{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T19:50:50Z","timestamp":1785268250564,"version":"3.55.0"},"reference-count":49,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T00:00:00Z","timestamp":1663545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research &amp; Innovation, Ministry of Education in Saudi Arabia","award":["442-17"],"award-info":[{"award-number":["442-17"]}]},{"name":"Taibah University","award":["442-17"],"award-info":[{"award-number":["442-17"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Alpha-mangostin (\u03b1-MN) is a xanthone obtained from Garcinia mangostana that has diverse anti-oxidative and anti-inflammatory potentials. However, its pharmacological activity against autoimmune hepatitis (AIH) has not been investigated before. Concanavalin A (Con A) was injected into mice to induce AIH and two doses of \u03b1-MN were tested for their protective effects against Con A-induced AIH. The results demonstrated the potent hepatoprotective activity of \u03b1-MN evidenced by a remarkable decrease of serum indices of the hepatic injury and amendment of the histological lesions. \u03b1-MN significantly attenuated the level and immuno-expression of myeloperoxidase (MPO) indicating a decrease in the neutrophil infiltration into the liver. Additionally, the recruitment of the CD4+ T cell was suppressed in the \u03b1-MN pre-treated animals. \u03b1-MN showed a potent ability to repress the Con A-induced oxidative stress evident by the reduced levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and protein carbonyl (PC), as well as the enhanced levels of antioxidants as the reduced glutathione (GSH), superoxide dismutase (SOD), and total antioxidant capacity (TAC). The ELISA, RT-PCR, and IHC analyses revealed that \u03b1-MN enhanced the sirtuin1\/nuclear factor erythroid 2 related factor-2 (SIRT1\/Nrf2) signaling and its downstream cascade genes concurrently with the inhibition of the nuclear factor kappa B (NF-\u03baB) and the inflammatory cytokines (tumor necrosis factor-alpha and interleukine-6) signaling. Taken together, these results inferred that the hepatoprotective activity of \u03b1-MN could prevent Con A-induced AIH through the modulation of the SIRT1\/Nrf2\/NF-\u03baB signaling. Hence, \u03b1-MN may be considered as a promising candidate for AIH therapy.<\/jats:p>","DOI":"10.3390\/plants11182441","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T04:28:55Z","timestamp":1663648135000},"page":"2441","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Alpha-Mangostin as a New Therapeutic Candidate for Concanavalin A-Induced Autoimmune Hepatitis: Impact on the SIRT1\/Nrf2 and NF-\u03baB Crosstalk"],"prefix":"10.3390","volume":"11","author":[{"given":"Ahmed M.","family":"Shehata","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Al-Madinah Al-Munawwarah 30078, Saudi Arabia"},{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossein M.","family":"Elbadawy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Al-Madinah Al-Munawwarah 30078, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6858-7560","authenticated-orcid":false,"given":"Sabrin R. M.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Preparatory Year Program, Department of Chemistry, Batterjee Medical College, Jeddah 21442, Saudi Arabia"},{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2971-6008","authenticated-orcid":false,"given":"Gamal A.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wael M.","family":"Elsaed","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisha A.","family":"Alhaddad","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Al-Madinah Al-Munawwarah 30078, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishat","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Al-Madinah Al-Munawwarah 30078, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hany","family":"Abo-Haded","sequence":"additional","affiliation":[{"name":"College of Medicine, Taibah University, Al-Madinah Al-Munawwarah 30078, Saudi Arabia"},{"name":"Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina S.","family":"El-Agamy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Al-Madinah Al-Munawwarah 30078, Saudi Arabia"},{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"108411","DOI":"10.1016\/j.intimp.2021.108411","article-title":"Pathogenesis of concanavalin A induced autoimmune hepatitis in mice","volume":"102","author":"Hao","year":"2022","journal-title":"Int. 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