{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:58:39Z","timestamp":1787029119921,"version":"build-2736575974"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,16]],"date-time":"2025-02-16T00:00:00Z","timestamp":1739664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FIOCRUZ"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The dysregulation of immune responses are responsible for the development of several diseases, such as allergic and autoimmune diseases. The medications used to treat these conditions have numerous side effects, creating the need for new drugs. Physalins are natural compounds with various pharmacological activities already described. Here, we aimed to investigate the immunomodulatory effects of physalin F in mouse splenocytes and in a delayed-type hypersensitivity (DTH) model. In a cytotoxicity assay, physalin F had low cytotoxicity to mouse splenocytes in concentrations equal to or below 2 \u00b5M. It significantly inhibited lymphocyte proliferation in a concentration-dependent manner and reduced the production of cytokines, including IL-2, IL-4, IL-10, and IFN-\u03b3, in activated splenocytes. The combined therapy of physalin F with dexamethasone was investigated in vitro, showing a synergistic action of the two compounds. Mechanistically, physalin F reduced calcineurin activity in concanavalin A-stimulated splenocyte cultures. Finally, in vivo, the intraperitoneal administration of physalin F in a DTH model reduced paw edema induced by bovine serum albumin immunization. Our results demonstrate the potential of physalin F as an immunosuppressive agent, to be used alone or in combination with glucocorticoids.<\/jats:p>","DOI":"10.3390\/molecules30040916","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T12:36:57Z","timestamp":1739795817000},"page":"916","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Physalin F, a Potent Inhibitor of Lymphocyte Function, Is a Calcineurin Inhibitor and Has Synergistic Effect with Dexamethasone"],"prefix":"10.3390","volume":"30","author":[{"given":"Dahara Keyse Carvalho","family":"Silva","sequence":"first","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador 40296-710, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Beatriz da Cruz","family":"Novo","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador 40296-710, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivone Maria","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Laboratory of Natural Products Chemistry\u2014PN2, Farmanguinhos, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 22775-903, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Breno Cardim","family":"Barreto","sequence":"additional","affiliation":[{"name":"Institute for Innovation in Advanced Health Systems, National Service for Industrial Learning\u2014Integrated Center for Manufacturing and Technology (SENAI CIMATEC), Salvador 41650-010, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7941-6855","authenticated-orcid":false,"given":"Luiza Carolina Fran\u00e7a","family":"Opretzka","sequence":"additional","affiliation":[{"name":"Institute for Innovation in Advanced Health Systems, National Service for Industrial Learning\u2014Integrated Center for Manufacturing and Technology (SENAI CIMATEC), Salvador 41650-010, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e1ssio Santana","family":"Meira","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador 40296-710, BA, Brazil"},{"name":"Institute for Innovation in Advanced Health Systems, National Service for Industrial Learning\u2014Integrated Center for Manufacturing and Technology (SENAI CIMATEC), Salvador 41650-010, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena Botelho Pereira","family":"Soares","sequence":"additional","affiliation":[{"name":"Gon\u00e7alo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador 40296-710, BA, Brazil"},{"name":"Institute for Innovation in Advanced Health Systems, National Service for Industrial Learning\u2014Integrated Center for Manufacturing and Technology (SENAI CIMATEC), Salvador 41650-010, BA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1002\/acr.23775","article-title":"Chronic Inflammation in RA: Mediator of Skeletal Muscle Pathology and Physical Impairment","volume":"71","author":"Hanaoka","year":"2019","journal-title":"Arthritis Care Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3097","DOI":"10.1172\/JCI30602","article-title":"TREM-1\u2013Expressing Intestinal Macrophages Crucially Amplify Chronic Inflammation in Experimental Colitis","volume":"117","author":"Schenk","year":"2007","journal-title":"J. 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