{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T14:04:42Z","timestamp":1770818682108,"version":"3.50.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T00:00:00Z","timestamp":1697068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold> Hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) is emerging as an important potential therapeutic option for respiratory inflammatory diseases. In this study, we investigated the effectiveness of a novel corticosteroid derivative, that is chemically linked to an H<jats:sub>2<\/jats:sub>S donor, in managing asthma features.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> The effects of prednisone (PS), H<jats:sub>2<\/jats:sub>S donor (4-hydroxybenzamide; TBZ), and their combination (PS-TBZ) have been evaluated <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. The <jats:italic>in vitro<\/jats:italic> experiments were conducted using lipopolysaccharidestimulated J774 macrophages, while the <jats:italic>in vivo<\/jats:italic> experiments utilizing an experimental asthma model.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> In the <jats:italic>in vitro<\/jats:italic> study we found that PS-TBZ exhibited an increased effect compared to the individual parent compounds in modulating the production of inflammatory mediators. TBZ also significantly reduced bronchial contractility and enhanced bronchial relaxation. In the <jats:italic>in vivo<\/jats:italic> experiments, where we administered PS, TBZ, or PS-TBZ to ovalbumin-sensitized BALB\/c mice, we confirmed that PS-TBZ had a significantly better action in controlling airway hyperreactivity as compared to TBZ or PS alone. Moreover, PS-TBZ was more effective in restoring salbutamol-induced relaxation. The immunohistochemistry analysis demonstrated a significant reduction in the production of \u03b1-SMA and procollagen III, indicating the efficacy of PS-TBZ in controlling airway remodeling. Moreover, PS-TBZ also promoted epithelial repair, recovery of the bronchial and parenchyma structure and inhibited mucin production.<\/jats:p><jats:p><jats:bold>Discussion:<\/jats:bold> In conclusion, PS-TBZ offers an important opportunity to optimize the beneficial impact of corticosteroids on asthma features.<\/jats:p>","DOI":"10.3389\/fphar.2023.1266934","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T16:33:54Z","timestamp":1697128434000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Prednisone-hydrogen sulfide releasing hybrid shows improved therapeutic profile in asthma"],"prefix":"10.3389","volume":"14","author":[{"given":"Ida","family":"Cerqua","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabetta","family":"Granato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Corvino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrice","family":"Severino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danilo","family":"D\u2019Avino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Simonelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Perissutti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonia","family":"Scognamiglio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davida","family":"Mirra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"D\u2019Agostino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Caliendo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonietta","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Cirino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara Maria","family":"Motta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiorentina","family":"Roviezzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"187","DOI":"10.4103\/1817-1737.140120","article-title":"Corticosteroids in the treatment of acute asthma","volume":"9","author":"Alangari","year":"2014","journal-title":"Ann. 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