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Inflammatory bowel conditions can involve nearly all organ systems and induce pathological processes through increased oxidative stress, lipid peroxidation and disruption of the immune response. Patients with inflammatory bowel disease (IBD) are at high risk of having extra-intestinal manifestations, for example, in the hepatobiliary system. In 30% of patients with IBD, the blood values of liver enzymes, such as AST and ALT, are increased. Moreover, treatments for inflammatory bowel diseases may cause liver toxicity. Apple polyphenol extracts are widely acknowledged for their potential antioxidant effects, which help prevent damage from oxidative stress, reduce inflammation, provide protection to the liver, and enhance lipid metabolism. The aim of this study was to investigate whether the polyphenol apple extract from Malus domestica cv. 'Limoncella' (LAPE) may be an effective intervention for the treatment of IBD-induced hepatotoxicity. The LAPE was administrated in vivo by oral gavage (3–300 mg/kg) once a day for 3 consecutive days, starting 24 h after the induction of dinitro-benzenesulfonic acid (DNBS) colitis in mice. The results showed that LAPE significantly attenuated histological bowel injury, myeloperoxidase activity, tumor necrosis factor and interleukin (IL-1β) expressions. Furthermore, LAPE significantly improved the serum lipid peroxidation and liver injury in DNBS-induced colitis, as well as reduced the nuclear transcription factor-kappaB activation. In conclusion, these results suggest that LAPE, through its antioxidant and anti-inflammatory properties, could prevent liver damage induced by inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Additives can influence the processability and quality of three-dimensional (3D)-printed foods. Herein, the effects of apple polyphenols on the antioxidant activity and structure of 3D-printed processed cheese were investigated. The antioxidant activities of processed cheese samples with different contents of apple polyphenols (0%, 0.4%, 0.8%, 1.2%, or 1.6%) were evaluated using 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-di(4-tert-octylphenyl)-1-picrylhydrazyl (DPPH) assays. In addition, the rheological properties and structural characteristics of the processed cheeses were investigated using rheometry, Fourier transform infrared spectroscopy, and fluorescence spectroscopy. Then, the final printed products were analyzed for comparative molding effects and dimensional characteristics. it was found that apple polyphenols can significantly improve the antioxidant activity of processed cheese. When the amount of apple polyphenols added was 0.8%, the 3D shaping effect was optimal with a porosity rate of 4.1%. Apple polyphenols can be used as a good antioxidant additive, and the moderate addition of apple polyphenols can effectively improve the antioxidant and structural stability of 3D-printed processed cheese. [ABSTRACT FROM AUTHOR]

Plant secondary metabolites, known as phytochemicals, have recently gained much attention in light of the "circular economy", to reutilize waste products deriving from agriculture and food industry. Phytochemicals are known for their onco-preventive and chemoprotective effects, among several other beneficial properties. Apple phytochemicals have been extensively studied for their effectiveness in a wide range of diseases, cancer included. This review aims to provide a thorough overview of the main studies reported in the literature concerning apple phytochemicals, mostly polyphenols, in cancer prevention. Although there are many different mechanisms targeted by phytochemicals, the Nrf2 and NF-κB signaling pathways are the ones this review will be focused on, highlighting also the existing crosstalk between these two systems. [ABSTRACT FROM AUTHOR]

Plant-derived polyphenols exhibit beneficial effects on physiological and pathological processes, including cancer and neurodegenerative disorders, mainly because of their antioxidant activity. Apples are highly enriched in these compounds, mainly in their peel. The Tuscia Red (TR) apple variety exhibits the peculiar characteristic of depositing high quantities of polyphenols in the pulp, the edible part of the fruit. Since polyphenols, as any natural product, cannot be considered a panacea per se, in this paper, we propose to assess the biological effects of TR flesh extracts, in comparison with two commercial varieties, in a model system, the insect Drosophila melanogaster, largely recognized as a reliable system to test the in vivo effects of natural and synthetic compounds. We performed a comparative, qualitative and quantitative analysis of the polyphenol compositions of the three cultivars and found that TR flesh shows the highest content of polyphenols, and markedly, anthocyanins. Then, we focused on their effects on a panel of physiological, morphometrical, cellular and behavioral phenotypes in wild-type D. melanogaster. We found that all the apple polyphenol extracts showed dose-dependent effects on most of the phenotypes we considered. Remarkably, all the varieties induced a strong relenting of the cell division rate. [ABSTRACT FROM AUTHOR]

Polyphenols are antioxidant ingredients in apples and are related to human health because of their free radical scavenging activities. The polyphenolic profiles of old and new apple cultivars (n = 15) were analysed using high-performance liquid chromatography (HPLC) with diode array detection (DAD). The in vitro antioxidant capacity was determined by total phenolic content (TPC) assay, hydrophilic trolox equivalent antioxidant capacity (H-TEAC) assay and hydrophilic oxygen radical absorbance (H-ORAC) assay. Twenty polyphenolic compounds were identified in all investigated apples by HPLC analysis. Quercetin glycosides (203 ± 108 mg/100 g) were the main polyphenols in the peel and phenolic acids (10 ± 5 mg/100 g) in the flesh. The calculated relative contribution of single compounds indicated flavonols (peel) and vitamin C (flesh) as the major contributors to the antioxidant capacity, in all cultivars investigated. The polyphenolic content (HPLC data) of the flesh differed significantly between old (29 ± 7 mg/100 g) and new (13 ± 4 mg/100 g) cultivars, and the antioxidant capacity of old apple cultivars was up to 30% stronger compared to new ones. [ABSTRACT FROM AUTHOR]

Inhibitors of the Wingless-related Integration site (WNT)/β-catenin pathway have recently been under consideration as potential chemopreventive agents against Familial Adenomatous Polyposis (FAP). This autosomal-dominant syndrome is caused by germline mutations in the gene coding for the protein APC and leads to hyperactivation of the WNT/β-catenin signaling pathway, uncontrolled intestinal cell proliferation and formation of adenocarcinomas. The aim of the present work was to: (i) test, on in vitro cultures of cells carrying FAP mutations and on ex vivo biopsies of FAP patients, the WNT inhibitory activity of extracts from two common southern Italian apples, Malus pumila Miller cv. 'Annurca' and Malus domestica cv 'Limoncella'; (ii) identify the mechanisms underpinning their activities and; (iii) evaluate their potency upon gastrointestinal digestion. We here show that both Annurca and Limoncella apple extracts act as WNT inhibitors, mostly thanks to their polyphenolic contents. They inhibit the pathway in colon cells carrying FAP mutations with active dilutions falling in ranges close to consumer-relevant concentrations. Food-grade manufacturing of apple extracts increases their WNT inhibitory activity as result of the conversion of quercetin glycosides into the aglycone quercetin, a potent WNT inhibitor absent in the fresh fruit extract. However, in vitro simulated gastrointestinal digestion severely affected WNT inhibitory activity of apple extracts, as result of a loss of polyphenols. In conclusion, our results show that apple extracts inhibit the WNT pathway in colon cells carrying FAP mutations and represent a potential nutraceutical alternative for the treatment of this pathology. Enteric coating is advisable to preserve the activity of the extracts in the colon-rectal section of the digestive tract. [ABSTRACT FROM AUTHOR]

This clinical study was performed to evaluate the effects of continuous apple polyphenol (AP) administration on facial skin conditions and pigmentation induced by ultraviolet (UV) irradiation in healthy women participants. Participants (n = 65, age 20–39 years) were randomized to receive tablets containing AP (300 or 600 mg/day) or placebo in a double-blinded, placebo-controlled clinical trial. Continuous administration of AP for 12 weeks significantly prevented UV irradiation induced skin pigmentation (erythema value, melanin value, L value), although a dose-dependent relationship was not clearly observed. In contrast, no significant differences were detected between the groups with regard to water content and trans-epidermal water loss. Our study demonstrated that APs and their major active compounds, procyanidins, have several health benefits. Here, we report that continuous administration of AP for 12 weeks alleviated UV irradiation induced skin pigmentation, when compared with placebo, in healthy women. [ABSTRACT FROM AUTHOR]

Simple Summary: Excessive fat deposition (5–10%) in the liver could lead to liver damage and nonalcohol fatty liver disease (NAFLD). However, there is no satisfactory safe and effective measure of preventive and therapeutic treatments so far. Thus, the prevention of excessive fat deposition through diet modification might be a better strategy to protect humans from metabolic diseases. Due to the anatomical and physiological similarities between humans and pigs, the present study took the finishing pig as an animal model to investigate the effects of apple polyphenols on hepatic fat deposition and antioxidant capacity and their mechanisms. The present study indicated that apple polyphenols might be an effective dietary supplementation for decreasing the excessive fat deposition in liver tissue, improving lipid profiles and increasing the antioxidant capacity of finishing pigs. This study provides a better preventive strategy to protect humans from excessive fat deposition in the liver. Excessive fat deposition in the liver could lead to fatty liver and an increased risk of many metabolic diseases. Apple polyphenols (APPs), the major antioxidants in apples, possess wide-ranging beneficial biological functions. The present study aimed to investigate the effects of APPs on hepatic fat deposition and antioxidant capacity in finishing pigs, and their mechanisms. Results showed that APPs improved lipid profiles, increased antioxidant enzyme activities and reduced the fat deposition in the liver. In the liver, SOD1, CAT, GPX1, GST, NF-E2-related nuclear factor 2 (Nrf2), hormone sensitive lipase (HSL), carnitine palmitoyl transferase-1b (CPT1b), peroxisome proliferator-activated receptor α (PPARα), cholesterol 7α-hydroxylase (CYP7A1) and low-density lipoprotein receptor (LDL-R) mRNA levels were increased by APPs, while Kelch-like ECH-associated protein 1 (Keap1) mRNA level, C16:0 and C20:4n-6 proportions and Δ9-18 dehydrogenase activity were decreased. In conclusion, this study indicated that APPs might be an effective dietary supplementation for improving lipid profiles, increasing antioxidant capacities and decreasing fat deposition in the liver. [ABSTRACT FROM AUTHOR]

Reduction in cholesterol blood levels represents one of the therapeutic goals to achieve in order to reduce the occurrence of cardiovascular diseases. Commonly, this goal is attempted by promoting healthy lifestyle behaviors and low-fat diets. Recently, several nutraceuticals have been shown to possess cholesterol-lowering properties and are becoming common over the counter products. Among others, apple polyphenols efficiently lower total cholesterol levels in humans and impact overall lipid metabolism. Malus Pumila Miller cv Annurca is an apple native to Southern Italy presenting one of the highest content of procyanidin B2, a dimeric procyanidin. Tested in clinical trials, the oral consumption of an Annurca polyphenolic extract (AAE) exerted a cholesterol-lowering effect similar to the statins Atorvastatin and Simvastatin. Despite AAE activity, the analysis of the molecular mechanism behind its cholesterol-lowering effect is unclear. Using isotope labeling and high-resolution mass spectrometry approaches we here performed a metabolic profiling of in vitro cultured human hepatocytes treated with AAE to reveal its mechanism of action. The results show that AAE acts differently than statins. The extract reprograms hepatic cell metabolism and promotes mitochondrial respiration, lipolysis and fatty acid β-oxidation. Citrate and acetyl-CoA, both necessary for the production of cholesterol, are diverted to the Krebs Cycle by AAE, that, ultimately, lowers cholesterogenesis and fatty acid synthesis. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced alopecia (CIA) is a common side effect of conventional chemotherapy and represents a major problem in clinical oncology. Even months after the end of chemotherapy, many cancer patients complain of hair loss, a condition that is psychologically difficult to manage. CIA disturbs social and sexual interactions and causes anxiety and depression. Synthetic drugs protecting from CIA and endowed with hair growth stimulatory properties are prescribed with caution by oncologists. Hormones, growth factors, morphogens could unwontedly protect tumour cells or induce cancer cell proliferation and are thus considered incompatible with many chemotherapy regimens. Nutraceuticals, on the contrary, have been shown to be safe and effective treatment options for hair loss. We here show that polyphenols from Malus Pumila Miller cv Annurca are endowed with hair growth promoting activity and can be considered a safe alternative to avoid CIA. In vitro, Annurca Apple Polyphenolic Extract (AAE) protects murine Hair Follicles (HF) from taxanes induced dystrophy. Moreover, in virtue of its mechanism of action, AAE is herein proven to be compatible with chemotherapy regimens. AAE forces HFs to produce ATP using mitochondrial β-oxidation, reducing Pentose Phosphate Pathway (PPP) rate and nucleotides production. As consequence, DNA replication and mitosis are not stimulated, while a pool of free amino acids usually involved in catabolic reactions are spared for keratin production. Moreover, measuring the effect exerted on Poly Unsaturated Fatty Acid (PUFA) metabolism, we prove that AAE promotes hair-growth by increasing the intracellular levels of Prostaglandins F2α (PGF2α) and by hijacking PUFA catabolites toward β-oxidation. [ABSTRACT FROM AUTHOR]

Patterned hair loss (PHL) affects around 50% of the adult population worldwide. The negative impact that this condition exerts on people's life quality has boosted the appearance of over-the-counter products endowed with hair-promoting activity. Nutraceuticals enriched in polyphenols have been recently shown to promote hair growth and counteract PHL. Malus pumila Miller cv. Annurca is an apple native to Southern Italy presenting one of the highest contents of Procyanidin B2. We have recently shown that oral consumption of Annurca polyphenolic extracts (AAE) stimulates hair growth, hair number, hair weight and keratin content in healthy human subjects. Despite its activity, the analysis of the molecular mechanism behind its hair promoting effect is still partially unclear. In this work we performed an unprecedented metabolite analysis of hair follicles (HFs) in mice topically treated with AAE. The metabolomic profile, based on a high-resolution mass spectrometry approach, revealed that AAE re-programs murine HF metabolism. AAE acts by inhibiting several NADPH dependent reactions. Glutaminolysis, pentose phosphate pathway, glutathione, citrulline and nucleotide synthesis are all halted in vivo by the treatment of HFs with AAE. On the contrary, mitochondrial respiration, β-oxidation and keratin production are stimulated by the treatment with AAE. The metabolic shift induced by AAE spares amino acids from being oxidized, ultimately keeping them available for keratin biosynthesis. [ABSTRACT FROM AUTHOR]