{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T05:04:39Z","timestamp":1789362279747,"version":"build-2803163510"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Methamphetamine (METH) abuse is linked to significant hepatic injury, driven by oxidative stress, inflammatory pathway activation, autophagic dysregulation, and apoptosis induction. This study explored the hepatoprotective and anti\u2010inflammatory potential of the brown seaweed\n                      <jats:italic>Hormophysa cuneiformis<\/jats:italic>\n                      extract against METH\u2010induced liver damage in adult male Wistar rats.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Extracts prepared using methanol, ethanol, hexane, and water were screened for antioxidant activity. The methanolic extract, selected for further investigation, was characterized by phytochemical analysis and GC\u2013MS profiling. Molecular docking was performed to evaluate the interactions of the identified bioactive compounds with TNF\u2010\u03b1 and LC3B\u2010II. The cytotoxicity and selectivity of the methanolic extract were assessed using HepG\u20102 hepatocellular carcinoma and WI\u201038 normal cells. Its hepatoprotective effects were further evaluated in vivo in METH\u2010treated adult male Wistar rats using biochemical, Western blot, immunohistochemical, and histopathological analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The methanolic extract showed the greatest antioxidant activity, achieving 57.16% \u00b1 1.96% DPPH radical scavenging and 54.71% \u00b1 0.84% ferric\u2010reducing antioxidant power. Although these values were lower than those of ascorbic acid (97.23 \u00b1 0.48%), the methanolic extract exhibited higher antioxidant potential than the other extracts. Secondary metabolites, including alkaloids, saponins, tannins, and total phenolic compounds, were detected in notable amounts. GC\u2010MS analysis identified oleic acid, palmitic acid, linoleic acid, and arachidonic acid as the major constituents. The extract exhibited dose-dependent cytotoxicity against HepG\u20132 cells, with an IC50 of 77.14 \u00b1 1.63 \u00b5g mL\n                      <jats:sup>\u22121<\/jats:sup>\n                      , while showing lower toxicity toward WI-38 cells (CC50 = 141.99 \u00b1 3.54 \u00b5g mL\n                      <jats:sup>\u22121<\/jats:sup>\n                      ), indicating selective antiproliferative activity and a favorable safety margin. In vivo, METH administration significantly elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels. Oral co-treatment with the\n                      <jats:italic>H. cuneiformis<\/jats:italic>\n                      methanolic extract (15 mg kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) significantly attenuated METH-induced hepatocellular injury, lowering serum ALT from 89.33 to 54.33 U L\n                      <jats:sup>\u22121<\/jats:sup>\n                      , AST from 294.33 to 57.33 U L\n                      <jats:sup>\u22121<\/jats:sup>\n                      , and ALP from 264.67 to 189.00 U L\n                      <jats:sup>\u22121<\/jats:sup>\n                      . Western blot analysis showed that METH markedly increased LC3B-II and Beclin-1 expression, whereas co-administration of the extract significantly reduced both proteins. Immunohistochemical analysis also demonstrated increased caspase-3- and NF-\u03baB-positive cells in the METH-treated group, which were significantly reduced following H. cuneiformis treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Collectively, these findings suggest that\n                      <jats:italic>H. cuneiformis<\/jats:italic>\n                      exerts hepatoprotective effects against METH-induced liver injury through antioxidant, anti-inflammatory, anti-apoptotic, and autophagy-modulating mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1913493","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T04:38:40Z","timestamp":1789360720000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Hormophysa cuneiformis protects against methamphetamine-induced hepatotoxicity via antioxidant, anti-inflammatory, and autophagy-regulatory mechanisms: histological and biochemical studies"],"prefix":"10.3389","volume":"17","author":[{"given":"Mayada","family":"Elhusseiny","sequence":"first","affiliation":[{"name":"Histology and Cell Biology Department, Faculty of Medicine, Tanta University","place":["Tanta, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabab S.","family":"El-Kelany","sequence":"additional","affiliation":[{"name":"Forensic Medicine and Clinical Toxicology at the Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Tanta University","place":["Tanta, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rania A.","family":"El-Shenody","sequence":"additional","affiliation":[{"name":"Botany and Microbiology Department, Faculty of Science, Tanta University","place":["Tanta, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed S.","family":"El-Hashash","sequence":"additional","affiliation":[{"name":"Botany and Microbiology Department, Faculty of Science, Tanta University","place":["Tanta, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mostafa E.","family":"Elshobary","sequence":"additional","affiliation":[{"name":"Botany and Microbiology Department, Faculty of Science, Tanta University","place":["Tanta, Egypt"]},{"name":"Aquaculture Research, AWI-Helmholtz Centre for Polar and Marine Research","place":["Bremerhaven, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samar Sami","family":"Alkafaas","sequence":"additional","affiliation":[{"name":"Molecular Cell Biology Unit, Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University","place":["Tanta, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"135","DOI":"10.62877\/18-ijcbs-24-26-20-18","article-title":"Antioxidant activity and tyrosinase of brown seaweed extract using ultrasonic and magnetic stirrer extraction methods","volume":"26","author":"Abubakar","year":"2024","journal-title":"Int. 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