{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T23:40:17Z","timestamp":1792885217659,"version":"4.5.0"},"reference-count":59,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoX"],"abstract":"<jats:p>Although praziquantel (PZQ) is the main antischistosomal drug currently in use, concerns remain regarding incomplete reversal of schistosomiasis-induced pathology and the emergence of drug resistance. This study evaluates the combined effect of PZQ with safranal, a bioactive saffron constituent, on Schistosoma mansoni-induced pathology in mice. Male CD1 Swiss albino mice were exposed to 60 S. mansoni cercariae and, at week 9 post-infection, were treated with PZQ (500 mg\/kg orally for two consecutive days), safranal (50 mg\/kg\/day), or both, for three weeks. The animals were sacrificed at week 11 post-infection. Worm and egg burdens, liver histopathology, fibrotic markers, oxidative stress, and inflammatory cytokines were assessed. Combined PZQ + safranal therapy significantly reduced adult worm counts and hepatic and intestinal egg loads compared to PZQ alone. All treatments decreased liver index (hepatomegaly), with the combination treatment providing the best intervention. Histological analyses revealed significantly reduced granuloma size and hepatic necrosis post-treatment, particularly in the combination group. The levels of proinflammatory cytokines (TNF-\u03b1, IL-1\u03b2) and Th2 cytokines (IL-4, IL-5, IL-6, IL-10) were significantly lowered in treated mice, most notably with the combination treatment. Oxidative stress was also markedly attenuated, and infected mice exhibited elevated malondialdehyde and depleted antioxidant enzymes (SOD, CAT, GSH). Interestingly, PZQ and\/or safranal restored antioxidant status and reduced lipid peroxidation, with the combination being most effective. Furthermore, collagen deposition and expression of hepatic fibrotic markers \u03b1-smooth muscle actin (\u03b1-SMA), TGF-\u03b21, and matrix metalloproteinase-9 were most effectively suppressed by combined therapy. To conclude, safranal enhances PZQ\u2019s antischistosomal efficacy and confers additive protection against Schistosoma-induced liver fibrosis.<\/jats:p>","DOI":"10.3390\/jox16040120","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:54:42Z","timestamp":1782694482000},"page":"120","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Safranal Enhances the Efficacy of Praziquantel Against Schistosoma mansoni Infection and Alleviates Liver Fibrosis, Inflammation and Oxidative Stress in Mice"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4891-3357","authenticated-orcid":false,"given":"Azza","family":"Fahmy","sequence":"first","affiliation":[{"name":"Departments of Parasitology, Immunology & Drug Evaluation, Theodor Bilharz Research Institute, Giza 12411, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amany Mohammed Mohmmed","family":"Hegab","sequence":"additional","affiliation":[{"name":"Developmental Pharmacology and Acute Toxicity Department, Egyptian Drug Authority (EDA), Formerly National Organization of Drug Control and Research, Giza 12112, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanan S.","family":"Mossalem","sequence":"additional","affiliation":[{"name":"Medical Malacology Department, Theodor Bilharz Research Institute, Giza 12411, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8189-5998","authenticated-orcid":false,"given":"Samah Sulaiman","family":"Abuzahrah","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Science, University of Jeddah, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saud Omar","family":"Alafghani","sequence":"additional","affiliation":[{"name":"Department of Histopathology, Al Hada Military Hospital, Taif 26792, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5450-1116","authenticated-orcid":false,"given":"Alaaeldin Ahmed","family":"Hamza","sequence":"additional","affiliation":[{"name":"Biology Department, Egyptian Drug Authority (EDA), Formerly National Organization of Drug Control and Research (NODCAR), Giza 12611, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nouf","family":"Juaid","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Science, Inaya Medical College, Riyadh 12211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8888-1102","authenticated-orcid":false,"given":"Amr","family":"Amin","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Diego, J.G.-B., Fern\u00e1ndez-Soto, P., and Muro, A. 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