{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T04:36:22Z","timestamp":1784867782509,"version":"3.55.0"},"reference-count":58,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:00:00Z","timestamp":1756252800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Comprehensive Physiology"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Hepatic encephalopathy (HE) is a neuropsychiatric disorder associated with liver failure. Nesfatin\u20101 is a neuropeptide characterized by its antioxidant and anti\u2010inflammatory properties.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This study aimed to evaluate the neuroprotective and hepatoprotective effects of nesfatin\u20101 in a thioacetamide (TAA)\u2010induced rat model of acute HE. Additionally, the study aimed to examine the underlying mechanisms, particularly the role of the PI3K\/Akt\/Nrf2\/HO\u20101 signaling pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Male Sprague Dawley rats were divided into five groups: (1) untreated control, (2) nesfatin\u20101\u2010treated control, (3) thioacetamide\u2010induced hepatic encephalopathy (HE), (4) HE + nesfatin\u20101, and (5) HE + nesfatin\u20101\u2009+\u2009zinc protoporphyrin IX (ZnPP IX; HO\u20101 inhibitor). Assessments included behavioral analysis, serum liver function biomarkers, oxidative stress and inflammatory markers, brain water content, mRNA expression of HO\u20101 (Heme Oxygenase 1) and GFAP (Glial Fibrillary Acidic Protein), PI3K\/Akt\/Nrf2 protein levels, as well as histological and immunohistochemical evaluations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Nesfatin\u20101 significantly improved psychomotor activity, reduced serum ALT, AST, total bilirubin, and ammonia levels, and increased albumin. It also lowered brain MDA, TNF\u2010\u03b1, IL\u20106, and CRP levels, reduced brain water content, and upregulated the expression of HO\u20101 and GFAP. Furthermore, nesfatin\u20101 activated the PI3K\/Akt\/Nrf2 pathway and inhibited the expression of caspase\u20103 and NF\u2010\u03baB in liver and brain tissues. These protective effects were negated by HO\u20101 inhibition using ZnppIX. Histological analysis demonstrated the structural integrity of liver and brain tissues in rats treated with nesfatin\u20101.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Nesfatin\u20101 exerts potent hepatoprotective and neuroprotective effects in TAA\u2010induced hepatic encephalopathy via antioxidative, anti\u2010inflammatory, and antiapoptotic mechanisms involving the PI3K\/Akt\/Nrf2\/HO\u20101 pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cph4.70039","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T05:22:13Z","timestamp":1756358533000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Nesfatin\u20101 Exerts a Neuroprotective Effect in Thioacetamide\u2010Induced Acute Hepatic Encephalopathy by Activating the\n                    <scp>PI3K<\/scp>\n                    \/Akt\/Nrf2\/\n                    <scp>HO<\/scp>\n                    \u20101 Pathway"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0868-4737","authenticated-orcid":false,"given":"Heba","family":"Faheem","sequence":"first","affiliation":[{"name":"Physiology Department, Faculty of Medicine Tanta University  Tanta Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana","family":"Alawadhi","sequence":"additional","affiliation":[{"name":"Science Department College of Basic Education  Paaet Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8184-6459","authenticated-orcid":false,"given":"Eman H.","family":"Basha","sequence":"additional","affiliation":[{"name":"Physiology Department, Faculty of Medicine Tanta University  Tanta 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