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

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.

Prophylactic effect of myricetin and apigenin against lipopolysaccharide-induced acute liver injury

“…The histological analysis of liver was carried out according to standard method [24]. Liver tissues were collected from the sacrificed animals after the experimental period.…”

“…Finally, the tissues were embedded in paraffin at 62 °C and 5 μm thick sections were made by using microtome (HM 325, Thermo Scientific, USA) and attached to the glass slide. Thereafter, the sections were stained with haematoxylin and eosin [24]. The histology of liver was observed under a light microscope with × 40 magnification (Olympus-BX43, Japan).…”

Phytochemicals and Enzyme Inhibitory Capacities of the Methanolic Extracts from the Italian Apple Cultivar Mela Rosa dei Monti Sibillini

“…The consumption of the hydroalcoholic extracts of this cultivar has shown protective effects against renal ischemia/reperfusion injury and CCl 4 -induced hepatotoxicity in rats [18,19].…”

Therapeutic Effects of Hydroalcoholic Extracts from the Ancient Apple Mela Rosa dei Monti Sibillini in Transient Global Ischemia in Rats

“…In this regard, the application of natural products appears to be a good approach to decrease the mortality of strokes. Among fruits and vegetables regarded as sources of phytonutrients capable of preventing damage from oxidative stress and inflammation, the apple is considered one of the most important from a nutraceutical standpoint [16].…”

“…Our group has recently focused on the Mela Rosa dei Monti Sibillini, an ancient apple variety cultivated by Romans in the foothills of the Sibillini Mountains, central Italy, between 400 and 900 m of altitude, and recognizable by its small size, its irregular shape, its shades ranging from pink to purplish red, its intense and aromatic aroma and its sour and sugary flavor [19]. This fruit has been revealed to be rich in polyphenols such as flavan-3-ols/procyanidins, dihydrochalcones, flavonols, and hydroxycinnamic acids, as well as triterpene acids including annurcoic and ursolic acids, being valuable as source of nutraceuticals useful to manage conditions related to inflammation and oxidative stress [16]. As a matter of fact, in several studies apple peel extract (APE) and apple pulp extract (APP) have shown anti-inflammatory and anti-oxidative stress effects in animal models of renal ischemia/reperfusion injury, carbon tetrachloride (CCl4)-induced hepatotoxicity, diabetic pancreas model and colitis via down regulation of NF-kB, pro-inflammatory cytokines, increasing the antioxidant enzyme activity including superoxide dismutase (SOD), catalase (CAT) and reducing myeloperoxidase (MPO) activity [1,[17][18][19].…”