{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T13:10:40Z","timestamp":1779973840455,"version":"3.53.1"},"reference-count":86,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":147,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004242","name":"Princess Nourah Bint Abdulrahman University","doi-asserted-by":"publisher","award":["PNURSP2026R37"],"award-info":[{"award-number":["PNURSP2026R37"]}],"id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Rheumatoid arthritis (RA) is a long\u2010term inflammatory disease linked to higher mortality, joint degeneration, and long\u2010term disability. This study evaluated the anti\u2010inflammatory, antioxidant, and immunomodulatory effects of\n                      <jats:italic>Capsicum annuum<\/jats:italic>\n                      (CAP) hydroethanolic extract and bee venom (BV) in Freund\u2019s complete adjuvant (FCA)\u2010induced RA in rats.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Forty\u2010eight rats were divided into six groups: normal control (NC), RA control, and RA groups orally treated with methotrexate (MTX) (0.25\u2009mg\/kg), CAP (100\u2009mg\/kg), BV (0.25\u2009mg\/kg), and CAP (100\u2009mg\/kg)\u2009+\u2009BV (0.25\u2009mg\/kg). RA was induced by intradermal injection of FCA (100\u2009\u03bcL\/rat) into a footpad of the right hind paw at two consecutive days, and treatments were administered for 3 weeks. The study assessed serum rheumatoid factor (RF), anticyclic citrullinated peptide (ACCP) antibodies (ACPAs), tumor necrosis factor\u2010alpha (TNF\u2010\u03b1), interleukin\u20104 (IL\u20104), oxidative stress markers such as lipid peroxidation, and antioxidant parameters including superoxide dismutase (SOD) and reduced glutathione (GSH). Additionally, mRNA expression of various genes (inducible nitric oxide synthase [\n                      <jats:italic>iNOS<\/jats:italic>\n                      ], endothelial nitric oxide synthase [\n                      <jats:italic>eNOS<\/jats:italic>\n                      ], interleukin\u20101\u03b2 [\n                      <jats:italic>IL-1\u03b2<\/jats:italic>\n                      ],\n                      <jats:italic>TNF-\u03b1<\/jats:italic>\n                      , matrix metalloproteinase\u20101 [\n                      <jats:italic>MMP-1<\/jats:italic>\n                      ], matrix metalloproteinase\u20103 [\n                      <jats:italic>MMP-3<\/jats:italic>\n                      ], and glutathione reductase [\n                      <jats:italic>GR<\/jats:italic>\n                      ]) were analyzed, alongside histopathological evaluation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The data showed that CAP and\/or BV significantly reduced serum inflammatory and oxidative stress biomarkers, enhanced the antioxidant defense system, and improved the histopathological changes of ankle joint. Gene expression analysis revealed downregulation of\n                      <jats:italic>iNOS<\/jats:italic>\n                      ,\n                      <jats:italic>eNOS<\/jats:italic>\n                      ,\n                      <jats:italic>IL-1\u03b2<\/jats:italic>\n                      ,\n                      <jats:italic>TNF-\u03b1<\/jats:italic>\n                      ,\n                      <jats:italic>MMP-1<\/jats:italic>\n                      , and\n                      <jats:italic>MMP-3<\/jats:italic>\n                      gene expression, with upregulation of the\n                      <jats:italic>GR<\/jats:italic>\n                      gene expression. The combined CAP\u2009+\u2009BV treatment demonstrated the most potent antiarthritic effect.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      CAP and BV exhibit promising potential for alleviating RA in rats, with their combined application showing the greatest efficacy. The antiarthritic effects may be mediated via suppression of oxidative stress and inflammation and enhancement of the antioxidant defense system in addition to the modulatory effects on\n                      <jats:italic>MMP-1<\/jats:italic>\n                      and\n                      <jats:italic>MMP-3<\/jats:italic>\n                      gene expression. Further clinical research is essential to evaluate their safety and effectiveness in human RA management.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/mi\/5550872","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T12:29:42Z","timestamp":1779971382000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic Potential of Bee Venom and\n                    <i>Capsicum annum<\/i>\n                    Hydroethanolic Extract in Experimental Model of Rheumatoid Arthritis in Male Rats"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3416-2115","authenticated-orcid":false,"given":"Ahmed","family":"Hussain","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1722-2569","authenticated-orcid":false,"given":"Amira Sh.","family":"Soliman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5879-7022","authenticated-orcid":false,"given":"Mohamed","family":"Abd-Elbaset","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9278-0822","authenticated-orcid":false,"given":"Areej A.","family":"Al-Khalf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7165-3573","authenticated-orcid":false,"given":"Eman A.","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6529-5645","authenticated-orcid":false,"given":"Abdelwahab","family":"Khalil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3781-9709","authenticated-orcid":false,"given":"Osama M.","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1045-384X","authenticated-orcid":false,"given":"Mohamed S.","family":"Abbas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.5114\/reum\/168503"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/1541-4337.12634"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2019.02.016"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7258(02)00166-3"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms221910576"},{"key":"e_1_2_12_6_2","doi-asserted-by":"crossref","first-page":"v3","DOI":"10.1093\/rheumatology\/kes113","article-title":"Understanding the Dynamics: Pathways Involved in the Pathogenesis of Rheumatoid Arthritis","volume":"51","author":"Choy E.","year":"2012","journal-title":"Rheumatology"},{"key":"e_1_2_12_7_2","first-page":"439","article-title":"A Review of the Effects of Capsicum Annuum L. 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