Oxidized low-density lipoprotein (oxLDL)-induced endothelium injury promotes the development of atherosclerosis. It has been reported that homoplantaginin, a flavonoid glycoside from the traditional Chinese medicine Salvia plebeia R. Br., protected vascular endothelial cells by inhibiting inflammation. However, it is undetermined whether homoplantaginin affects atherosclerosis. In this study, we evaluated the effect of homoplantaginin and its derivative dihydrohomoplantagin on oxLDL-induced endothelial cell injury and atherosclerosis in apoE-/- mice. Our results showedthat both dihydrohomoplantagin and homoplantaginin inhibited apoptosis and the increased level of ICAM-1 and VCAM-1 in oxLDL-stimulated HUVECs and the plaque endothelium of apoE-/- mice. Additionally, both of them restricted atherosclerosis development of apoE-/- mice. Mechanistic studies showed that oxLDL-induced the increase in ROS production, phosphorylation of ERK and nuclear translocation of NF-κB in HUVECs was significantly inhibited by the compounds. Meanwhile, these two compounds promoted Nrf2 nuclear translocation and increased the anti-oxidation downstream HO-1 protein level in HUVECs and plaque endothelium. Notably, knockdown of Nrf2 by siRNA abolished the cell protective effects of compounds and antagonized the inhibition effects of them on ROS production and NF-κB activation in oxLDL-stimulated HUVECs. Collectively, dihydrohomoplantagin and homoplantaginin protected VECs by activating Nrf2 and thus inhibited atherosclerosis in apoE-/- mice. Full article

Four stereoisomeric monoether derivatives, based on axially chiral (R)- or (S)-BINOL bearing a chiral (+)- or (−)-neomenthyloxy group were synthesised and fully characterised by NMR spectroscopy and X-ray crystallography. The respective tris-monophosphites were thereof prepared and fully characterised. The coordination ability of the new bulky phosphites with Rh(CO)₂(acac), was attested by ³¹P NMR, which presented a doublet in the range of δ = 120 ppm, with a ¹J(¹⁰³Rh-³¹P) coupling constant of 290 Hz. The new tris-binaphthyl phosphite ligands were further characterised by DFT computational methods, which allowed us to calculate an electronic (CEP) parameter of 2083.2 cm⁻¹ and an extremely large cone angle of 345°, decreasing to 265° upon coordination with a metal atom. Furthermore, the monophosphites were applied as ligands in rhodium-catalysed hydroformylation of styrene, leading to complete conversions in 4 h, 100% chemoselectivity for aldehydes and up to 98% iso-regioselectivity. The Rh(I)/phosphite catalytic system was also highly active and selective in the hydroformylation of disubstituted olefins, including (E)-prop-1-en-1-ylbenzene and prop-1-en-2-ylbenzene. Full article

In just a few years, chemists have significantly changed their approach to the synthesis of organic molecules in the laboratory and industry. Researchers are encouraged to approach “greener” reagents, solvents, and methodologies, to go hand in hand with the world’s environmental matter, such as water, soil, and air pollution. The employment of plant and animal derivates that are commonly regarded as “waste material” has paved the way for the development of new green strategies. In this review, the most important innovations in this field have been highlighted, paying due attention to those materials that have played a crucial role in organic reactions: wool, silk, and feather. Moreover, we decided to focus on the other most important supports and catalysts in green syntheses, such as proteins and their derivates. Different materials have shown prominent activity in the adsorption of metals and organic dyes, which has constituted a relevant scope in the last two decades. We intend to furnish a complete screening of the application given to these materials and contribute to their potential future utilization. Full article

Apple industrial by-products are a promising source of bioactive compounds with direct implications on human health. The main goal of the present work was to characterize the Jonathan and Golden Delicious by-products from their fatty acid, amino acid, and volatile aroma compounds’ point of view. GC-MS (gas chromatography-mass spectrometry) and ITEX/GC-MS methods were used for the by-products characterization. Linoleic and oleic were the main fatty acids identified in all samples, while palmitic and stearic acid were the representant of saturated ones. With respect to amino acids, from the essential group, isoleucine was the majority compound identified in JS (Jonathan skin) and GS (Golden skin) samples, lysine was the representant of JP (Jonathan pomace), and valine was mainly identified in GP (Golden pomace). A total number of 47 aroma volatile compounds were quantified in all samples, from which the esters groups ranged from 41.55–53.29%, aldehydes 29.75–43.99%, alcohols from 4.15 to 6.37%, ketones 4.14–5.72%, and the terpenes and terpenoids group reached values between 2.27% and 4.61%. Moreover, the by-products were valorized in biscuits manufacturing, highlighting their importance in enhancing the volatile aroma compounds, color, and sensorial analysis of the final baked goods. Full article

Processing technique and storage conditions are the main factors that affect the phytochemical profile of Not-from-Concentrate (NFC) juice, which could decrease the nutritional and bioactive properties of the corresponding juice. The aim of this study was to evaluate the quality changes that occurred in NFC mango juice after Ohmicsonication (OS) and during storage in comparison to other processing methods such as sonication (S), thermosonication (TS), ohmic heating (OH), and conventional heating (CH). Quality attributes such as polyphenoloxidase (PPO) and pectinmethylesterase (PME) activities, ascorbic acid and hydroxymethyl furfural (HMF) contents, total phenolics, total flavonoids, total carotenoids, electric conductivity, color values and microbial load (total plate count, mold, yeast, and psychrophilic bacteria) were examined. OS and OH treatments demonstrated the highest inactivation of PPO (100%), while CH and TS displaying inhibitions 89% and 90%, respectively and only S treatment exhibited insufficient inactivation of both PPO and microbial load. However, the inhibition of PME followed the order OS (96.5%) > OH (94.9%) > TS (92.5%) > CH (88.5%). The best treatment, with the highest retention of phytochemical contents (ascorbic acid, total carotenoids, antioxidant activity, total flavonoids, and total phenolic content) for NFC mango juice and during storage was obtained with OS treated samples compared to other treatments (in the order from the lowest to highest percentage, OS < OH < TS < CH). Consequently, the results indicated that OS could be applied as a new mild thermal treatment in the production of mango juice with improved quality properties of stored NFC mango juice. Full article

The notion of a contribution of a specific group in an organic molecule’s property and/or activity is both common in our thinking and is still not strictly correct due to the inherent non-additivity of free energy with respect to molecular fragments composing a molecule. The fragment- based drug discovery (FBDD) approach has proven to be fruitful in addressing the above notions. The main difficulty of the FBDD, however, is in its reliance on the low throughput and expensive experimental means of determining the fragment-sized molecules binding. In this article we propose a way to enhance the throughput and availability of the FBDD methods by judiciously using an in silico means of assessing the contribution to ligand-receptor binding energy of fragments of a molecule under question using a previously developed in silico Reverse Fragment Based Drug Discovery (R-FBDD) approach. It has been shown that the proposed structure-based drug discovery (SBDD) type of approach fills in the vacant niche among the existing in silico approaches, which mainly stem from the ligand-based drug discovery (LBDD) counterparts. In order to illustrate the applicability of the approach, our work retrospectively repeats the findings of the use case of an FBDD hit-to-lead project devoted to the experimentally based determination of additive group efficiency (GE)—an analog of ligand efficiency (LE) for a group in the molecule—using the Free-Wilson (FW) decomposition. It is shown that in using our in silico approach to evaluate fragment contributions of a ligand and to estimate GE one can arrive at similar decisions as those made using the experimentally determined activity-based FW decomposition. It is also shown that the approach is rather robust to the choice of the scoring function, provided the latter demonstrates a decent scoring power. We argue that the proposed approach of in silico assessment of GE has a wider applicability domain and expect that it will be widely applicable to enhance the net throughput of drug discovery based on the FBDD paradigm. Full article

In the present study, we confirmed that α-asaronol, which is a product of the active metabolites of alpha Asarone, did not affect n-butylphthalide efficacy when n-butylphthalide and α-asaronol were co-administered to rats with cerebral ischemia-reperfusion injury. Our research revealed that the co-administration of α-asaronol and n-butylphthalide could further improve neurological function, reduce brain infarct volume, increase the number of Nissl bodies, and decrease the ratios of apoptotic cells and the expression of the caspase-3 protein for cerebral ischemia-reperfusion injury model compared to n-butylphthalide alone. Additionally, α-asaronol could significantly decrease the incidence of post-stroke epilepsy versus n-butylphthalide. This study provides valuable data for the follow-up prodrug research of α-asaronol and n-butylphthalide. Full article

Bile acids are important physiological agents required for the absorption, distribution, metabolism, and excretion of nutrients. In addition, bile acids act as sensors of intestinal contents, which are determined by the change in the spectrum of bile acids during microbial transformation, as well as by gradual intestinal absorption. Entering the liver through the portal vein, bile acids regulate the activity of nuclear receptors, modify metabolic processes and the rate of formation of new bile acids from cholesterol, and also, in all likelihood, can significantly affect the detoxification of xenobiotics. Bile acids not absorbed by the liver can interact with a variety of cellular recipes in extrahepatic tissues. This provides review information on the synthesis of bile acids in various parts of the digestive tract, its regulation, and the physiological role of bile acids. Moreover, the present study describes the involvement of bile acids in micelle formation, the mechanism of intestinal absorption, and the influence of the intestinal microbiota on this process. Full article

Dalbergia sissoo is a woody plant with economic and medicinal value. As the pharmacological qualities and properties of the wood from this plant primarily depend on its extractives, in this study, the metabolomic analysis of extractives from its stems was carried out using UPLC-MS/MS. A total of 735 metabolites were detected from two groups of samples, heartwood and sapwood, with the largest number of terpenoids in type and the largest number of flavonoids in quantity. The PCA and cluster analysis showed significant differences in the metabolite composition between the two groups. The differential metabolites were mainly organic oxygen compounds, flavonoids, and isoflavones. Among the 105 differential metabolites, 26 metabolites were significantly higher in relative content in sapwood than in heartwood, while the other 79 metabolites were significantly higher in relative content in heartwood than in sapwood. KEGG metabolic pathway enrichment analysis showed that these differential metabolites were mainly enriched in three metabolic pathways: Flavonoid biosynthesis, isoflavonoid biosynthesis, and flavonoid and flavonol biosynthesis. This study provides a reference for metabolomics studies in Dalbergia and other woody plants. Full article

This study investigated the antioxidant, antimicrobial, anticancer, and phytochemical profiling of extracts from the leaves and stem/root of Acanthus ebracteatus (AE). The total phenolic content (TPC), total flavonoid content (TFC), 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radical-scavenging activity, 2, 2′-azino-Bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical-scavenging activity, metal chelating activities (MCA), ferric reducing antioxidant power (FRAP) and oxygen radical antioxidant capacity (ORAC) were used for antioxidant assessment. The ethanolic extracts of the leaves (AEL-nor) and stem/root (AEWP-nor) without chlorophyll removal and those with chlorophyll removal, using sedimentation process (AEL-sed and AEWP-sed), were prepared. Generally, AEL-sed showed the highest antioxidant activity (FRAP: 1113.2 µmol TE/g; ORAC: 11.52 µmol TE/g; MCA: 47.83 µmol EDTA/g; ABTS 67.73 µmol TE/g; DPPH 498.8 µmol TE/g; TPC: 140.50 mg/GAE g and TFC: 110.40 mg/CE g) compared with other extracts. Likewise, AEL-sed also showed the highest bacteriostatic (MIC) and bactericidal (MBC) effects, as well as the highest anticancer and antiproliferative activity against oral squamous carcinoma (CLS-354/WT) cells. UPLC-ESI-QTOF/MS analysis of AEL-sed and AEWP-sed tentatively identified several bioactive compounds in the extracts, including flavonoids, phenols, iridoids, and nucleosides. Our results provide a potentially valuable application for A. ebracteatus, especially in further exploration of the plant in oxidative stress-related disorders, as well as the application of the plant as potential nutraceuticals and cosmeceuticals. Full article

This work presents a palladium-catalyzed oxime ether-directed ortho-selective benzoylation using benzoylformic acid as the acyl source with a palladium catalyst and 4CzIPN as the co-catalyst under light. Various non-symmetric benzophenone derivatives were obtained in moderate to good yields. A preliminary mechanism study revealed that the reaction proceeds through a free radical pathway. Full article

Cathissa reverchonii (formerly Ornithogalum reverchonii) is a threatened species, constituting an endemism present in the south of Spain and northern Morocco. In Spain, it is only found in two disjoint populations in the region of Andalusia. The determination of its chemical composition and the influence that environmental factors have on it can contribute significantly to the development of appropriate protection and conservation plans. However, there are no previous reports about this species to date. Consequently, this research aimed to study the phenolic composition and antioxidant activity of C. reverchonii and to assess the influence of environmental factors on the phenolic profile and bioactivity. The vegetal material was collected in seven places inhabited by the two separate populations in Spain. The phenolic composition of methanolic extracts of the species was determined by HPLC-ESI-Q-TOF-MS, and the antioxidant activity was assessed by DPPH and ABTS assays. Fifteen compounds were characterized in the extracts of the aerial parts of C. reverchonii, revealing differences in the phytochemical profile between both populations analyzed, mainly in the saponin fraction. The main phenolics were flavone di-C-glucoside (lucenin-2), followed by a quercetin-di-C-glucoside. The composition of the extracts of C. reverchonii and their radical scavenging power were compared with those of other species of the genus Ornithogalum L., revealing significant differences between the latter and the genus Cathissa. Full article

Garcinia biflavonoid 1 (GB1) is one of the active chemical components of Garcinia kola and is reported to be capable of reducing the intracellular lipid deposition, which is the most significant characteristic of non-alcoholic fatty liver disease. However, its bioactive mechanism remains elusive. In the current study, the lipid deposition was induced in HepG2 cells by exposure to oleic acid and palmitic acid (OA&PA), then the effect of GB1 on lipid metabolism and oxidative stress and the role of regulating PPARα in these cells was investigated. We found that GB1 could ameliorate the lipid deposition by reducing triglycerides (TGs) and upregulate the expression of PPARα and SIRT6, suppressing the cell apoptosis by reducing the oxidative stress and the inflammatory factors of ROS, IL10, and TNFα. The mechanism study showed that GB1 had bioactivity in a PPARα-dependent manner based on its failing to improve the lipid deposition and oxidative stress in PPARα-deficient cells. The result revealed that GB1 had significant bioactivity on improving the lipid metabolism, and its potential primary action mechanism suggested that GB1 could be a potential candidate for management of non-alcoholic fatty liver disease. Full article

ARV-110, a novel proteolysis-targeting chimera (PROTAC), has been reported to show satisfactory safety and tolerability for prostate cancer therapy in phase I clinical trials. However, there is a lack of bioanalytical assays for ARV-110 determination in biological samples. In this study, we developed and validated an LC-MS/MS method for the quantitation of ARV-110 in rat and mouse plasma and applied it to pharmacokinetic studies. ARV-110 and pomalidomide (internal standard) were extracted from the plasma samples using the protein precipitation method. Sample separation was performed using a C18 column and a mobile phase of 0.1% formic acid in distilled water–0.1% formic acid in acetonitrile (30:70, v/v). Multiple reaction monitoring was used to quantify ARV-110 and pomalidomide with ion transitions at m/z 813.4 → 452.2 and 273.8 → 201.0, respectively. The developed method showed good linearity in the concentration range of 2–3000 ng/mL with acceptable accuracy, precision, matrix effect, process efficiency, and recovery. ARV-110 was stable in rat and mouse plasma under long-term storage, three freeze-thaw cycles, and in an autosampler, but unstable at room temperature and 37 °C. Furthermore, the elimination of ARV-110 via phase 1 metabolism in rat, mouse, and human hepatic microsomes was shown to be unlikely. Application of the developed method to pharmacokinetic studies revealed that the oral bioavailability of ARV-110 in rats and mice was moderate (23.83% and 37.89%, respectively). These pharmacokinetic findings are beneficial for future preclinical and clinical studies of ARV-110 and/or other PROTACs. Full article

Fruit of Saskatoon (Amelanchier alnifolia Nutt.) are a good source of bioactive compounds, such as polyphenols, including anthocyanins, as well as vitamins, macro- and microelements and fibre. By treating Saskatoon fruits with gaseous ozone, and adding the material as an enhancer to barley beers, it is possible to impact the contents of bioactive compounds in the produced fruit beers. Sensory tests showed that beers made from barley with addition of Saskatoon fruit of the ‘Smoky’ cultivar were characterised by the most balanced taste and aroma. Physicochemical analyses of fruit beers, produced with Saskatoon fruit pulp added on the seventh day of fermentation, showed that the beers enhanced with ozone-treated and untreated ‘Smoky’ Saskatoon fruits had the highest contents of alcohol, 5.51% v/v and 5.66% v/v, respectively, as well as total polyphenol contents of 395 mg GAE/L and 401 mg GAE/L, respectively, and higher antioxidant activity (assessed using DPPH^•, FRAP and ABTS^+• assays). It was demonstrated that the ozonation process led to a decrease in the contents of neochlorogenic acid, on average by 91.00%, and of caffeic acid by 20.62%, relative to the beers enhanced with ‘Smoky’ Saskatoon fruits not subjected to ozone treatment. The present study shows that Saskatoon fruits can be used in the production of beer, and the Canadian cultivar ‘Smoky’ is recommended for this purpose. Full article