{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:32:25Z","timestamp":1778113945855,"version":"3.51.4"},"reference-count":63,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["OMICS: A Journal of Integrative Biology"],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:p>\n                    Conventional pharmacological interventions for erectile dysfunction (ED) primarily rely on the phosphodiesterase-5 (PDE5) inhibitors such as sildenafil, tadalafil, vardenafil, and avanafil that have side effects despite their therapeutic effects. PDE5 is the primary cyclic guanosine monophosphate-degrading enzyme located in the smooth muscles of the corpus cavernosum in the penile tissue that helps in relieving erection. Natural products and phytochemicals are viable sources of molecular leads for drug discovery and development and, thus, offer prospects for innovation in ED treatment. This\n                    <jats:italic toggle=\"yes\">in silico<\/jats:italic>\n                    study reports the screening of phytochemicals from the plant\n                    <jats:italic toggle=\"yes\">Tribulus terrestris<\/jats:italic>\n                    with an eye to identify molecular candidates that inhibit PDE5. Natural products-based compounds that selectively target PDE5 are poised to be useful in clinical management of ED, and potentially with lesser side effects. The following top three phytochemicals identified from\n                    <jats:italic toggle=\"yes\">T. terrestris<\/jats:italic>\n                    showed higher negative binding affinities for the PDE5 enzyme: diosgenin,dehydro (\u221211.1 kcal\/mol), ruscogenin (\u221211.1 kcal\/mol), and hecogenin (\u221210.3 kcal\/mol) compared with the control drug sildenafil (\u22128.8 kcal\/mol). Hydrogen bonds and Van der Waals interactions were the predominant forces influencing the interactions formed in the protein\u2013ligand complexes. The \u0394G\n                    <jats:sub>bind<\/jats:sub>\n                    binding free energies for these top three phytochemicals, diosgenin,dehydro, ruscogenin, and hecogenin, were \u221219.99 \u00b1 5.99 kcal\/mol, \u22129.05 \u00b1 5.16 kcal\/mol, and \u221214.11 \u00b1 5.33 kcal\/mol, respectively. Importantly, diosgenin,dehydro, a saponin obtained from\n                    <jats:italic toggle=\"yes\">T. terrestris<\/jats:italic>\n                    , was identified as a particularly promising candidate for PDE5 inhibition by virtue of its higher negative binding affinity and, therefore, displaying a potential in drug discovery and development for ED. In addition,\n                    <jats:italic toggle=\"yes\">in silico<\/jats:italic>\n                    pharmacokinetic analysis and toxicity assessments support the prospects of these\n                    <jats:italic toggle=\"yes\">T. terrestris<\/jats:italic>\n                    -derived phytochemicals for future\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                    research for innovation in ED therapeutics.\n                  <\/jats:p>","DOI":"10.1177\/15578100251370567","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T17:20:42Z","timestamp":1759944042000},"page":"442-457","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Toward Natural Products-Based Drug Development for Erectile Dysfunction: A Molecular Candidate from Plant\n                    <i>Tribulus terrestris<\/i>\n                    Identified by an Integrated\n                    <i>In Silico<\/i>\n                    Study"],"prefix":"10.1177","volume":"29","author":[{"given":"Riya","family":"Vishwakarma","sequence":"first","affiliation":[{"name":"Centre for Integrative Omics Data Science, Yenepoya (Deemed to be University), Mangalore, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abel John","family":"Koshy","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science, Yenepoya (Deemed to be University), Mangalore, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haritha","family":"Kalath","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science, Yenepoya (Deemed to be University), Mangalore, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krishnapriya","family":"Ramakrishnan","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science, Yenepoya (Deemed to be University), Mangalore, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anish","family":"John","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences, Mangalore, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sowmya","family":"Soman","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science, Yenepoya (Deemed to be University), Mangalore, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2319-121X","authenticated-orcid":false,"given":"Rajesh","family":"Raju","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science, Yenepoya (Deemed to be University), Mangalore, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8015-365X","authenticated-orcid":false,"given":"Niyas","family":"Rehman","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science, Yenepoya (Deemed to be University), Mangalore, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0036-6582","authenticated-orcid":false,"given":"Amjesh","family":"Revikumar","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science, Yenepoya (Deemed to be University), Mangalore, India."},{"name":"Kerala Genome Data Centre, Kerala Development and Innovation Strategic Council, Thiruvananthapuram, India."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,8,29]]},"reference":[{"key":"e_1_3_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2017.07.018"},{"key":"e_1_3_6_3_1","doi-asserted-by":"publisher","DOI":"10.47102\/annals-acadmedsg.V29N1p22"},{"issue":"12","key":"e_1_3_6_4_1","first-page":"e32179","article-title":"A systematic review of sildenafil mortality through the years","volume":"14","author":"Al Ibrahim AH","year":"2022","unstructured":"Al Ibrahim AH, , Ghallab KQ, , Alhumaid FI, et al. 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