Evidence of an additional centre of apple domestication in Iran, with contributions from the Caucasian crab apple Malus orientalis Uglitzk. to the cultivated apple gene pool.

Divergence processes in crop-wild fruit tree complexes in pivotal regions for plant domestication such as the Caucasus and Iran remain little studied. We investigated anthropogenic and natural divergence processes in apples in these regions using 26 microsatellite markers amplified in 550 wild and cultivated samples. We found two genetically distinct cultivated populations in Iran that are differentiated from Malus domestica, the standard cultivated apple worldwide. Coalescent-based inferences showed that these two cultivated populations originated from specific domestication events of Malus orientalis in Iran. We found evidence of substantial wild-crop and crop-crop gene flow in the Caucasus and Iran, as has been described in apple in Europe. In addition, we identified seven genetically differentiated populations of wild apple (M. orientalis), not introgressed by the cultivated apple. Niche modelling combined with genetic diversity estimates indicated that these wild populations likely resulted from range changes during past glaciations. This study identifies Iran as a key region in the domestication of apple and M. orientalis as an additional contributor to the cultivated apple gene pool. Domestication of the apple tree therefore involved multiple origins of domestication in different geographic locations and substantial crop-wild hybridization, as found in other fruit trees. This study also highlights the impact of climate change on the natural divergence of a wild fruit tree and provides a starting point for apple conservation and breeding programmes in the Caucasus and Iran.

Differential Radiomodulating Action of Olea europaea L. cv. Caiazzana Leaf Extract on Human Normal and Cancer Cells: A Joint Chemical and Radiobiological Approach.

The identification of a natural compound with selectively differential radiomodulating activity would arguably represent a valuable asset in the striving quest for widening the therapeutic window in cancer radiotherapy (RT). To this end, we fully characterized the chemical profile of olive tree leaf polyphenols from the Caiazzana cultivar (OLC), autochthonous to the Campania region (Italy), by ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HR-MS). Oleacein was the most abundant molecule in the OLC. Two normal and two cancer cells lines were X-ray-irradiated following 24-h treatment with the same concentration of the obtained crude extract and were assessed for their radioresponse in terms of micronucleus (MN) induction and, for one of the normal cell lines, of premature senescence (PS). Irradiation of pre-treated normal cells in the presence of the OLC reduced the frequency of radiation-induced MN and the onset of PS. Conversely, the genotoxic action of ionising radiation was exacerbated in cancer cells under the same experimental conditions. To our knowledge, this is the first report on the dual action of a polyphenol-rich olive leaf extract on radiation-induced damage. If further confirmed, these findings may be pre-clinically relevant and point to a substance that may potentially counteract cancer radioresistance while reducing RT-associated normal tissue toxicity.

Could Polyphenols Really Be a Good Radioprotective Strategy?

Currently, radiotherapy is one of the most effective strategies to treat cancer. However, deleterious toxicity against normal cells indicate for the need to selectively protect them. Reactive oxygen and nitrogen species reinforce ionizing radiation cytotoxicity, and compounds able to scavenge these species or enhance antioxidant enzymes (e.g., superoxide dismutase, catalase, and glutathione peroxidase) should be properly investigated. Antioxidant plant-derived compounds, such as phenols and polyphenols, could represent a valuable alternative to synthetic compounds to be used as radio-protective agents. In fact, their dose-dependent antioxidant/pro-oxidant efficacy could provide a high degree of protection to normal tissues, with little or no protection to tumor cells. The present review provides an update of the current scientific knowledge of polyphenols in pure forms or in plant extracts with good evidence concerning their possible radiomodulating action. Indeed, with few exceptions, to date, the fragmentary data available mostly derive from in vitro studies, which do not find comfort in preclinical and/or clinical studies. On the contrary, when preclinical studies are reported, especially regarding the bioactivity of a plant extract, its chemical composition is not taken into account, avoiding any standardization and compromising data reproducibility.

Valle Agricola Chickpeas: Nutritional Profile and Metabolomics Traits of a Typical Landrace Legume from Southern Italy.

Chickpea (Cicer arietinum L.) from Valle Agricola is a legume cultivated in Southern Italy whose intake is strictly linked to rural traditions. In order to get new biochemical insight on this landrace and to promote its consumption and marketing, nutritional values (moisture content, total proteins, lipids, total and free amino acids) and metabolic traits are deeply investigated. Valle Agricola chickpea is nutritionally rich in proteins (19.70 g/100 g) and essential amino acids (7.12 g/100 g; ~40% of total). Carbohydrates, whose identity was unraveled by means of UHPLC-HR MS/MS analysis, were almost 60% of chemicals. In particular, a di-galactosylglycerol, a pinitol digalactoside, and a galactosylciceritol were found as constitutive, together with different raffinose-series oligosaccharides. Although lipids were the less constitutive compounds, glycerophospholipids were identified, while among free fatty acids linoleic acid (C18:2) was the most abundant, followed by oleic (C18:1) and palmitic (C16:0) acids. Isoflavones and hydroxybenzoic acid derivatives were also detected. Valle Agricola chickpeas showed very good levels of several mineral nutrients, especially magnesium (164 mg/100 g), potassium (748 mg/100 g), calcium (200 mg/100 g), zinc (4.20 mg/100 g) and manganese (0.45 mg/100 g). The boiling process favorably decreases anti-trypsin and anti-chymotrypsin activities, depleting this precious seed of its intrinsic antinutritional factors.

Anthocyanin derivatives as potent inhibitors of SARS-CoV-2 main protease: An in-silico perspective of therapeutic targets against COVID-19 pandemic.

A new pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide and become pandemic with thousands new deaths and infected cases globally. To treat the patients with coronavirus disease (COVID-19), currently no effective drug or vaccine is available. This necessity motivated us to explore potential lead compounds based natural products targeting main protease (Mpro) enzyme of SARS-CoV-2. The Mpro enzyme plays a key role in mediating viral replication and transcription and thus being considered as an attractive drug target. Herein, comprehensive computational investigations were performed to identify new lead compounds against main protease enzyme. In this study, the candidate anthocyanin-derived compounds from PubChem database were filtered considering antiviral characteristics of anthocyanins. The structure-based pharmacophore modeling was developed based on the co-crystallized structure of the enzyme with its biological active inhibitor. The generated hypotheses were applied for virtual screening-based PHASE Screen Score. Docking based virtual screening work flow was used to generate hit compounds using HTVS, SP and XP based Glide Gscore. The obtained hit compounds were filtered using ADMET pharmacological and physicochemical properties screening. Molecular dynamics simulations were performed to explore the binding affinities of the considered compounds. Our study identified six best anthocyanin-derived natural compounds which could be used as promising lead compounds against main protease SARS-CoV-2 virus.

Polyphenols vs. Coronaviruses: How Far Has Research Moved Forward?

The epidemic, caused by SARS-CoV-2 at the beginning of 2020, led us to a serious change in our lifestyle that for about three months has confined us to our homes, far from our laboratory routine. In this period, the belief that the work of a researcher should never stop has been the driving force in writing the present paper. It aims at reviewing the recent scientific knowledge about in vitro experimental data that focused on the antiviral role of phenols and polyphenols against different species of coronaviruses (CoVs), pointing up the viral targets potentially involved. In the current literature scenario, the papain-like and the 3-chymotrypsin-like proteases seem to be the most deeply investigated and a number of isolated natural (poly)phenols has been screened for their efficacy.

Transgenic apple plants overexpressing the chalcone 3-hydroxylase gene of Cosmos sulphureus show increased levels of 3-hydroxyphloridzin and reduced susceptibility to apple scab and fire blight.

MAIN CONCLUSION: Overexpression of chalcone-3-hydroxylase provokes increased accumulation of 3-hydroxyphloridzin in Malus . Decreased flavonoid concentrations but unchanged flavonoid class composition were observed. The increased 3-hydroxyphlorizin contents correlate well with reduced susceptibility to fire blight and scab. The involvement of dihydrochalcones in the apple defence mechanism against pathogens is discussed but unknown biosynthetic steps in their formation hamper studies on their physiological relevance. The formation of 3-hydroxyphloretin is one of the gaps in the pathway. Polyphenol oxidases and cytochrome P450 dependent enzymes could be involved. Hydroxylation of phloretin in position 3 has high similarity to the B-ring hydroxylation of flavonoids catalysed by the well-known flavonoid 3'-hydroxylase (F3'H). Using recombinant F3'H and chalcone 3-hydroxylase (CH3H) from Cosmos sulphureus we show that F3'H and CH3H accept phloretin to some extent but higher conversion rates are obtained with CH3H. To test whether CH3H catalyzes the hydroxylation of dihydrochalcones in planta and if this could be of physiological relevance, we created transgenic apple trees harbouring CH3H from C. sulphureus. The three transgenic lines obtained showed lower polyphenol concentrations but no shift between the main polyphenol classes dihydrochalcones, flavonols, hydroxycinnamic acids and flavan 3-ols. Increase of 3-hydroxyphloridzin within the dihydrochalcones and of epicatechin/catechin within soluble flavan 3-ols were observed. Decreased activity of dihydroflavonol 4-reductase and chalcone synthase/chalcone isomerase could partially explain the lower polyphenol concentrations. In comparison to the parent line, the transgenic CH3H-lines showed a lower disease susceptibility to fire blight and apple scab that correlated with the increased 3-hydroxyphlorizin contents.

Red-fleshed Apples: Old Autochthonous Fruits as a Novel Source of Anthocyanin Antioxidants.

In order to promote breeding programs and a full reintroduction into production of two local red-fleshed apple varieties grown in Bekran and Bastam (Iran), the evaluation of their antioxidant properties was of interest. LC-MS(n) based metabolic fingerprinting analyses were applied to investigate the anthocyanin content of both peel and flesh components of the fruits. Cyanidin-3-O-hexoside isomers were present in both 'Bekran' and 'Bastam' apples, whereas 'Bekran' apple was a valuable source of anthocyanin rutinose derivatives. Employing DPPH(•), ABTS(•+), and ORAC methods, the antiradical efficacy was evaluated. The ability of the investigated fruit components to scavenge OH(•), and O(2) (•-) reactive species was also assessed. ID(50) values highlighted the massive antioxidant response of 'Bekran' peel component, able to counteract by 50 % OH(•), and O(2) (•-) at 130.3 and 91.6 µg/mL, respectively. The cytoprotective screening towards HeLa, HepG2, A549, SH-5YSY, and SK-N-BE(2)-C cell lines evidenced that the investigated Iranian red-fleshed apple fruits were able to exert a significant antioxidant response in hydrogen peroxide oxidized cell systems. Data collected suggested that the revaluation of 'Bekran' and 'Bastam' apple cultivars could represent a precious source of antioxidant compounds whose dietary intake could improve the human well-being reducing risks of free radical related chronic and degenerative diseases.