPLC), and then tested in–vitro and in vivo to confirm involvement in smooth muscle relaxation. Allergic asthma gene datasets were acquired from the NCBI gene expression omnibus (GEO) and differentially expressed gene (DEG) analysis, weighted gene co–expression network analysis (WGCNA), and functional enrichment analysis were conducted. Additionally, molecular docking of key genes was carried out. Kaempferol, rutin, and quercetin are identified as phytochemical constituents of <i>C. melo</i> seeds. Results indicated that <i>C. melo</i> seeds exhibit a dose–dependent relaxant effect for potassium chloride (80 mM)– induced spastic contraction and calcium antagonistic response in calcium dose–response curves. The functional enrichment of WGCNA and DEG asthma–associated pathogenic genes showed cytokine–mediated pathways and inflammatory responses. Furthermore, CACNA1A, IL2RB, and NOS2 were identified as key genes with greater binding affinity with rutin, quercitrin, and kaempferol in molecular docking. These results show that the bronchodilator and antidiarrheal effects of <i>C. melo</i> were produced by altering the regulatory genes of calcium–mediated smooth muscle contraction.https://www.mdpi.com/1424-8247/15/12/1522<i>Cucumis melo</i>asthmaairway smooth muscleWGCNALC/ESI–MS/MScalcium–mediated smooth muscle contraction |
| spellingShingle | Muqeet Wahid Fatima Saqib Anam Ali Abdulrahman Alshammari Metab Alharbi Abdur Rauf Mohammad S. Mubarak Integrated Mechanisms of Polarity–Based Extracts of <i>Cucumis melo</i> L. Seed Kernels for Airway Smooth Muscle Relaxation via Key Signaling Pathways Based on WGCNA, In Vivo, and In Vitro Analyses Pharmaceuticals <i>Cucumis melo</i> asthma airway smooth muscle WGCNA LC/ESI–MS/MS calcium–mediated smooth muscle contraction |
| title | Integrated Mechanisms of Polarity–Based Extracts of <i>Cucumis melo</i> L. Seed Kernels for Airway Smooth Muscle Relaxation via Key Signaling Pathways Based on WGCNA, In Vivo, and In Vitro Analyses |
| title_full | Integrated Mechanisms of Polarity–Based Extracts of <i>Cucumis melo</i> L. Seed Kernels for Airway Smooth Muscle Relaxation via Key Signaling Pathways Based on WGCNA, In Vivo, and In Vitro Analyses |
| title_fullStr | Integrated Mechanisms of Polarity–Based Extracts of <i>Cucumis melo</i> L. Seed Kernels for Airway Smooth Muscle Relaxation via Key Signaling Pathways Based on WGCNA, In Vivo, and In Vitro Analyses |
| title_full_unstemmed | Integrated Mechanisms of Polarity–Based Extracts of <i>Cucumis melo</i> L. Seed Kernels for Airway Smooth Muscle Relaxation via Key Signaling Pathways Based on WGCNA, In Vivo, and In Vitro Analyses |
| title_short | Integrated Mechanisms of Polarity–Based Extracts of <i>Cucumis melo</i> L. Seed Kernels for Airway Smooth Muscle Relaxation via Key Signaling Pathways Based on WGCNA, In Vivo, and In Vitro Analyses |
| title_sort | integrated mechanisms of polarity based extracts of i cucumis melo i l seed kernels for airway smooth muscle relaxation via key signaling pathways based on wgcna in vivo and in vitro analyses |
| topic | <i>Cucumis melo</i> asthma airway smooth muscle WGCNA LC/ESI–MS/MS calcium–mediated smooth muscle contraction |
| url | https://www.mdpi.com/1424-8247/15/12/1522 |
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