{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:49:49Z","timestamp":1791355789989,"version":"4.3.1"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Rheumatoid arthritis (RA) is a chronic condition characterized by the infiltration of immune and inflammatory cells into the synovial membranes, which often leads to severe damage to cartilage and bone. In spite of their efficacy, drug-based therapies produce severe side effects. Therefore, there remains an unmet need for non-pharmacological treatments with a low toxicity profile and limited costs. Propolis has been used since ancient times for the treatment of wounds, ulcers, infections, eczemas, myalgia, and rheumatism. Similarly, the traditional use of all parts of pomegranate (\n                      <jats:italic>Punica granatum<\/jats:italic>\n                      L.) is documented across Egyptian, Persian, and Chinese cultures for the treatment of infections and inflammations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This study aimed at the development of preparations containing bioactive compounds derived from propolis and pomegranate peels, inspired by traditional recipes used in rural areas of southern Italy, to validate their efficacy in counteracting the inflammation associated with RA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>A preliminary screening led to the selection of the most promising preparation, composed by propolis and pomegranate peel extracts in a ratio 1:2 (Pp1:2). It underwent a complete chemical characterization by both qualitative and quantitative LC-MS analyses and was tested on a collagen-induced arthritis (CIA) mouse model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vitro<\/jats:italic>\n                      tests showed that Pp1:2 treatment of M1 stimulated by LPS\/IFN\u03b3 reduces cell polarization; furthermore, it reverts the pro-inflammatory effects induced by IL-1\u03b2 on synoviocytes.\n                      <jats:italic>In vivo<\/jats:italic>\n                      experiments, conducted by administering Pp1:2 orally to a suitable murine model, confirmed the ability of the preparation to reduce sensibly RA-like inflammatory effects, as inferred by the change observed in mice paws volume and other RA-related parameters. Furthermore, histological analyses revealed a reduction in the number of M1 macrophages in mice paws following Pp1:2 treatment, and an attenuation of the pathological remodeling of collagen IV and of ICAM-1 expression, compared to untreated controls.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1910652","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:53:29Z","timestamp":1791352409000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A mixture of pomegranate peels and propolis extracts reduces inflammation associated with rheumatoid arthritis in vivo"],"prefix":"10.3389","volume":"17","author":[{"given":"Maria Laura","family":"Bellone","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Salerno","place":["Fisciano, Italy"]},{"name":"Department of Medicine, Surgery and Dentistry, University of Salerno","place":["Baronissi, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela Carmelita","family":"Abate","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry, University of Salerno","place":["Baronissi, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Di Pietro","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry, University of Salerno","place":["Baronissi, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Parisi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno","place":["Fisciano, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"D\u2019Angiolo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa","place":["Pisa, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Prosperi","sequence":"additional","affiliation":[{"name":"Animal Facility Unit, Biogem","place":["Ariano Irpino, Avellino, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Pisano","sequence":"additional","affiliation":[{"name":"Animal Facility Unit, Biogem","place":["Ariano Irpino, Avellino, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albino","family":"Carrizzo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry, University of Salerno","place":["Baronissi, Italy"]},{"name":"Vascular Physiopathology Unit, IRCCS Neuromed","place":["Pozzilli, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Braca","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa","place":["Pisa, Italy"]},{"name":"Center for Instrument Sharing University of Pisa (CISUP), University of Pisa","place":["Pisa, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio Dal","family":"Piaz","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry, University of Salerno","place":["Baronissi, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marinella","family":"De Leo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa","place":["Pisa, Italy"]},{"name":"Center for Instrument Sharing University of Pisa (CISUP), University of Pisa","place":["Pisa, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nunziatina","family":"De Tommasi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno","place":["Fisciano, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1002\/BIOF.1199","article-title":"Pomegranate juice polyphenols induce a phenotypic switch in macrophage polarization favoring a M2 anti-inflammatory state","volume":"41","author":"Aharoni","year":"2015","journal-title":"Biofactors"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2589","DOI":"10.1002\/FSN3.3320","article-title":"Nutritional importance and industrial uses of pomegranate peel: a critical review","volume":"11","author":"Ain","year":"2023","journal-title":"Food Sci. 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