{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T12:46:22Z","timestamp":1765889182177,"version":"build-2065373602"},"reference-count":88,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T00:00:00Z","timestamp":1696464000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Paraiba State University","award":["#02\/2023"],"award-info":[{"award-number":["#02\/2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The N-acylhydrazone function has been reported as a pharmacophore group of molecules with diverse pharmacological activities, including anti-inflammatory effects. Therefore, this study was designed to evaluate the anti-inflammatory potential of the compound N\u2032-(3-(1H-indol-3-yl)benzylidene)-2-cyanoacetohydrazide (JR19) in vivo. The study started with the carrageenan-induced peritonitis model, followed by an investigation of leukocyte migration using the subcutaneous air pouch test and an assessment of the antinociceptive profile using formalin-induced pain. A preliminary molecular docking study focusing on the crystallographic structures of NF\u03baB, iNOS, and sGC was performed to determine the likely mechanism of action. The computational study revealed satisfactory interaction energies with the selected targets, and the same peritonitis model was used to validate the involvement of the nitric oxide pathway and cytokine expression in the peritoneal exudate of mice pretreated with L-NAME or methylene blue. In the peritonitis assay, JR19 (10 and 20 mg\/kg) reduced leukocyte migration by 59% and 52%, respectively, compared to the vehicle group, with the 10 mg\/kg dose used in subsequent assays. In the subcutaneous air pouch assay, the reduction in cell migration was 66%, and the response to intraplantar formalin was reduced by 39%, particularly during the inflammatory phase, suggesting that the compound lacks central analgesic activity. In addition, a reversal of the anti-inflammatory effect was observed in mice pretreated with L-NAME or methylene blue, indicating the involvement of iNOS and sGC in the anti-inflammatory response of JR19. The compound effectively and significantly decreased the levels of IL-6, TNF-\u03b1, IL-17, and IFN-\u03b3, and this effect was reversed in animals pretreated with L-NAME, supporting a NO-dependent anti-inflammatory effect. In contrast, pretreatment with methylene blue only reversed the reduction in TNF-\u03b1 levels. Therefore, these results demonstrate the pharmacological potential of the novel N-acylhydrazone derivative, which acts through the nitric oxide pathway and cytokine signaling, making it a strong candidate as an anti-inflammatory and immunomodulatory agent.<\/jats:p>","DOI":"10.3390\/ph16101415","type":"journal-article","created":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T03:05:19Z","timestamp":1696475119000},"page":"1415","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Anti-Inflammatory Activity of N\u2032-(3-(1H-indol-3-yl)benzylidene)-2-cyanoacetohydrazide Derivative via sGC-NO\/Cytokine Pathway"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8354-3198","authenticated-orcid":false,"given":"Pablo Rayff","family":"da Silva","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Estadual da Para\u00edba, Campina Grande 58429-500, PB, Brazil"},{"name":"Laborat\u00f3rio de Ensaios Farmacol\u00f3gicos, Departamento de Farm\u00e1cia, Universidade Estadual da Para\u00edba, Campina Grande 58429-500, PB, Brazil"},{"name":"Laborat\u00f3rio de Desenvolvimento e S\u00edntese de F\u00e1rmacos, Departamento de Farm\u00e1cia, Universidade Estadual da Para\u00edba, Campina Grande 58429-500, PB, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadjaele de Melo","family":"Apolin\u00e1rio","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Estadual da Para\u00edba, Campina Grande 58429-500, PB, Brazil"},{"name":"Laborat\u00f3rio de Ensaios Farmacol\u00f3gicos, Departamento de Farm\u00e1cia, Universidade Estadual da Para\u00edba, Campina Grande 58429-500, PB, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone \u00c2ngela Soares da","family":"Silva","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Estadual da Para\u00edba, Campina Grande 58429-500, PB, Brazil"},{"name":"Laborat\u00f3rio de Ensaios Farmacol\u00f3gicos, Departamento de Farm\u00e1cia, Universidade Estadual da Para\u00edba, Campina Grande 58429-500, PB, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Elaine Cristina","family":"Araruna","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Estadual da Para\u00edba, Campina Grande 58429-500, PB, Brazil"},{"name":"Laborat\u00f3rio de Ensaios Farmacol\u00f3gicos, Departamento de Farm\u00e1cia, Universidade Estadual da Para\u00edba, Campina Grande 58429-500, PB, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Th\u00e1ssia Borges","family":"Costa","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Estadual da Para\u00edba, Campina Grande 58429-500, PB, Brazil"},{"name":"Laborat\u00f3rio de Ensaios Farmacol\u00f3gicos, Departamento de Farm\u00e1cia, Universidade Estadual da Para\u00edba, Campina Grande 58429-500, PB, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yvnni M. S. de Medeiros","family":"e Silva","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Estadual da Para\u00edba, Campina Grande 58429-500, PB, Brazil"},{"name":"Laborat\u00f3rio de Desenvolvimento e S\u00edntese de F\u00e1rmacos, Departamento de Farm\u00e1cia, Universidade Estadual da Para\u00edba, Campina Grande 58429-500, PB, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresinha Gon\u00e7alves","family":"da Silva","sequence":"additional","affiliation":[{"name":"Departamento de Antibi\u00f3ticos, Centro de Bioci\u00eancias, Universidade Federal de Pernambuco, Recife 50740-520, PE, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1590-3750","authenticated-orcid":false,"given":"Ricardo Ol\u00edmpio","family":"de Moura","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Estadual da Para\u00edba, Campina Grande 58429-500, PB, Brazil"},{"name":"Laborat\u00f3rio de Desenvolvimento e S\u00edntese de F\u00e1rmacos, Departamento de Farm\u00e1cia, Universidade Estadual da Para\u00edba, Campina Grande 58429-500, PB, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6083-5390","authenticated-orcid":false,"given":"Vanda Lucia","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Estadual da Para\u00edba, Campina Grande 58429-500, PB, Brazil"},{"name":"Laborat\u00f3rio de Ensaios Farmacol\u00f3gicos, Departamento de Farm\u00e1cia, Universidade Estadual da Para\u00edba, Campina Grande 58429-500, PB, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Fikry, E.M., Hasan, W.A., and Mohamed, E.G. 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