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Prions are infectious protein particles known to cause prion diseases. The biochemical entity of the pathogen is the misfolded prion protein (PrPSc) that forms insoluble amyloids to impair brain function. PrPSc interacts with the non-pathogenic, cellular prion protein (PrPC) and facilitates conversion into a nascent misfolded isoform. Several small molecules have been reported to inhibit the aggregation of PrPSc but no pharmacological intervention was well established thus far. We, here, report that acylthiosemicarbazides inhibit the prion aggregation. Compounds 7x and 7y showed almost perfect inhibition (EC50 = 5 µM) in prion aggregation formation assay. The activity was further confirmed by atomic force microscopy, semi-denaturing detergent agarose gel electrophoresis and real-time quaking induced conversion assay (EC50 = 0.9 and 2.8 µM, respectively). These compounds also disaggregated pre-existing aggregates in vitro and one of them decreased the level of PrPSc in cultured cells with permanent prion infection, suggesting their potential as a treatment platform. In conclusion, hydroxy-2-naphthoylthiosemicarbazides can be an excellent scaffold for the discovery of anti-prion therapeutics.

Inflammatory bowel disease (IBD) is a chronic immuno-inflammation in gastrointestinal tract. We have evaluated the activity of the compounds to inhibit the adhesion of monocytes to colon epithelial cells is triggered by a pro-inflammatory cytokine, tumour necrosis factor (TNF)-α. The in vitro activity of the compounds, 13b (an ureido-derivative), 14c, 14j, 14k, 14n (thioureido-), 18c and 18d (sulfonamido-), was in correlation with in vivo anti-colitis activity revealed as significant recovery in body- and colon-weights and colon myeloperoxidase level, a biochemical marker of inflammation reflecting neutrophil infiltration. In vivo, TNBS-induced changes in the expression of inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-10, and TGF-β), NLRP3 inflammasome components (NLRP-3, Caspase-1, and IL-18), and epithelial junction molecules (E-cadherin, claudin2/3, and ZO-1) were blocked and recovered by oral administration of the compounds (1 mg/kg). Compound 14n which showed the best efficacy can be a promising lead for orally available therapeutics for pathology of IBD.

Hypervalent iodine-mediated olefin functionalization provides a rapid gateway towards accessing both various heterocyclic cores and functional groups. In this regard, we have developed a Ritter-type alkene functionalization utilizing a PhI(OAc)2 ((diacetoxyiodo)benzene, PIDA)/Lewis acid combination in order to access isoxazoline and pyrazoline cores. Based on allyl ketone oximes and allyl ketone tosylhydrazones, we have developed an alkene oxyamidation and amido-amidation protocol en route to accessing both isoxazoline and pyrazoline cores. Additionally, acetonitrile serves as both the solvent and an amine source in the presence of this PIDA/Lewis acid combination. This operationally straightforward and metal-free protocol provides an easy access to isoxazoline and pyrazoline derivatives.

Rosa gallica is a widely used Rosa species for medicinal and culinary purposes. Rosa gallica has been reported to display antioxidant, anti−inflammatory, and antibacterial activities. However, the effect of Rosa gallica against skin aging in vivo is unknown and its active components have not been fully understood. Oral administration of Rosa gallica prevented UVB−mediated skin wrinkle formation and loss of collagen/keratin fibers in the dorsal skin of mice. Examination of biomarkers at the molecular level showed that Rosa gallica downregulates UVB−induced COX−2 and MMP−1 expression in the skin. Through a direct comparison of major compounds identified using the UHPLC−MS/MS system, we discovered gallic acid as the primary component contributing to the anti-skin aging effect exhibited by Rosa gallica. Examination of the molecular mechanism revealed that gallic acid can potently and selectively target the c−Raf/MEK/ERK/c−Fos signaling axis. In addition, both gallic acid and MEK inhibitor blocked UVB−induced MMP−1 expression and restored collagen levels in a reconstructed 3D human skin model. Collectively, Rosa gallica could be used as a functional ingredient in the development of nutraceuticals against skin aging.

α-Flavone glycosides have beneficial properties for applications in the pharmaceutical, cosmetic, and food industries. However, their chemical syntheses are often limited by a low efficiency or scarcity of substrates. In this study, α-flavone glucosides were enzymatically synthesized by amylosucrase from Deinococcus geothermalis (DGAS) using sucrose and various flavones as a donor for glucosyl units and acceptors, respectively. Luteolin was the most effective acceptor in the transglucosylation reaction using DGAS among nine flavone materials (apigenin, chrysin, 6,7-dihydroxyflavone, homoorientin, 7-hydroxyflavone, isorhoifolin, luteolin, luteolin-3',7-diglucoside, and orientin). The highest production yield of luteolin glucoside was 86%, with a 7:1 molar ratio of donor to acceptor molecules, in 50 mM Tris-HCl buffer (pH 7) at 37°C for 24 h using 2 U of DGAS. The synthesized luteolin glucoside was identified as luteolin-4'-O-α-D-glucopyranoside with a glucose molecule linked to the C-4' position on the B-ring of luteolin via an α-glucosidic bond, as determined by 1H and 13C nuclear magnetic resonance. This result clearly confirmed that the glucosylated luteolin was successfully synthesized by DGAS and it can be applied as a functional ingredient. Furthermore, this approach using DGAS has the potential to be utilized for the synthesis of various glucosylated products using different types of polyphenols to enhance their functionalities.

CD4+ T cells are essential in inflammation and autoimmune diseases. Interferon-γ (IFN-γ) secreting T helper (Th1) and IL-17 secreting T helper (Th17) cells are critical for several autoimmune diseases. To assess the inhibitory effect of a given compound on autoimmune disease, we screened many compounds with an in vitro Th differentiation assay. BJ-3105, a 6-alkoxypyridin-3-ol analog, inhibited IFN-γ and IL-17 production from polyclonal CD4+ T cells and ovalbumin (OVA)-specific CD4+ T cells which were activated by T cell receptor (TCR) engagement. BJ-3105 ameliorated the experimental autoimmune encephalomyelitis (EAE) model by reducing Th1 and Th17 generation. Notably, Th cell differentiation was significantly suppressed by BJ-3105 treatment without inhibiting in vitro proliferation of T cells or inducing programmed cell death. Mechanistically, BJ-3105 inhibited the phosphorylation of JAK and its downstream signal transducer and activator of transcription (STAT) that is critical for Th differentiation. These results demonstrated that BJ-3105 inhibits the phosphorylation of STAT in response to cytokine signals and subsequently suppressed the differentiation of Th cell responses.

5-Hydroxytryptamine (5-HT) induces proliferation of cancer cells and vascular cells. In addition to 5-HT production by several cancer cells including gastrointestinal and breast cancer, a significant level of 5-HT is released from activated platelets in the thrombotic environment of tumors, suggesting that inhibition of 5-HT signaling may constitute a new target for antiangiogenic anticancer drug discovery. In the current study we clearly demonstrate that 5-HT-induced angiogenesis was mediated through the 5-HT1 receptor-linked Gβγ/Src/PI3K pathway, but not through the MAPK/ERK/p38 pathway. In addition, 5-HT induced production of NADPH oxidase (NOX)-derived reactive oxygen species (ROS). In an effort to develop new molecularly targeted anticancer agents against 5-HT action in tumor growth, we demonstrate that BJ-1108, a derivative of 6-amino-2,4,5-trimethylpyridin-3-ol, significantly inhibited 5-HT-induced angiogenesis. In addition, BJ-1108 induced a significant reduction in the size and weight of excised tumors in breast cancer cell-inoculated CAM assay, showing proportionate suppression of tumor growth along with inhibition of angiogenesis. In human umbilical vein endothelial cells (HUVECs), BJ-1108 significantly suppressed 5-HT-induced ROS generation and phosphorylation of PI3K/Akt but not of Src. Unlike NOX inhibitors, BJ-1108, which showed better antioxidant activity than vitamin C, barely suppressed superoxide anion induced by mevalonate or geranylgeranyl pyrophosphate which directly activates NOX without help from other signaling molecules in HUVECs, implying that the anti-angiogenic action of BJ-1108 was not mediated through direct action on NOX activation, or free radical scavenging activity. In conclusion, BJ-1108 inhibited 5-HT-induced angiogenesis through PI3K/NOX signaling but not through Src, ERK, or p38.

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Glutamate is the major excitatory neurotransmitter in the brain. It can cause neuronal cell damage in the context of oxidative stress. BJ-1201 is a derivative of the compound aminopyridinol, which is known for its antioxidant activity. In this study, we examined the effect of BJ-1201, a 6-(diphenylamino)-2,4,5-trimethylpyridin-3-ol compound, on neuroprotection in HT22 cells. Our data showed that BJ-1201 can protect HT22 cells against glutamate-induced cell cytotoxicity. In addition, BJ-1201 upregulated heme oxygenase-1 (HO-1) to levels comparable to those of the CoPP-treated group. BJ-1201 treatment induced phosphorylation of JNK, but not p38-MAPK or ERK. It also increased the signal in the reporter assay based on β-galactosidase activity driven by the nuclear transcription factor erythroid-2 related factor 2 (Nrf2) promoter harboring antioxidant response elements (AREs) and induced the translocation of Nrf2. These results demonstrate that BJ-1201 may be a good therapeutic platform against neurodegenerative diseases induced by oxidative stress.

Abstract Background CD4+ T cells play an important role in the initiation of an immune response by providing help to other cells. Among the helper T subsets, interferon-γ (IFN-γ)-secreting T helper 1 (Th1) and IL-17-secreting T helper 17 (Th17) cells are indispensable for clearance of intracellular as well as extracellular pathogens. However, Th1 and Th17 cells are also associated with pathogenesis and contribute to the progression of multiple inflammatory conditions and autoimmune diseases. Results In the current study, we found that BJ-1108, a 6-aminopyridin-3-ol analogue, significantly inhibited Th1 and Th17 differentiation in vitro in a concentration-dependent manner, with no effect on proliferation or apoptosis of activated T cells. Moreover, BJ-1108 inhibited differentiation of Th1 and Th17 cells in ovalbumin (OVA)-specific OT II mice. A complete Freund’s adjuvant (CFA)/OVA-induced inflammatory model revealed that BJ-1108 can reduce generation of proinflammatory Th1 and Th17 cells. Furthermore, in vivo studies showed that BJ-1108 delayed onset of disease and suppressed experimental autoimmune encephalomyelitis (EAE) disease progression by inhibiting differentiation of Th1 and Th17 cells. Conclusions BJ-1108 treatment ameliorates inflammation and EAE by inhibiting Th1 and Th17 cells differentiation. Our findings suggest that BJ-1108 is a promising novel therapeutic agent for the treatment of inflammation and autoimmune disease.

Abstract The simultaneous determination of trace pesticides in complex matrices containing high concentrations of natural pigments remains challenging. In this study, quick, easy, cheap, effective, rugged, and safe (QuEChERS) sample preparation together with high-performance liquid chromatography with ultraviolet detection (HPLC–UV) was applied for the multi-residue analysis of seven sulfonylurea herbicides (SUHs) in tomatoes. SUH residue was extracted using the QuEChERS procedure, followed by solid-phase extraction (SPE) and dispersive SPE (d-SPE). To reduce the amount of carotenoids in tomato extracts, several d-SPE clean-up procedures were compared, and octadecylsilane (C18) provided the best color removal rate (%) of tomato extracts and recoveries (%) for all the tested SUHs. The validation results indicate good linearity (R2 > 0.9970), accuracy, and precision. Recoveries of 70–120% and relative standard deviations

Glyoxal, methylglyoxal, and diacetyl are toxic α-dicarbonyl compounds found in heat-processed foods, including edible oils. Dispersive liquid–liquid microextraction was combined with gas chromatography mass spectrometry to determine the glyoxal, methylglyoxal, and diacetyl contents in sesame oil. Chloroform and methanol were selected as the optimal extraction and dispersive solvents, respectively. The maximum derivatization efficiency was obtained using 500 µg of the derivatization agent, o-phenylenediamine. The derivatization of glyoxal was completed in 1 h, whereas those of methylglyoxal and diacetyl were completed immediately. The optimized method was validated, and was found to exhibit a good linearity, recovery, intraday repeatability, and interday reproducibility. The α-dicarbonyl compound concentrations in the oils were dependent on the roasting temperature. The sesame oil concentrates contained 0–175.4, 0–990.5, and 0–220.9 ng g−1 of glyoxal, methylglyoxal, and diacetyl, respectively. For the perilla oils, the respective concentrations were 0–96.4, 0–410.8, and 0–197.5 ng g−1.

Herein, a QuEChERS (quick, easy, cheap, effective, rugged, and safe) procedure together with liquid chromatography and tandem mass spectrometry was applied to the multi-residue analysis of 203 pesticides in strawberries. To reduce the amount of co-eluents, we compared several dispersive solid-phase extraction cleanup procedures and found that cleanup using octadecylsilane provided the best recoveries. Spiked-sample recoveries of 70–120% with relative standard deviations of 0.99), and the limits of quantification (LOQs) were lower than the maximum residue limits recommended by the European Commission and Korea Food and Drug Administration. The developed method was applied to real samples, revealing that their pesticide contents exceeded the corresponding LOQs. The obtained results demonstrate that octadecylsilane-based dispersive solid-phase extraction is a rapid and high-throughput cleanup procedure for the multi-residue analysis of pesticides in strawberries.

The ability to readily determine the composition of brown rice vinegar is important for quality assurance purposes. To that end, solid–phase microextraction (SPME)–Arrow method was optimized for the determination of volatile organic compounds (VOCs) from brown rice vinegar. Compared to traditional SPME fibers, SPME–Arrow has a larger sorbent-phase volume and is more durable. The SPME–Arrow conditions, including coating material, extraction temperature, extraction time, and NaCl concentration, were examined, which led to optimum extraction conditions that include: carboxen/polydimethylsiloxane (CAR/PDMS) fiber, 50°C, 30 min of SPME–Arrow, and 0% NaCl (i.e., no added NaCl). The developed method was compared to an optimized method based on conventional SPME. Twelve major VOCs, including acetates, alcohols, aldehydes, acids, and furan derivatives, were extracted by SPME–Arrow, while only seven VOCs were extracted using the traditional SPME. Moreover, SPME–Arrow extracted more 1.3–2 times more VOCs than SPME. Hence, the CAR/PDMS SPME–Arrow fiber is suitable for acquiring VOC profiles from brown rice vinegar.

The positive effects of Actinidia eriantha cv. Bidan extract (AEE) were investigated in terms of improvement in Aβ1-42-induced cognitive impairment. AEE was shown to have neuroprotective effects, such as reduction in intracellular reactive oxygen species levels and suppression of apoptotic cell death, in neuron-like PC-12 cells. Results of the in vivo experiment showed that AEE at 200 and 1,000 mg/kg body weight/day, and even at 50 mg/kg body weight/day, reduced impairments in learning and spatial memory in Aβ1-42-treated ICR mice. Furthermore, the endogenous antioxidant systems (SOD, CAT, and GSH/GSSG) in the mouse brain tissue significantly (p < 0.05) increased by AEE administration compared with the group treated with only Aβ1-42. In the analysis of UPLC-Q-TOF mass spectrometry, caffeic acid derivatives such as caffeoylquinic acids were identified in AEE. These results suggest that the Bidan kiwifruit is a good source of antioxidant phenolics that hold the potential to improve cognitive function.

Ginseng (Panax ginseng Meyer) is widely used to treat various chronic disorders. Black ginseng is obtained by repeated steaming and drying of raw ginseng, which turn it black and convert the ginsenoside compounds present into more potent bioactive ingredients. The effects of a black ginseng extract on melanin production and skin whitening were evaluated in vitro as well as in vivo using human skin and zebrafish embryos. Tyrosinase activity decreased when steamed and dried ginseng was used. A pronounced skin-whitening effect was observed in our clinical study, and inhibition of melanin activity and tyrosinase levels was confirmed in zebrafish embryos. Two ginsenosides specific to black ginseng activate the MEK-ERK signaling pathway and are the main factors responsible for skin whitening. The skin-whitening effects of black ginseng are associated with the formation of two ginsenosides, indicating that black ginseng can be used as a novel skin-whitening agent in cosmetic products.

Sesame oil is a high-value edible vegetable oil, and concern about its authenticity has gained much attention for commercial and consumer health reasons. The present study compares the application of triacylglycerols (TAGs), fatty acids, and volatile organic compounds (VOCs) as markers for discriminating pure sesame oils from those adulterated with corn or soybean oils. The profiles of TAGs, fatty acids, and VOCs in oil samples were established by high-performance liquid chromatography-evaporative light scattering detector, gas chromatography (GC)-flame ionization detector, and GC-time-of-flight mass spectrometer, respectively. Data from six TAGs, seven fatty acids, and six VOCs were employed separately to classify oil samples via principal component analysis (PCA). The PCA results indicate that VOCs show much greater promise than TAGs and fatty acids for detecting corn or soybean oil adulteration (approximately 5% w/w content) of sesame oils.

Agricultural water is closely linked to surface and ground water as well as soil; hence, ensuring its safety is an important endeavor. We used the “quick, easy, cheap, effective, rugged, and safe” (QuEChERS) method to analyze multi-residue pesticides in agricultural water by using a combined-sorbent-based clean-up procedure. Among the various sorbents examined, clean-up using ENVI-Carb combined with a primary secondary amine sorbent delivered the highest recovery of multi-residue pesticides (>93.9%). While the developed method showed satisfactory linearity (R2 > 0.9991), precision, and specificity, recovery was low for pyrazolate (29.1%) and thidiazuron (59.2%). The limits of detection and quantification for the 55 pesticides targeted in this study were in 0.02–3.0 μg L−1 and 0.1–9.9 μg L−1, respectively. The developed method was used to identify and quantify multi-residue pesticides during sample analysis. The results suggest that the QuEChERS method employing a combination of ENVI-Carb and another sorbent can be applied for the effective analysis of multi-residue pesticides in agricultural water.

Isoflavones in soybeans are well-known phytoestrogens. Soy isoflavones present in conjugated forms are converted to aglycone forms during processing and storage. Isoflavone aglycones (IFAs) of soybeans in human diets have poor solubility in water, resulting in low bioavailability and bioactivity. Enzyme-mediated glycosylation is an efficient and environmentally friendly way to modify the physicochemical properties of soy IFAs. In this study, we determined the optimal reaction conditions for Deinococcus geothermalis amylosucrase-mediated α-1,4 glycosylation of IFA-rich soybean extract to improve the bioaccessibility of IFAs. The conversion yields of soy IFAs were in decreasing order as follows: genistein > daidzein > glycitein. An enzyme quantity of 5 U and donor:acceptor ratios of 1000:1 (glycitein) and 400:1 (daidzein and genistein) resulted in high conversion yield (average 95.7%). These optimal reaction conditions for transglycosylation can be used to obtain transglycosylated IFA-rich functional ingredients from soybeans.

Ascertaining the authenticity of the unrefined sesame oil presents an ongoing challenge. Here, the determination of 2-propenal was performed by headspace solid-phase microextraction (HS-SPME) under mild temperature coupled to gas chromatography with time-of-flight mass spectrometry, enabling the detection of adulteration of unrefined sesame oil with refined corn or soybean oil. Employing this coupled technique, 2-propenal was detected in all tested refined corn and soybean oils but not in any of the tested unrefined sesame oil samples. Using response surface methodology, the optimum extraction temperature, equilibrium time, and extraction time for the HS-SPME analysis of 2-propenal using carboxen/polydimethylsiloxane fiber were determined to be 55°C, 15 min, and 15 min, respectively, for refined corn oil and 55°C, 25 min, and 15 min, respectively, for refined soybean oil. Under these optimized conditions, the adulteration of unrefined sesame oil with refined corn or soybean oils (1–5%) was successfully detected. The detection and quantification limits of 2-propenal were found to be in the range of 0.008–0.010 and 0.023–0.031 µg mL−1, respectively. The overall results demonstrate the potential of this novel method for the authentication of unrefined sesame oil.

Buckwheat sprouts that are synthesized during the germination process are rich in flavonoids, including orientin, vitexin, rutin, and their isomers (isoorientin, isovitexin, and quercetin-3-O-robinobioside, respectively). The purpose of this study was to optimize and validate an analytical method for separating flavonoid isomers in common buckwheat sprout extract (CSE). Factors, such as range, linearity, precision, accuracy, limit of detection, and limit of quantification, were evaluated for each standard using high-performance liquid chromatography (HPLC). On the basis of resolution and symmetry, a column temperature of 40 °C with 0.1% (v/v) acidic water and acetonitrile as mobile phases, at a flow rate of 1 mL min−1 were determined to be the optimal analytical conditions. Calibration curves for orientin, isoorientin, vitexin, isovitexin, and rutin exhibited good linearity with correlation coefficients of 0.9999 over the 6.25−100.00 μg mL−1 range. Recovery values of 96.67−103.60% confirmed that the method was accurate for all flavonoids. The relative standard deviations of intra-day repeatability and inter-day reproducibility confirmed method preciseness, with values of less than 5.21% and 5.40%, respectively. The developed method was used to analyze flavonoids in CSE, with isomers satisfactorily separated and simultaneously quantified. We demonstrated that the developed HPLC method can be used to monitor flavonoids in buckwheat sprouts.

The monitoring of food quality and safety requires a suitable analytical method with simultaneous detection in order to control pesticide and herbicide residues. In this study, a novel analytical method, referred to as “dispersive solid−liquid extraction”, was applied to monitor seven sulfonylurea herbicides in strawberries. This method was optimized in terms of the amount of C18 and the volume of added water, and it was validated through satisfactory linearities (R2 > 0.99), recoveries of 70% to 84% with acceptable precisions, and limits of quantification lower than the maximum residue limits for the seven sulfonylurea herbicides in strawberries. The cleanup efficiency of the dispersive solid−liquid extraction technique was compared to that of the QuEChERS- (“quick, easy, cheap, effective, rugged and safe”) based method with dispersive solid phase extraction. The recoveries of the former were found to be comparable to those involving QuEChERS C18 cleanup (recoveries of 74%−87%). The method was used to determine sulfonylurea herbicide residues in ten strawberry samples. None of the samples had herbicide residues higher than that of limit of quantifications (LOQs) or maximum residue limits (MRLs). The results suggest that the dispersive solid−liquid extraction method combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) is effective for the analysis of sulfonylurea herbicide residues in strawberries.