{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T19:32:24Z","timestamp":1776799944005,"version":"3.51.2"},"reference-count":36,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T00:00:00Z","timestamp":1586908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The aim of this research was to examine the effect of the hydroalcoholic extracts from the peel (APE) and pulp (APP) of a traditional apple cultivar from central Italy (Mela Rosa dei Monti Sibillini) on CCl4-induced hepatotoxicity in rats. Phytoconstituents were determined by liquid chromatography\u2013mass spectrometry (LC-MS) analysis showing an abundance of proanthocyanidins and flavonol derivatives together with the presence of annurcoic acid in APE. Wistar rats received APE\/APP (30 mg\/kg oral administration) for three days before CCl4 injection (2 mL\/kg intraperitoneal once on the third day). Treatment with both APE and APP prior to CCl4 injection significantly decreased the serum levels of aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) compared to the CCl4 group. Besides, pretreatment with APE reversed the CCl4 effects on superoxide dismutase (SOD), myeloperoxidase (MPO), tumor necrosis factor-\u03b1 (TNF-\u03b1) and interleukin-1beta (IL-1\u03b2) levels in liver tissue in rats and reduced tissue damage as shown in hematoxylin and eosin staining. These results showed that this ancient Italian apple is worthy of use in nutraceuticals and dietary supplements to prevent and\/or protect against liver disorders.<\/jats:p>","DOI":"10.3390\/molecules25081816","type":"journal-article","created":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T09:19:50Z","timestamp":1586942390000},"page":"1816","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Hepatoprotective Effects of Standardized Extracts from an Ancient Italian Apple Variety (Mela Rosa dei Monti Sibillini) against Carbon Tetrachloride (CCl4)-Induced Hepatotoxicity in Rats"],"prefix":"10.3390","volume":"25","author":[{"given":"Hasan","family":"Yousefi-Manesh","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran 13145-784, Iran"},{"name":"Experimental medicine research center, Tehran University of Medical Sciences, Tehran 13145-784, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmad Reza","family":"Dehpour","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran 13145-784, Iran"},{"name":"Experimental medicine research center, Tehran University of Medical Sciences, Tehran 13145-784, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sedighe","family":"Ansari-Nasab","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran 13145-784, Iran"},{"name":"Experimental medicine research center, Tehran University of Medical Sciences, Tehran 13145-784, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6791-2202","authenticated-orcid":false,"given":"Sara","family":"Hemmati","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran 13145-784, Iran"},{"name":"Experimental medicine research center, Tehran University of Medical Sciences, Tehran 13145-784, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad Amin","family":"Sadeghi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran 13145-784, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reza Hashemi","family":"Shahraki","sequence":"additional","affiliation":[{"name":"Department of Medical Physics and Biomedical Engineering, School of Medicine, Tehran University of Medical Sciences, Tehran 13145-784, Iran"},{"name":"Preclinical Core Facility, Tehran University of Medical Sciences, Tehran 13145-784, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samira","family":"Shirooie","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6715847141, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seyed Mohammad","family":"Nabavi","sequence":"additional","affiliation":[{"name":"Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran 14359-16471, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joice G.","family":"Nkuimi Wandjou","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Camerino, 62032 Camerino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Sut","sequence":"additional","affiliation":[{"name":"Department of Agronomy, Food, Natural Resources, Animals and Environment, University of Padova, 35020 Legnaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5530-877X","authenticated-orcid":false,"given":"Giovanni","family":"Caprioli","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Camerino, 62032 Camerino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8264-6953","authenticated-orcid":false,"given":"Stefano","family":"Dall\u2019Acqua","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35121 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1375-4744","authenticated-orcid":false,"given":"Filippo","family":"Maggi","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Camerino, 62032 Camerino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1080\/09637486.2019.1580684","article-title":"Characterization of nutrients, polyphenols and volatile components of the ancient apple cultivar \u2018Mela Rosa Dei Monti Sibillini\u2019from Marche region, central Italy","volume":"70","author":"Sut","year":"2019","journal-title":"Int. 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