RT Journal Article T1 Mechanistic insights of Cucumis melo L. seeds for gastrointestinal muscle spasms through calcium signaling pathway–related gene regulation networks in WGCNA and in vitro, in vivo studies A1 Wahid, Muqeet A1 Saqib, Fatima A1 Akhtar, Saeed A1 Ali, Anam A1 Tallei, Trina Ekawati A1 Simal Gándara, Jesús K1 3309 Tecnología de los Alimentos K1 3309.20 Propiedades de Los Alimentos K1 3205.03 Gastroenterología AB Background: In addition to the nutritional benefits of Cucumis melo L., herbalists in Pakistan and India employseeds to treat various ailments. This study aimed to determine the regulatory role of C. melo seeds in calciummediatedsmooth muscle contraction.Methods: We identified and quantified the phytochemicals of C. melo with LC ESI–MS/MS and HPLC, thenconducted in vitro and in vivo tests to confirm the involvement in smooth muscle relaxation. Then, diarrheapredominantirritable bowel syndrome gene datasets from NCBI GEO were acquired, DEGs and WGCNA followedby functional enrichment analysis. Next, molecular docking of key genes was performed.Results: The quantification of C. melo seeds revealed concentrations of rutin, kaempferol, and quercetin were702.38 μg/g, 686.29 μg/g, and 658.41 μg/g, respectively. In vitro experiments revealed that C. melo seeds had adose-dependent relaxant effect for potassium chloride (80 mM)–induced spastic contraction and exhibited calciumantagonistic response in calcium dose-response curves. In in vivo studies, Cm.EtOH exhibited antidiarrheal,antiperistaltic, and antisecretory effects. The functional enrichment of WGCNA and DEGs IBS-associated pathogenicgenes, including those involved in calcium-mediated signaling, MAPK cascade, and inflammatory responses.MAPK1 and PIK3CG were identified as key genes with greater binding affinity with rutin, quercitrin, andkaempferol in molecular docking.Conclusions: The bronchodilator and antidiarrheal effects of C. melo were produced by altering the regulatorygenes of calcium-mediated smooth contraction PB Computers in Biology and Medicine SN 00104825 YR 2023 FD 2023-03 LK http://hdl.handle.net/11093/4938 UL http://hdl.handle.net/11093/4938 LA eng NO Computers in Biology and Medicine, 155, 106596 (2023) NO Universidade de Vigo/CISUG DS Investigo RD 20-sep-2024