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Abstract: New naphthalimidopropyl, bisphthalimidopropyl and bisnaphthalimidopropyl (BNIP) derivatives were synthesised and characterised. Their interactions with Calf Thymus DNA were studied by UV spectrophotometric analysis and a competitive Ethidium bromide displacement assay. Cytotoxicity was determined by MTT assay in a breast cell system (MDA-MB-231 and MCF-10A cells). All BNIPs exhibited strong DNA-binding properties and cytotoxic activity with IC50 values in the range of 0.83–12.68 μM (24 and 48 h treatment). In addition, the uptake of BNIP derivatives within cancer cells was not via utilisation of the MGBG polyamine transporter. Put together the results confirm that the presence of the bisnaphthalimidopropyl and alkyl linker functionality are crucial for exerting DNA-binding and cytotoxic properties, hence demonstrating promise in their further development as potential anti cancer agents. [Copyright &y& Elsevier]

Rapeseed pomace (RSP) is a waste product obtained after edible oil production from Brassica napus . Analysis of ubiquitous secondary metabolites in RSP samples (two breeds, harvested in 2012/2014 respectively from North East of Scotland) and their ethanol/water (95:5) Soxhlet extracts were carried out. Soxhlet extraction of the RSP (petroleum ether followed by 95% ethanol) gave a solid extract. LC-MS/MS data of the extracts revealed several secondary metabolites, with Sinapic acid being the most abundant. Strong antioxidant activities of the Soxhlet extracts were confirmed from the results obtained in the FRAP, DPPH and ORAC assays. Furthermore, for the very first time, RSP extracts (13.9 µg/ml) provided complete DNA protection, from oxidative stress induced by AAPH (3.5 mM). Therefore the strong antioxidant and DNA protecting properties demonstrated by the RSP extracts in this study warrants further investigation for their revalorisation and potential use as reliable source of antioxidants in different food applications. [ABSTRACT FROM AUTHOR]

Obesity is a major risk factor for several diseases, including metabolic syndrome (MetS), non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D). The use of natural products, such as astaxanthin (ASX), a potent antioxidant compound produced by the freshwater green microalga Haematococcus pluvialis, has gained particular interest to reduce oxidative stress and inflammation, and to improve redox status, often associated with obesity. A systematic review and meta-analysis was performed to comprehensively examine the effects of ASX in animal models of diet induced obesity-associated diseases in order to inform the design of future human clinical studies for ASX use as supplement or nutraceutical. Cinahl, Cochraine, MEDLINE, Scopus and Web of Science were searched for English-language manuscripts published between January 2000 and April 2020 using the following key words: astaxanthin, obesity, non-alcoholic fatty liver disease, diabetes mellitus type 2, NAFLD and metabolic. Seventeen eligible articles, corresponding to 21 animal studies, were included in the final quantitative analysis. ASX, at different concentrations and administered for different length of time, induced a significant reduction in adipose tissue weight (P = 0.05) and systolic blood pressure (P < 0.0001) in control animals. In animal models of T2D, ASX significantly reduced serum glucose levels (P = 0.04); whereas it improved several disease biomarkers in the blood (e.g. cholesterol, triglycerides, ALT and AST, P < 0.10), and reduced liver (P = 0.0002) and body weight (P = 0.11), in animal models of NAFLD. Supplementation of ASX in the diet has positive effects on symptoms associated with obesity related diseases in animals, by having lipid-lowering, hypo-insulin and hypoglycaemic capacity, protecting organs from oxidative stress and mitigating the immune system, as suggested in this review. [Display omitted] • First meta-analysis on ASX effects in animal models of MetS, T2D and NAFLD. • ASX dietary supplementation positively affects symptoms in obesity related diseases. • ASX has lipid-lowering, hypo-insulin and hypoglycaemic capacity. • ASX protects organs from oxidative stress and modulates immune system. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PaCa) is one of the deadliest cancers known and its incidence is increasing in the developed countries. Because of the lack of biomarkers that allow early detection and the tendency of the disease to be asymptomatic, the diagnosis comes often too late for effective surgical or chemotherapy intervention. Lifestyle factors, that may cause common genetic modifications occurring in the disease, interfere with pancreatic physiology or function, and play a role in PaCa development, have been of concern recently, since a strategy to prevent this severe cancer is needed. This review identifies the latest evidences related to increased risk of developing PaCa due to dietary habits such as high alcohol, fructose and red or processed meat intake, and pathological conditions such as diabetes, obesity and infections in addition to stress and smoking behaviour. It aims to highlight the importance of intervening on modifiable risk factors: the action on these factors could prevent a considerable number of new cases of PaCa. • Smoking, high alcohol and red meat intake increase pancreatic cancer (PaCa) risk. • Obesity and diabetes stimulate insulin production and predispose to onset of PaCa. • Lifestyle and behaviour are linked with PaCa by plausible biological processes. • Inflammation a potential common mechanism to lifestyle environment, diseases and PaCa. [ABSTRACT FROM AUTHOR]

For a number of years there has been intense interest in phytochemicals due to their potential health benefits. One readily available and rich source of phytochemicals is Rapeseed pomace (RSP), a waste product obtained after edible oil production from Brassica napus . In this work, we analysed the ubiquitous secondary metabolites in RSP (harvest 2014, North East of Scotland) after soxhhlet ethanol/water (95:5) extraction. LC-MS/MS data of the extract revealed several secondary metabolites, with sinapic acid being the most abundant. The presence of a high level of phenolics in the extract was confirmed with the folin ciocalteu assay. Strong antioxidant activities of the extract was determined by using common antioxidant assays (FRAP, DPPH and ORAC). In addition, the extract (13.9 μg/mL) provided complete pBR322 plasmid DNA protection, from oxidative stress induced by AAPH (3.5 mM). Interestingly, in vitro analysis showed that the RSP extract exhibited acetylcholinesterase inhibition activity in a time and concentration dependant manner. Furthermore, cellular studies showed that incubation of neuroblastoma cells (SH Sy-5Y) with RSP extract protected cell metabolism from reactive oxygen species produced by H 2 O 2 (1 mM). We are currently undertaking in vivo studies using the model organism C. elegans . Preliminary results showed that RSP extract is non-toxic (up to 5 mg/mL) and has neuroprotective properties in C. elegans models of neurodegenerative diseases (work in progress). The positive properties associated with the RSP extract in this study warrants further investigation for the revalorisation of rapeseed pomace in the health/food industry. [ABSTRACT FROM AUTHOR]

Bisnaphthalimidopropyl diaminodicyclohexylmethane (BNIPDaCHM) bisintercalates to DNA and is a potential anti-cancer therapeutic. In an attempt to elucidate the mechanism(s) underlying the potential of BNIPDaCHM; earlier work was extended to investigate its effect on DNA damage and repair as well as cell cycle modulation, in a triple negative breast cancer (TNBC) cell line in vitro . BNIPDaCHM significantly decreased cell viability in a concentration (≥5 μM) and time (≥24 h) dependent manner. The mechanism of this growth inhibition involved alterations to cell cycle progression, an increase in the sub-G1 population and changes to plasma membrane integrity/permeability observed by flow cytometry and fluorescence microscopy with acridine orange/ethidium bromide staining. Using single cell gel electrophoresis (Comet assay) and fluorescence microscopy to detect γ-H2AX-foci expression; it was found that after 4 h, ≥ 0.1 μM BNIPDaCHM treatment-induced significant DNA double strand breaks (DSBs). Moreover, exposure to a non-genotoxic concentration of BNIPDaCHM induced a significant decrease in the repair of oxidative DNA strand breaks induced by hydrogen peroxide. Also, BNIPDaCHM-treatment induced a significant time dependent increase in p21 Waf/Cip1 mRNA expression but, did not alter p53 mRNA expression. In conclusion, BNIPDaCHM treatment in MDA-MB-231 cells was associated with a significant induction of DNA DSBs and inhibition of DNA repair at non-genotoxic concentrations via p53-independent expression of p21 Waf1/Cip1 . The latter may be a consequence of novel interactions between BNIPDaCHM and MDA-MB-231 cells which adds to the spectrum of therapeutically relevant activities that may be exploited in the future design and development of naphthalimide-based therapeutics. [ABSTRACT FROM AUTHOR]

Lipids excess from an uterine environment can increase free radicals production of and thus induce oxidative status imbalance, a key factor for progression of non-alcoholic fatty liver disease (NAFLD) in offspring. Food antioxidant components in maternal diet may play an important role in preventing offspring metabolic disorders. The objective of the study was to evaluate the effects of açaí pulp supplementation on maternal high-fat diet, by assessing activity and expression of antioxidant enzymes and biomarkers of oxidative stress in the liver. Female Fisher rats were divided into four groups and fed a control diet (C), a high-fat diet (HF), a control diet supplemented with açaí (CA) and a high-fat diet supplemented with açaí (HFA) before mating, during gestation and lactation. The effects of açaí supplementation on oxidative stress biomarkers and antioxidant enzymes expression were evaluated in dams and male offspring after weaning. HFA diet increased body weight in dams, however reduced absolute and relative liver weight. There was a reduction in liver biomarkers of oxidative stress, malondialdehyde and carbonyl protein, as well as in catalase, glutathione peroxidase and superoxide dismutase activity. In offspring, HFA diet reduced liver weight and increased Gpx1, Gpx4 and Sod1 mRNA expression. These results suggest that açaí is able to restore redox status, preventing oxidative damage in dams by a direct mechanism and to promote beneficial effects on expression of antioxidant defences related genes in offspring. In this work, we demonstrated for the first time that açaí pulp supplementation to maternal high-fat diet may protect offspring from oxidative stress. These results showed a reduction in biomarkers of oxidative stress and antioxidants enzymes in dams. There was an increase in Gpx1, Gpx4 and Sod1 mRNA expression in offspring. Açaí pulp supplementation to maternal diet induced protection through modulation of oxidative stress by a direct mechanism in dams and may promote beneficial effects on antioxidant defences in offspring. [Display omitted] • Supplementation of açaí pulp to a maternal high fat diet prevents oxidative damage in dams and improves offspring antioxidant defences. • Supplementation of high fat diet with açaí reduces liver oxidative stress biomarkers. • Açaí supplementation to high fat diet reduces liver CAT, GPX, SOD activity in dams. • Açaí supplementation to maternal high fat diet reduces liver weight in offspring. • Maternal açaí supplemented high fat diet increases offspring liver Gpx1 , Gpx4, Sod1. [ABSTRACT FROM AUTHOR]

This special issue of Biochemical Pharmacology contains proceedings of a joint conference sponsored by the Natural Products Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the International Conference on the Mechanism of Action of Nutraceuticals (ICMAN), an organization dedicated to defining actions and clinical benefits of pharmaceuticals and nutraceuticals. Entitled “From Nutraceuticals to Pharmaceuticals: Common Challenges and Approaches” , the conference was held in Aberdeen UK in September 2017. The aim of this gathering was to identify the challenges that must be overcome to identify and characterize novel therapeutics from natural products. Contained in this issue are reviews prepared by conference participants as well as abstracts describing oral and poster presentations. [ABSTRACT FROM AUTHOR]

Natural products have recently been exploited as alternative sources of cancer chemo-preventative agents. Induction of cell cycle arrest and apoptosis, and prevention of carcinogenesis and cancer progression are some of the mechanisms studied in cell systems and animal models. By-products from rapeseed oil extraction processes, however, have not been studied before: this study aims to assess the potential anti-cancer properties of extracts from rapeseed pomace (RSP), the by-product of cold pressed rapeseed oil production. RSP was extracted using accelerated solvent extraction (ASE) with different ethanol (EtOH) to water (dH 2 O) ratios: 50:50 EtOH:dH 2 O RSP extract showed significantly higher concentrations in Gallic Acid Equivalent (Folin Ciocalteu assay) compared to controls, and a significant increase in free radical scavenging properties (DPPH assay) was observed for 50:50 and 20:80 EtOH:dH 2 O RSP extracts. Moreover, extracts’ anticancer properties were assessed in a breast cancer cell line, MDA-MB-231. The three RSP extracts did not show cell cytotoxicity at concentrations ⩽1 mg/ml; however, at 2.5 mg/ml, 50:50 EtOH:dH 2 O RSP extract significantly decreased cell viability by 72% and, at 5 mg/ml, all extracts were cytotoxic. Cell treatment with 50:50 EtOH:dH 2 O RSP extract did not induce further DNA strand breaks (COMET assay) compared to untreated controls; however, an increase was measured with both 80:20 and 20:80 EtOH:dH 2 O RSP extracts. The anti-cancer properties of RSP extracts demonstrated in this study warrant further investigation and, potentially, open new avenues for the identification of chemo-preventative agents and reutilisation/revalorisation of rapeseed pomace. [ABSTRACT FROM AUTHOR]