{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:10:51Z","timestamp":1791933051966,"version":"4.3.4"},"reference-count":94,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T00:00:00Z","timestamp":1695340800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Slovak Grant Agency","award":["VEGA No. 2\/0136\/20"],"award-info":[{"award-number":["VEGA No. 2\/0136\/20"]}]},{"name":"Slovak Grant Agency","award":["VEGA No. 2\/0091\/23"],"award-info":[{"award-number":["VEGA No. 2\/0091\/23"]}]},{"name":"Slovak Grant Agency","award":["VEGA No. 2\/0126\/23"],"award-info":[{"award-number":["VEGA No. 2\/0126\/23"]}]},{"name":"Slovak Grant Agency","award":["VEGA No. 1\/0429\/21"],"award-info":[{"award-number":["VEGA No. 1\/0429\/21"]}]},{"name":"Slovak Grant Agency","award":["APVV-15-0308"],"award-info":[{"award-number":["APVV-15-0308"]}]},{"name":"Ministry of Education, Science, Research and Sport of the Slovak Republic","award":["VEGA No. 2\/0136\/20"],"award-info":[{"award-number":["VEGA No. 2\/0136\/20"]}]},{"name":"Ministry of Education, Science, Research and Sport of the Slovak Republic","award":["VEGA No. 2\/0091\/23"],"award-info":[{"award-number":["VEGA No. 2\/0091\/23"]}]},{"name":"Ministry of Education, Science, Research and Sport of the Slovak Republic","award":["VEGA No. 2\/0126\/23"],"award-info":[{"award-number":["VEGA No. 2\/0126\/23"]}]},{"name":"Ministry of Education, Science, Research and Sport of the Slovak Republic","award":["VEGA No. 1\/0429\/21"],"award-info":[{"award-number":["VEGA No. 1\/0429\/21"]}]},{"name":"Ministry of Education, Science, Research and Sport of the Slovak Republic","award":["APVV-15-0308"],"award-info":[{"award-number":["APVV-15-0308"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Rheumatoid arthritis (RA), an autoimmune disease, is characterized by inflammation that affects not only the liver but also other organs and the musculoskeletal system. The standard therapy for RA is methotrexate (MTX), which has safety limitations. The extract from Crocus sativus L. (saffron\u2014SF) is also known for its anti-inflammatory effects. Therefore, we decided to investigate the potential benefit of SF in monotherapy via two doses (SF1\u201425 mg\/kg of b.w.; SF2\u201450 mg\/kg of b.w.) and in combination with MTX (0.3 mg\/kg of b.w., twice a week) using adjuvant arthritis in rats. To evaluate these therapeutic settings, we used biometric, immunological, and biochemical parameters, as well as the relative gene expression of the mRNA in the liver. Our results showed a statistically significant increase in the experimental animals\u2019 body weight and the arthritic score (AS) on day 14 for monotherapy with SF1 and SF2. The change of hind paw volume (CHPV) was significant only for SF2 monotherapy on the 14th day of the experiment. A combination of SF1 and SF2 with MTX significantly modulated all the biometric parameters during the experimental period. Additionally, AS and CHPV improved considerably compared to MTX monotherapy on day 21. Furthermore, all monotherapies and combination therapies were significant for the biochemical parameter \u03b3-glutamyl transferase (GGT) in the joint. GGT activity in the spleen was less pronounced; only MTX in combination with SF1 significantly modified this parameter. The higher dose of SF monotherapy (SF2) was similarly significant with respect to immunological parameters, such as plasmatic IL-17A, IL-1\u03b2, and MMP-9 on day 21. The combination of both doses of SF with MTX significantly improved these immunological parameters, except for C-reactive protein (CRP), which was influenced only by the higher dose of SF2 in combination with MTX in plasma at the end of the experiment. A different effect was found for the relative expression of CD36 mRNA, where only SF1 significantly decreased gene expression in the liver. However, the relative gene mRNA expression of IL-1\u03b2 in the liver was significantly reduced by the SF monotherapies and the combination of both SF doses with MTX. Our findings showed SF\u2019s partial antiarthritic and anti-inflammatory potential in monotherapy, but the effect was stronger in combination with MTX.<\/jats:p>","DOI":"10.3390\/nu15194108","type":"journal-article","created":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T10:46:21Z","timestamp":1695552381000},"page":"4108","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Crocus sativus L. Extract (Saffron) Effectively Reduces Arthritic and Inflammatory Parameters in Monotherapy and in Combination with Methotrexate in Adjuvant Arthritis"],"prefix":"10.3390","volume":"15","author":[{"given":"Martin","family":"Chrastina","sequence":"first","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology, Centre of Experimental Medicine SAS, 841 04 Bratislava, Slovakia"},{"name":"Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mal\u00e1 Hora 10701\/4A, 036 01 Martin, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9287-5514","authenticated-orcid":false,"given":"Franti\u0161ek","family":"Dr\u00e1fi","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology, Centre of Experimental Medicine SAS, 841 04 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katar\u00edna","family":"Pru\u017einsk\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology, Centre of Experimental Medicine SAS, 841 04 Bratislava, Slovakia"},{"name":"Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mal\u00e1 Hora 10701\/4A, 036 01 Martin, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9672-5441","authenticated-orcid":false,"given":"Silvester","family":"Poni\u0161t","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology, Centre of Experimental Medicine SAS, 841 04 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9080-7905","authenticated-orcid":false,"given":"Kevine Silihe","family":"Kamga","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology, Centre of Experimental Medicine SAS, 841 04 Bratislava, Slovakia"},{"name":"Faculty of Science, University of Yaound\u00e9 1, Yaound\u00e9 P.O. Box 812, Cameroon"},{"name":"Faculty of Medicine and Biomedical Sciences, University of Yaound\u00e9 1, Yaound\u00e9 P.O. Box 1364, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasan","family":"Khademnematolahi","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology, Centre of Experimental Medicine SAS, 841 04 Bratislava, Slovakia"},{"name":"Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovi\u010dova 6, 842 15 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franti\u0161ek","family":"Bilka","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Comenius University in Bratislava, Odboj\u00e1rov 10, 832 32 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Nov\u00e1k","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Comenius University in Bratislava, Odboj\u00e1rov 10, 832 32 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8732-7054","authenticated-orcid":false,"given":"\u013dudmila","family":"Pa\u0161kov\u00e1","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Comenius University in Bratislava, Odboj\u00e1rov 10, 832 32 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7863-2142","authenticated-orcid":false,"given":"Katar\u00edna","family":"Bauerov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology, Centre of Experimental Medicine SAS, 841 04 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/s41581-023-00720-1","article-title":"Pathogenesis of autoimmune disease","volume":"19","author":"Pisetsky","year":"2023","journal-title":"Nat. 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