{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T16:08:25Z","timestamp":1789834105488,"version":"4.0.1"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"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":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Alzheimer's disease (AD) is a neurodegenerative disorder associated with the loss of memory, accumulation of amyloid\u2010beta (A\u03b2) plaques, and inflammation of the nervous system. Scopolamine, an antagonist of muscarinic receptors, is commonly used to mimic the cognitive and behavioral deficits of AD in laboratory animals. In this study, we aimed to test the neuroprotective properties of hyperforin (HPF), a compound extracted from the St. John's wort plant (\n                    <jats:italic>Hypericum perforatum<\/jats:italic>\n                    ), in a scopolamine rat model of AD. Sprague\u2010Dawley rats were divided into four groups: control (saline), scopolamine (10\u2009mg\/kg, i.p.), scopolamine\u2009+\u2009hyperforin (10\u2009mg\/kg, p.o. for 7 days), and scopolamine\u2009+\u2009donepezil. Biochemical, and histopathological assessments were performed. Protein analysis related to inflammation, apoptosis, and the HMGB1\/RAGE signaling pathway was performed using Western blotting. IL\u20101\u03b1, levels were measured by ELISA. Nissl staining evaluated neuronal damage in the hippocampus. Hyperforin significantly suppressed the activation of the HMGB1\/RAGE signaling axis. Furthermore, hyperforin in this model also suppressed pyroptotic cell death and lowered IL\u20101\u03b1, IL\u20101\u03b2, and IL\u201018 levels. In addition, HPF reduced A\u03b2 formation by downregulating BACE1 and blocking the activity of inflammasomes composed of canonical and non\u2010canonical caspase\u20101\/11. HPF appears to be a potential therapeutic candidate for neurodegeneration associated with AD, given that hyperforin actively demonstrated neuroprotective effects in a scopolamine\u2010induced AD model, most likely through blocking the HMGB1\/RAGE signaling pathway, mitigating neuroinflammation and pyroptosis, and inhibiting A\u03b2 synthesis.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70753","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T20:45:14Z","timestamp":1773002714000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hyperforin Attenuates Scopolamine Induced Alzheimer's Pathology in Rat Model: Abrogation of Caspase\u20101\/11 Mediated Pyroptosis via Inhibition of HMGB1\u2010Mediated RAGE Pathway"],"prefix":"10.1002","volume":"40","author":[{"given":"Yan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Geriatrics Taizhou Hospital of Traditional Chinese Medicine Taizhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiumin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurology Shandong Provincial, Third Hospital JiNan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rami B.","family":"Kassab","sequence":"additional","affiliation":[{"name":"Zoology and Entomology Department, Faculty of Science Helwan University Cairo Egypt"},{"name":"Biology Department, Faculty of Science Al\u2010Baha University Al\u2010Baha Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed A.","family":"Elhefny","sequence":"additional","affiliation":[{"name":"Department of Cancer and Molecular Biology National Cancer Institute, Cairo University Cairo Egypt"},{"name":"Department of Medical Genetics, Faculty of Medicine Umm Al\u2010Qura University Alqunfudah Saudi 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