Hepatoprotective Effects of Standardized Extracts from an Ancient Italian Apple Variety (Mela Rosa dei Monti Sibillini) against Carbon Tetrachloride (CCl4)-Induced Hepatotoxicity in Rats.

Hasan Yousefi-Manesh,Sedighe Ansari-Nasab,Stefania Sut,Seyed Mohammad Nabavi,Joice G Nkuimi Wandjou,Reza Hashemi Shahraki,Ahmad Reza Dehpour,Giovanni Caprioli,Sara Hemmati,Mohammad Amin Sadeghi,Stefano Dall’Acqua,Samira Shirooie,Filippo Maggi

doi:10.3390/molecules25081816

Abstract

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–mass 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-α (TNF-α) and interleukin-1beta (IL-1β) 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.

Highlights

The Mela Rosa dei Monti Sibillini is a small ancient apple, cultivated in the pre-Apennine zone of the Sibillini Mountains in central Italy, at an altitude between 400 and 900 m a.s.l
Detailed chemical analysis of apple peel (APE) and APP was the subject of a previous work [1] and revealed a complex pattern of phytoconstituents comprising phloretin glycosides, hydroxycinnamic acid derivatives, quercetin derivatives and procyanidins of the B group as the most abundant phytochemicals
To assess a possible role of these constituents in this work we obtained a fingerprint of the extract and we used the overall content of phenolics and triterpene acids measured in the samples used for the in vivo test

Summary

Introduction

The Mela Rosa dei Monti Sibillini is a small ancient apple, cultivated in the pre-Apennine zone of the Sibillini Mountains in central Italy, at an altitude between 400 and 900 m a.s.l. Apple (Malus spp.), one of the most widely obtainable fruits, contains phenolic compounds belonging to the following classes: flavan-3-ols/procyanidins (catechin, epicatechin and procyanidins A, B), flavonols (quercetin derivatives), dihydrochalcones (phloretin and its glycosylated form phloridzin) and hydroxycinnamic acids (chlorogenic acid) [1,3]. It is known as a good source of triterpene acids, especially in the peel, such as ursolic, annurcoic and oleanolic acids [1,3,4]

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