{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T13:28:58Z","timestamp":1786973338492,"version":"build-2736575974"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":228,"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"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Parasitology Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"\n Background<\/jats:title>\n \n Giardiasis continues to be a significant intestinal parasitic infection, with instances of treatment failure and recurrence underscoring the necessity for supplementary therapeutic approaches. Astragaloside (AGS), a bioactive compound known for its anti\u2010inflammatory and immunomodulatory effects, may serve as a promising adjunctive treatment; however, its efficacy against\n Giardia<\/jats:italic>\n infection has not been thoroughly examined. Accordingly, this study aimed to assess the antigiardial efficacy of AGS both as a monotherapy and in combination with metronidazole (METR), focusing specifically on parameters such as parasite cyst burden and viability, intestinal mucosal immune responses, inflammatory markers, and hepatic safety associated with treatment.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n The MTT colorimetric assay was used to evaluate the in vitro antigiardial effects of AGS against\n Giardia<\/jats:italic>\n trophozoites. Mice infected with\n Giardia<\/jats:italic>\n were treated with AGS (10 and 15\u2009mg\/kg\/day) and METR (7.5 and 15\u2009mg\/kg\/day), both individually and in combination, over a 7\u2010day period. Subsequently, stool samples were collected and analyzed to assess the presence and viability of\n Giardia<\/jats:italic>\n cysts. The levels of secretory IgA (sIgA) in intestinal tissue, as well as the expression of tumor necrosis factor\u2010alpha (\n TNF-\u03b1<\/jats:italic>\n ), nuclear factor kappa B (\n NF-\u03baB<\/jats:italic>\n ), and interleukin\u20101 beta (\n IL-1\u03b2<\/jats:italic>\n ), were quantified using commercial ELISA kits and real\u2010time polymerase chain reaction (PCR), respectively.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n AGS exhibited a clear concentration\u2010dependent inhibitory effect on the viability of\n Giardia<\/jats:italic>\n trophozoites, with a calculated half\u2010maximal inhibitory concentration (IC\n 50<\/jats:sub>\n ) value of 30.24 \u00b1 2.43\u2009\n \u03bc<\/jats:italic>\n g\/mL. The administration of either METR or AGS (10 and 15\u2009mg\/kg) individually resulted in a partial reduction in both cyst quantity and viability. Notably, combined treatment with AGS and METR resulted in no detectable cysts in fecal samples collected 24\u2009h after the final treatment dose, within the detection limits of microscopy\u2010based analysis (\n p<\/jats:italic>\n < 0.001). Secretory IgA concentrations showed modest improvement following monotherapy but increased substantially after combination therapy (4.36\u2009ng\/mL,\n p<\/jats:italic>\n < 0.001). Correspondingly, elevated levels of pro\u2010inflammatory markers\n TNF-\u03b1<\/jats:italic>\n ,\n NF-\u03baB<\/jats:italic>\n , and\n IL-1\u03b2<\/jats:italic>\n observed in untreated mice (5.3\u2010, 4.29\u2010, and 5.16\u2010fold, respectively) were nearly restored to baseline values by the co\u2010administration regimen of AGS 15\u2009mg\/kg + METR\u20097.5\u2009mg\/kg (1.11\u2010, 0.86\u2010, and 0.91\u2010fold change,\n p<\/jats:italic>\n < 0.001). These findings indicate that AGS not only lacks hepatotoxicity but may also exert protective effects against infection\u2010associated hepatic dysfunction.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n AGS administration was associated with a reduced\n Giardia<\/jats:italic>\n cyst burden at the prespecified 24\u2010h post\u2010treatment endpoint, restoration of mucosal immune responses, attenuation of inflammatory signaling, and improved biochemical profiles in experimentally infected mice. These findings suggest that AGS may function as an immunomodulatory and anti\u2010inflammatory adjunct, potentially contributing to host\u2010mediated parasite load reduction and improved treatment outcomes when combined with METR. However, additional antiparasitic mechanisms and formal pharmacodynamic synergistic interactions were not demonstrated in this study and require further investigation through dedicated in vitro and mechanistic analyses.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1155\/japr\/1200923","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T13:06:09Z","timestamp":1786971969000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Astragaloside IV Combined With Metronidazole on Cyst Shedding and Mucosal Immune and Inflammatory Responses in a Murine Model of Giardiasis"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4194-393X","authenticated-orcid":false,"given":"Hossein","family":"Mahmoudvand","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7915-5503","authenticated-orcid":false,"given":"Amal Khudair","family":"Khalaf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5453-9741","authenticated-orcid":false,"given":"Sahar","family":"Mahmoudvand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4920-7857","authenticated-orcid":false,"given":"Ahmad","family":"Adineh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6521-3633","authenticated-orcid":false,"given":"Aram","family":"Oladi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6505-0719","authenticated-orcid":false,"given":"Javad Ghasemian","family":"Yadegari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"e_1_2_13_1_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i5369"},{"key":"e_1_2_13_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12664-012-0161-9"},{"key":"e_1_2_13_3_2","first-page":"3","article-title":"Giardia Lamblia Infection: Review of Current Diagnostic Strategies","volume":"12","author":"Hooshyar H.","year":"2019","journal-title":"Gastroenterology and Hepatology From Bed to Bench"},{"key":"e_1_2_13_4_2","doi-asserted-by":"crossref","DOI":"10.1007\/s11908-014-0396-y","article-title":"Treatment of Giardiasis: Current Status and Future Directions","volume":"16","author":"Watkins R. 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