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The heterocyclic ring system of pyrido [2,3-d]pyrimidines is a privileged scaffold in medicinal chemistry, possessing several biological activities. The synthesis of the pyrimidine derivatives was performed via the condensation of a suitable α,β-unsaturated ketone with 4-amino-6-hydroxy-2-mercaptopyrimidine monohydrate in glacial acetic acid. Chalcones were synthesized, as starting materials, via the Claisen–Schmidt condensation of an appropriately substituted ketone and an appropriately substituted aldehyde in the presence of aqueous KOH 40% w/v in ethanol. All the synthesized compounds were characterized using IR, 1H-NMR, 13C-NMR, LC-MS and elemental analysis. The synthesized compounds were evaluated for their antioxidant (DPPH assay), anti-lipid peroxidation (AAPH), anti-LOX activities and ability to interact with glutathione. The compounds do not interact significantly with DPPH but strongly inhibit lipid peroxidation. Pyrimidine derivatives 2a (IC50 = 42 μΜ), 2f (IC50 = 47.5 μΜ) and chalcone 1g (IC50 = 17 μM) were the most potent lipoxygenase inhibitors. All the tested compounds were found to interact with glutathione, apart from 1h. Cell viability and cytotoxicity assays were performed with the HaCaT and A549 cell lines, respectively. In the MTT assay towards the HaCaT cell line, none of the compounds presented viability at 100 μM. On the contrary, in the MTT assay towards the A549 cell line, the tested compounds showed strong cytotoxicity at 100 μM, with derivative 2d presenting the strongest cytotoxic effects at the concentration of 50 μΜ. [ABSTRACT FROM AUTHOR]

Background: The Mediterranean diet (MD) is a beneficial dietary pattern with strong antioxidant and anti-inflammatory properties that can promote mental and physical human health. This study aims to assess the impact of MD adherence on health-related quality of life, physical activity levels, and sleep quality in a representative Greek elderly population. Methods: This is a cross-sectional study. A total of 3254 persons ≥65 years from 14 different Greek regions, urban, rural and islands participated in this study, of which 48.4% were female and 51.6% were male. Health-Related Quality of Life (HRQOL) was evaluated utilizing a short form healthy survey, physical activity was determined by the International Physical Activity Questionnaire (IPAQ), sleep quality was assessed utilizing the Pittsburgh Sleep Quality Index (PSQI) and MD adherence was assessed via the Mediterranean Diet Score (MedDietScore). Results: Moderate adherence to the MD and an increased prevalence of poor quality of life, low physical activity levels and inadequate sleep quality among the elderly population were recorded. High MD adherence was independently associated with better quality of life (OR: 2.31, 95% CI: 2.06–2.68, p = 0.0008), higher physical activity (OR: 1.89, 95% CI: 1.47–2.35, p = 0.0141) and adequate sleep quality (OR: 2.11, 95%: 1.79–2.44, p = 0.0018), female sex (OR: 1.36, 95% CI: 1.02–1.68, p = 0.0032) and living with others (OR: 1.24, 95% CI: 0.81–1.76, p = 0.0375), after adjustment for potential confounding factors. In unadjusted analysis, participants' age (p < 0.0001), anthropometric characteristics (p < 0.005), educational (p = 0.0026) and financial status (p = 0.0005) and smoking habits (p = 0.0031) were also identified as indicators of MD adherence; however, their impact on MD adherence was considerably attenuated after adjusting for confounding factors (p > 0.05). Conclusion: High MD adherence was correlated with favorable quality of life, higher levels of physical activity, and a more adequate sleep quality score. Strategies and public health policies that facilitate MD adherence and physical activity in older adults may improve sleep and quality of life, impacting overall wellbeing in this age group. [ABSTRACT FROM AUTHOR]

The synthesis of several novel coumarin derivatives with a 7-azomethine linkage was carried out starting from 7-formyl-coumarin. The compounds were tested in vivo for their anti-inflammatory activity and in vitro for their antioxidant ability. Compounds 3a and 3e possess significant protection against carrageenin induced rat paw edema. [Copyright &y& Elsevier]

Rheumatoid arthritis (RA) is an autoimmune disorder affecting a vast variety of the population. The onset of RA as well as the development of systematic immunization is affected by both genetic and environmental risk factors. This review aims to point out the role of natural products in the management of RA, focusing on the reports of basic research (in vitro and animal studies) emphasizing the antioxidant and anti-inflammatory properties considered in the field of RA. A systematic screening of the relevant literature was carried out on PubMed, Google Scholar, and Scopus with the following criteria: publication date, 2015–2020; language, English; study design, in vitro or animal models; and the investigation of one or several natural products in the context of RA, including, when available, the molecular mechanisms implicated. A total of 211 papers were initially obtained and screened. In vitro and animal studies referring to 20 natural products and 15 pure compounds were ultimately included in this review. The outcomes of this work provide an overview of the methods employed in basic research over the past five years, with emphasis on the limitations presented, while demonstrating the potential benefits of utilizing natural products in the management of RA as supported by in vitro and animal studies. [ABSTRACT FROM AUTHOR]

Oligonol is a low molecular weight polyphenol product derived from lychee fruit by a manufacturing process. We investigated oligonol's anti-fibrotic effect and the underlying mechanism in dimethylnitrosamine (DMN)-induced chronic liver damage in male Sprague–Dawley rats. Oral administration of oligonol (10 and 20 mg/kg body weight) ameliorated the DMN-induced abnormalities in liver histology and serum parameters in rats. Oligonol prevented the DMN-induced elevations of TNF-α, IL-1β, IL-6, cyclooxygenase-2, and inducible nitric oxide synthase expressions at the mRNA level. NF-κB activation and JNK phosphorylation in DMN-treated rats were ablated by oligonol. Oligonol reduced the enhanced production of hepatic malondialdehyde and reactive oxygen species and recovered protein SH, non-protein SH levels, and catalase activity in the DMN treated liver. Nrf2 translocation into the nucleus was enhanced, and PI3K and phosphorylated Akt levels were increased by administering oligonol. The level of hepatic fibrosis-related factors such as α-smooth muscle actin, transforming growth factor-β1, and type I collagen was reduced in rats treated with oligonol. Histology and immunohistochemistry analysis showed that the accumulation of collagen and activation of hepatic stellate cells (HSCs) in liver tissue were restored by oligonol treatment. Taken together, oligonol showed antioxidative, hepatoprotective, and anti-fibrotic effects via JNK/NF-κB and PI3K/Akt/Nrf2 signaling pathways in DMN-intoxicated rats. These results suggest that antioxidant oligonol is a potentially useful agent for the protection against chronic liver injury. [ABSTRACT FROM AUTHOR]

The natural process of aging gradually causes changes in living organisms, leading to the deterioration of organs, tissues, and cells. In the case of osteoarthritis (OA), the degradation of cartilage is a result of both mechanical stress and biochemical factors. Natural products have already been evaluated for their potential role in the prevention and treatment of OA, providing a safe and effective adjunctive therapeutic approach. This review aimed to assess the therapeutic potential of natural products and their derivatives in osteoarthritis via a systematic search of literature after 2008, including in vitro, in vivo, ex vivo, and animal models, along with clinical trials and meta-analysis. Overall, 170 papers were obtained and screened. Here, we presented findings referring to the preventative and therapeutic potential of 17 natural products and 14 naturally occurring compounds, underlining, when available, the mechanisms implicated. The nature of OA calls to initially focus on the management of symptoms, and, in that context, several naturally occurring compounds have been utilized. Underlying a global need for more sustainable natural sources for treatment, the evidence supporting their chondroprotective potential is still building up. However, arriving at that kind of solution requires more clinical research, targeting the implications of long-term treatment, adverse effects, and epigenetic implications. [ABSTRACT FROM AUTHOR]

Abstract: In the present work a series of novel coumarin-3-carboxamides and their hybrids with the alpha-lipoic acid were designed, synthesized and tested as potent antioxidant and anti-inflammatory agents. The new compounds were evaluated for their antioxidant activity, their activity to inhibit in vitro lipoxygenase and their in vivo anti-inflammatory activity. In general, the derivatives were generally found to present antioxidant and anti-inflammatory activities. Discussion is made based on the results for the structure–activity relationships in order to define the structural features required for activity. [Copyright &y& Elsevier]