Chemical characterization, multivariate analysis and comparison of biological activities of different parts of Fraxinus mandshurica.

Fraxinus mandshurica (Oleaceae) is used as a traditional medicinal plant for the treatment of red eyes, menstrual disorders, excessive leucorrhea, chronic bronchitis and psoriasis. To perform chemical characterization of the secondary metabolites of F. mandshurica roots, bark, stems and leaves, 32 samples were collected from eight provinces in this study. A total of 64 chemical components were detected from four different parts of F. mandshurica by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Meanwhile, a total of nine secoiridoids were obtained by natural product chemical extraction, isolation and identification methods. Quantitative analysis by high-performance liquid chromatography-diode array detection-mass spectrometry showed the highest total content of secoiridoids in the bark, which is also consistent with the traditional medicinal parts. The results of methodological validation showed that the correlation coefficient (R2) values were all >0.9993, indicating a good linear range of the standard curve, while the relative standard deviations of precision, reproducibility and stability were <3%, and the spiked recoveries ranged from 98.22 to 102.27%, indicating that the experimental method was reliable and stable. In addition, fingerprinting and a heatmap were established to demonstrate the content trends of F. mandshurica more visually from different origins. Multivariate analysis, including principal component analysis and partial least squares discriminant analysis, was performed to determine the chemical characteristics of different parts of F. mandshurica, and six characteristic secoiridoids that could be used to distinguish different origins were screened. Finally, the inhibition of tyrosinase, α-glucosidase, acetylcholinesterase and pancreatic lipase activities by the nine characteristic compounds and extracts from different parts were investigated, and the results showed that they all exhibited different degrees of enzyme activity inhibition and thus have potential applications in whitening and blemish removal, hypoglycemia, anti-Alzheimer's disease and anti-obesity as a new source of natural enzyme activity inhibitors. This study establishes an identification and evaluation method applicable to phytochemistry of different origins, which is a guideline for quality control, origin evaluation and clinical application of traditional medicinal plants. This is also an unprecedented study on the identification of the chemical composition of different parts of F. mandshurica, characteristic compounds and the inhibition of enzyme activity of extracts from different parts.

Hepatoprotective effect of dietary pterostilbene against high-fat-diet-induced lipid accumulation exacerbated by chronic jet lag via SIRT1 and SIRT3 activation.

Hepatic lipid metabolism is modulated by the circadian rhythm; therefore, circadian disruption may promote obesity and hepatic lipid accumulation. This study aims to investigate dietary pterostilbene (PSB) 's protective effect against high-fat-diet (HFD)-induced lipid accumulation exacerbated by chronic jet lag and the potential role of gut microbiota therein. Mice were treated with a HFD and chronic jet lag for 14 weeks. The experimental group was supplemented with 0.25% (w/w) PSB in its diet to evaluate whether PSB had a beneficial effect. Our study found that chronic jet lag exacerbates HFD-induced obesity and hepatic lipid accumulation, but these adverse effects were significantly mitigated by PSB supplementation. Specifically, PSB promoted hepatic lipolysis and ß-oxidation by upregulating SIRT1 expression, which indirectly reduced oxidative stress caused by lipid accumulation. Additionally, the PSB-induced elevation of SIRT1 and SIRT3 expression helped prevent excessive autophagy and mitochondrial fission by activating Nrf2-mediated antioxidant enzymes. The result was evidenced by the use of SIRT1 and SIRT3 inhibitors in in vitro studies, which demonstrated that activation of SIRT1 and SIRT3 by PSB is crucial for the translocation of PGC-1α and Nrf2, respectively. Moreover, the analysis of gut microbiota suggested that PSB's beneficial effects were partly due to its positive modulation of gut microbial composition and functionality. The findings of this study suggest the potential of dietary PSB as a candidate to improve hepatic lipid metabolism via several mechanisms. It may be developed as a treatment adjuvant in the future.

Modulating effects of capsaicin on glucose homeostasis and the underlying mechanism.

Abnormal glucose homeostasis is linked to a variety of metabolic syndromes, such as insulin resistance, obesity, type-2 diabetes mellitus, hypertension and cardiovascular diseases. Maintenance of normal glucose homeostasis is important for the body to keep normal biological functions. As the major bioactive ingredient in chili peppers responsible for the pungent flavor, capsaicin has been reported to effectively improve glucose homeostasis with low cytotoxicity. In this review, the modulating effects of capsaicin on glucose homeostasis in cell models, animal models and human trials are summarized through both TRPV1 dependent and TRPV1 independent pathways. The relevant molecular mechanisms underlying its regulatory effects are also evaluated. Understanding the effects and mechanisms of capsaicin on glucose metabolism could provide theoretical evidence for its application in the food and pharmaceutical industries.

Applications of multi-omics techniques to unravel the fermentation process and the flavor formation mechanism in fermented foods.

Fermented foods are important components of the human diet. There is increasing awareness of abundant nutritional and functional properties present in fermented foods that arise from the transformation of substrates by microbial communities. Thus, it is significant to unravel the microbial communities and mechanisms of characteristic flavor formation occurring during fermentation. There has been rapid development of high-throughput and other omics technologies, such as metaproteomics and metabolomics, and as a result, there is growing recognition of the importance of integrating these approaches. The successful applications of multi-omics approaches and bioinformatics analyses have provided a solid foundation for exploring the fermentation process. Compared with single-omics, multi-omics analyses more accurately delineate microbial and molecular features, thus they are more apt to reveal the mechanisms of fermentation. This review introduces fermented foods and an overview of single-omics technologies - including metagenomics, metatranscriptomics, metaproteomics, and metabolomics. We also discuss integrated multi-omics and bioinformatic analyses and their role in recent research progress related to fermented foods, as well as summarize the main potential pathways involved in certain fermented foods. In the future, multilayered analyses of multi-omics data should be conducted to enable better understanding of flavor formation mechanisms in fermented foods.

Investigating the Potential Anti-Alzheimer's Disease Mechanism of Marine Polyphenols: Insights from Network Pharmacology and Molecular Docking.

Marine polyphenols, including eckol(EK), dieckol(DK), and 8,8'-bieckol(BK), have attracted attention as bioactive ingredients for preventing Alzheimer's disease (AD). Since AD is a multifactorial disorder, the present study aims to provide an unbiased elucidation of unexplored targets of AD mechanisms and a systematic prediction of effective preventive combinations of marine polyphenols. Based on the omics data between each compound and AD, a protein-protein interaction (PPI) network was constructed to predict potential hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to provide further biological insights. In the PPI network of the top 10 hub genes, AKT1, SRC, EGFR, and ESR1 were common targets of EK and BK, whereas PTGS2 was a common target of DK and BK. GO and KEGG pathway analysis revealed that the overlapped genes between each compound and AD were mainly enriched in EGFR tyrosine kinase inhibitor resistance, the MAPK pathway, and the Rap1 and Ras pathways. Finally, docking validation showed stable binding between marine polyphenols and their top hub gene via the lowest binding energy and multiple interactions. The results expanded potential mechanisms and novel targets for AD, and also provided a system-level insight into the molecular targets of marine polyphenols against AD.

Bioactives from Crude Rice Bran Oils Extracted Using Green Technology.

Crude rice bran oils from different rice cultivars and extraction methods bear different contents of nutraceuticals. The health benefits of lowering cholesterol activity of rice bran oil being confirmed by many reports are partly attributed to non-nutrient nutraceuticals, especially γ-oryzanol, phytosterols, and policosanols. As the world has been facing the global warming crisis, green extraction technology is gaining attention from many sectors. The current study aims to compare the nutraceutical composition with respect to γ-oryzanol, phytosterol, and policosanol content as well as the antioxidant properties of crude rice bran oils extracted from white and red rice bran using three green technologies, comparing with conventional hexane extraction. The data show that the traditional solvent extraction gave the highest oil yield percentage (26%), but it was not significantly different from subcritical liquefied dimethyl ether extraction (24.6%). Subcritical liquefied dimethyl ether extraction gave higher oil yield than supercritical CO2 extraction (15.5-16.2%). The crude rice bran oil extracted using subcritical liquefied dimethyl ether extraction produced the highest total phenolic contents and antioxidant activities. The highest γ-oryzanol content of the crude rice bran oil was found in oil extracted by conventional cold press (1370.43 mg/100 g). The γ-oryzanol content of the oil obtained via subcritical liquefied dimethyl ether extraction was high (1213.64 mg/100 g) compared with supercritical CO2 extraction. The red rice bran yielded the crude rice bran oil with the highest total phytosterol content compared with the white bran, and the oil from red rice bran extracted with subcritical liquefied dimethyl ether generated the highest total phytosterol content (1784.17 mg/100 g). The highest policosanol content (274.40 mg/100 g) was also found in oil obtained via subcritical liquefied dimethyl ether extraction.

Comprehensive applications of metabolomics on tea science and technology: Opportunities, hurdles, and perspectives.

With the development of metabolomics analytical techniques, relevant studies have increased in recent decades. The procedures of metabolomics analysis mainly include sample preparation, data acquisition and pre-processing, multivariate statistical analysis, as well as maker compounds' identification. In the present review, we summarized the published articles of tea metabolomics regarding different analytical tools, such as mass spectrometry, nuclear magnetic resonance, ultraviolet-visible spectrometry, and Fourier transform infrared spectrometry. The metabolite variation of fresh tea leaves with different treatments, such as biotic/abiotic stress, horticultural measures, and nutritional supplies was reviewed. Furthermore, the changes of chemical composition of processed tea samples under different processing technologies were also profiled. Since the identification of critical or marker metabolites is a complicated task, we also discussed the procedure of metabolite identification to clarify the importance of omics data analysis. The present review provides a workflow diagram for tea metabolomics research and also the perspectives of related studies in the future.

Food polyphenols and Maillard reaction: regulation effect and chemical mechanism.

Maillard reaction is a non-enzymatic thermal reaction during food processing and storage. It massively contributes to the flavor, color, health benefits and safety of foods and could be briefly segmented into initial, intermediate and final stages with the development of a cascade of chemical reactions. During thermal reaction of food ingredients, sugar, protein and amino acids are usually the main substrates, and polyphenols co-existed in food could also participate in the Maillard reaction as a modulator. Polyphenols including flavan-3-ols, hydroxycinnamic acids, flavonoids, and tannins have shown various effects throughout the process of Maillard reaction, including conjugating amino acids/sugars, trapping α-dicarbonyls, capturing Amadori rearrangement products (ARPs), as well as decreasing acrylamide and 5-hydroxymethylfurfural (5-HMF) levels. These effects significantly influenced the flavor, taste and color of processed foods, and also decreased the hazard products' level. The chemical mechanism of polyphenols-Maillard products involved the scavenging of radicals, as well as nucleophilic addition and substitution reactions. In the present review, we concluded and discussed the interaction of polyphenols and Maillard reaction, and proposed some perspectives for future studies.

HighlightsFood polyphenols regulate Maillard reaction through substrates, initial, intermediate and final stages/products of Maillard reaction.The trapping ability of food polyphenols on α-dicarbonyls relied on the structural properties, and was also affected by reaction conditions such as pH value.Food polyphenols could act as potential inhibitors toward the formation of harmful compounds during advanced and final stages of Maillard reaction.The chemical mechanism of polyphenols-Maillard reaction products involved the scavenging of radicals, as well as nucleophilic addition and substitution.

Piperine Improves Lipid Dysregulation by Modulating Circadian Genes Bmal1 and Clock in HepG2 Cells.

Metabolic disorders are closely associated with the dysregulation of circadian rhythms. Many bioactive components with lipid metabolism-regulating effects have been reported to function through circadian clock-related mechanisms. As the main pungent principle of black pepper, piperine (PIP) has been demonstrated to possess anti-obesity bioactivity by affecting hepatic lipid metabolism-related factors. However, whether the circadian clock genes Bmal1 and Clock are involved in the protective effect of PIP against lipid metabolism disorders remains unknown. In this work, oleic acid (OA) induced lipid accumulation in HepG2 cells. The effect of PIP on redox status, mitochondrial functions, and circadian rhythms of core clock genes were evaluated. Results revealed that PIP alleviated circadian desynchrony, ROS overproduction, and mitochondrial dysfunction. A mechanism study showed that PIP could activate the SREBP-1c/PPARγ and AMPK/AKT-mTOR signaling pathways in a Bmal1/Clock-dependent manner in HepG2 cells. These results indicated that Bmal1 and Clock played important roles in the regulating effect of PIP on hepatic lipid homeostasis.

5-Demethylnobiletin Inhibits Cell Proliferation, Downregulates ID1 Expression, Modulates the NF-κB/TNF-α Pathway and Exerts Antileukemic Effects in AML Cells.

Acute myeloid leukemia (AML) is characterized by the dysregulation of hematopoietic cell proliferation, resulting in the accumulation of immature myeloid cells in bone marrow. 5-Demethylnobiletin (5-demethyl NOB), a citrus 5-hydroxylated polymethoxyflavone, has been reported to exhibit various bioactivities, such as antioxidant, anti-inflammatory and anticancer properties. In this study, we investigated the antileukemic effects of 5-demethyl NOB and its underlying molecular mechanisms in human AML cells. We found that 5-demethyl NOB (20−80 µM) significantly reduced human leukemia cell viability, and the following trend of effectiveness was observed: THP-1 ≈ U-937 > HEL > HL-60 > K562 cells. 5-Demethyl NOB (20 and 40 µM) modulated the cell cycle through the regulation of p21, cyclin E1 and cyclin A1 expression and induced S phase arrest. 5-Demethyl NOB also promoted leukemia cell apoptosis and differentiation. Microarray-based transcriptome, Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) of differentially expressed genes (DEGs) analysis showed that the expression of inhibitor of differentiation/DNA binding 1 (ID1), a gene associated with the GO biological process (BP) cell population proliferation (GO: 0008283), was most strongly suppressed by 5-demethyl NOB (40 µM) in THP-1 cells. We further demonstrated that 5-demethyl NOB-induced ID1 reduction was associated with the inhibition of leukemia cell growth. Moreover, DEGs involved in the hallmark gene set NF-κB/TNF-α signaling pathway were markedly enriched and downregulated by 5-demethyl NOB. Finally, we demonstrated that 5-demethyl NOB (20 and 40 µM), combined with cytarabine, synergistically reduced THP-1 and U-937 cell viability. Our current findings support that 5-demethyl NOB dramatically suppresses leukemia cell proliferation and may serve as a potential phytochemical for human AML chemotherapy.

Acetylation Enhances the Anticancer Activity and Oral Bioavailability of 5-Demethyltangeretin.

A kind of hydroxylated polymethoxyflavone (PMFs) existing in the citrus genus, 5-Demethyltangeretin (5-DTAN), has been reported to possess several bioactivities in vitro and in vivo. The aim of this study was to investigate whether acetylation could enhance the anticancer activity and oral bioavailability of 5-DTAN. PC-3 human prostate cancer cells were treated with tangeretin (TAN), 5-DTAN, and 5-acetylated TAN (5-ATAN), and the results showed that the cytotoxic effect 5-ATAN (IC50 value of 5.1 µM) on the cell viability of PC-3 cells was stronger than that of TAN (IC50 value of 17.2 µM) and 5-DTAN (IC50 value of 11.8 µM). Compared to 5-DTAN, 5-ATAN treatment caused a more pronounced DNA ladder, increased the sub-G1 phase population, and induced G2/M phase arrest in the cell cycle of PC-3 cells. We also found that 5-ATAN triggered the activation of caspase-3 and the progression of the intrinsic mitochondrial pathway in PC-3 cells, suggesting the induction of apoptosis. In a cell wound healing test, 5-ATAN dose-dependently reduced the cell migration, and the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) was decreased after 48 h of 5-ATAN treatment. Moreover, oral administration of 5-ATAN showed a significantly stronger inhibitory effect on tumor size and tumor weight in tumor-bearing nude mice than those of vehicle or the 5-DTAN group (p < 0.05). Furthermore, pharmacokinetic results showed that single-dose oral administration of 5-ATAN exhibited a higher maximum concentration (Cmax) and area under the curve (AUC) of 5-DTAN in plasma than that of 5-DTAN. More extensive distribution of 5-DTAN to most tissues of mice was also observed in mice treated with 5-ATAN for 7 days. In conclusion, acetylation strongly enhances the anticancer activity and oral bioavailability of 5-DTAN and could be a promising strategy to promote the potential bioactivities of natural products.

Bioactives of Momordica charantia as Potential Anti-Diabetic/Hypoglycemic Agents.

Momordica charantia L., a member of the Curcubitaceae family, has traditionally been used as herbal medicine and as a vegetable. Functional ingredients of M. charantia play important roles in body health and human nutrition, which can be used directly or indirectly in treating or preventing hyperglycemia-related chronic diseases in humans. The hypoglycemic effects of M. charantia have been known for years. In this paper, the research progress of M. charantia phytobioactives and their hypoglycemic effects and related mechanisms, especially relating to diabetes mellitus, has been reviewed. Moreover, the clinical application of M. charantia in treating diabetes mellitus is also discussed, hoping to broaden the application of M. charantia as functional food.

Nutraceutical Difference between Two Popular Thai Namwa Cultivars Used for Sun Dried Banana Products.

Musa (ABB group) "Kluai Namwa" bananas (Musa sp.) are widely grown throughout Thailand. Mali Ong is the most popular Kluai Namwa variety used as raw material for sun-dried banana production, especially in the Bangkratum District, Phitsanulok, Thailand. The sun-dried banana product made from Nanwa Mali Ong is well recognized as the best dried banana product of the country, with optimal taste compared to one made from other Kluai Namwa varieties. However, the production of Mali Ong has fluctuated substantially in recent years, leading to shortages. Consequently, farmers have turned to using other Kluai Namwa varieties including Nuanchan. This study investigated the nutraceutical contents of two popular Namwa varieties, Mali Ong and Nuanchan, at different ripening stages. Nutraceuticals in the dried banana products made from these two Kluai Namwa varieties and four commercial dried banana products were compared. Results indicated that the content of moisture, total sugar, and total soluble solids (TSS) (°Brix) increased, while total solids and texture values decreased during the ripening stage for both Kluai Namwa varieties. Rutin was the major flavonoid found in both Namwa Mali Ong and Nuanchan varieties ranging 136.00−204.89 mg/kg and 129.15−260.38 mg/kg, respectively. Rutin, naringenin, quercetin and catechin were abundant in both Namwa varieties. All flavonoids increased with ripening except for rutin, gallocatechin and gallocatechin gallate. There were no significant differences (p < 0.05) in flavonoid contents between both varieties. Tannic acid, ellagic acid, gallic acid, chlorogenic acid and ferulic acid were the main phenolic acids found in Mali Ong and Nuanchan varieties, ranging from 274.61−339.56 mg/kg and 293.13−372.66 mg/kg, respectively. Phenolic contents of both varieties decreased, increased and then decreased again during the development stage. Dopamine contents increased from 79.26 to 111.77 mg/kg and 60.38 to 125.07 mg/kg for Mali Ong and Nuanchan, respectively, but the amounts were not significantly different (p < 0.5) between the two Namwa varieties at each ripening stage. Inulin as fructooligosaccharide (FOS) increased with ripening steps. Production stages of sun-dried banana products showed no statistically significant differences (p < 0.05) between the two Namwa varieties. Therefore, when one variety is scarce, the other could be used as a replacement in terms of total flavonoids, phenolic acid, dopamine and FOS. In both Namwa varieties, sugar contents decreased after the drying process. Sugar contents of the dried products were 48.47 and 47.21 g/100 g. The drying process caused a reduction in total flavonoid contents and phenolic acid at 63−66% and 64−70%, respectively. No significant differences (p < 0.05) were found for total flavonoid and phenolic contents between the dried banana products made from the two Namwa varieties (178.21 vs. 182.53 mg/kg and 96.06 vs. 102.19 mg/kg, respectively). Products made from Nuanchan varieties (24.52 mg/kg) contained significantly higher dopamine than that from Mali Ong (38.52 mg/kg). The data also suggest that the banana maturity stage for production of the sun dried products was also optimum in terms of high nutraceutical level.

Flavor of tea (Camellia sinensis): A review on odorants and analytical techniques.

Tea is among the most consumed nonalcoholic beverages worldwide. Understanding tea flavor, in terms of both sensory aspects and chemical properties, is essential for manufacturers and consumers to maintain high quality of tea products and to correctly distinguish acceptable or unacceptable products. This article gives a comprehensive review on the aroma and off-flavor characteristics associated with 184 odorants. Although many efforts have been made toward the characterization of flavor compounds in different types of tea, modern flavor analytical techniques that affect the results of flavor analysis have not been compared and summarized systematically up to now. Thus, the overview mainly provides the instrumental flavor analytical techniques for both aroma and taste of tea (i.e., extraction and enrichment, qualitative, quantitative, and chemometric approaches) as well as descriptive sensory analytical methodologies for tea, which is helpful for tea flavor researchers. Flavor developments of tea evolved toward time-saving, portability, real-time monitoring, and visualization are also prospected to get a deeper insight into the influences of different processing techniques on the formation and changes of flavor compounds, especially desired flavor compounds and off-flavor substances present at (ultra)trace amounts in tea and tea products.

Biosynthetic pathways and metabolic engineering of spice flavors.

Historically, spices have played an important economic role, due to their large applications and unique flavor. The supply and cost of spice materials and their corresponding natural products are often affected by environmental, geopolitical and climatic conditions. Secondary metabolite composition, including certain flavor compounds in spice plants, is recognized and considered closely related to plant classification. Both genes and enzymes involved in the biosynthesis of spice flavors are constantly identified, which provides insight into metabolic engineering of flavor compounds (i.e. aroma and pungent compounds) from spice plants. In this review, a systematic meta-analysis was carried out based on a comprehensive literature survey of the flavor profiles of 36 spice plants from nine families. We also reviewed typical biosynthetic pathways and metabolic engineering of most representative aroma and pungent compounds that may assist in the future study of spice plants as biosynthetic factories facing a new challenge in creating spice products.

Dieckol Ameliorates Aß Production via PI3K/Akt/GSK-3ß Regulated APP Processing in SweAPP N2a Cell.

The proteolytic processing of amyloid precursor protein (APP) by ß-secretase (BACE1) and γ-secretase releases amyloid-ß peptide (Aß), which deposits in amyloid plaques and contributes to the initial causative events of Alzheimer's disease (AD). In the present study, the regulatory mechanism of APP processing of three phlorotannins was elucidated in Swedish mutant APP overexpressed N2a (SweAPP N2a) cells. Among the tested compounds, dieckol exhibited the highest inhibitory effect on both intra- and extracellular Aß accumulation. In addition, dieckol regulated the APP processing enzymes, such as α-secretase (ADAM10), ß-secretase, and γ-secretase, presenilin-1 (PS1), and their proteolytic products, sAPPα and sAPPß, implying that the compound acts on both the amyloidogenic and non-amyloidogenic pathways. In addition, dieckol increased the phosphorylation of protein kinase B (Akt) at Ser473 and GSK-3ß at Ser9, suggesting dieckol induced the activation of Akt, which phosphorylated GSK-3ß. The specific phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 triggered GSK-3ß activation and Aß expression. In addition, co-treatment with LY294002 noticeably blocked the effect of dieckol on Aß production, demonstrating that dieckol promoted the PI3K/Akt signaling pathway, which in turn inactivated GSK-3ß, resulting in the reduction in Aß levels.

CSC-3436 sensitizes triple negative breast cancer cells to TRAIL-induced apoptosis through ROS-mediated p38/CHOP/death receptor 5 signaling pathways.

Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) shows little or no toxicity in most normal cells and preferentially induces apoptosis in a variety of malignant cells. However, patients develop resistance to TRAIL, therefore, sensitizing agents that can sensitize the tumor cells to TRAIL-mediated apoptosis are necessary. In this study, we investigated the effect of 2-(3-hydroxyphenyl)-5-methylnaphthyridin-4-one (CSC-3436), an useful flavonoid, to overcome the TRAIL-resistant triple negative breast cancer (TNBC) cells. We found that CSC-3436 potentiated TRAIL-induced apoptosis in TRAIL-resistant TNBC cells and this correlated with the upregulation of death receptors (DR)-5 and down-regulation of decreased decoy receptor (DcR)-1 expression. When examined for its mechanism, we found that the decreased expression of anti-apoptotic proteins c-FLIPS/L, Bcl-Xl, Bcl-2, Survivin, and XIAP. CSC-3436 would increase the expression of Bax and promoted the cleavage of bid. In addition, the induction of DR5 by CSC-3436 was found to be dependent on the modulation of reactive oxygen species (ROS)/p38/C/EBP-homologous protein (CHOP) signaling pathways. Overall, our results indicated that CSC-3436 could potentiate the apoptotic effects of TRAIL through down-regulation of cell survival proteins and upregulation of DR5 via the ROS-mediated upregulation of CHOP protein.

Demethoxycurcumin induces apoptosis in HER2 overexpressing bladder cancer cells through degradation of HER2 and inhibiting the PI3K/Akt pathway.

Bladder cancer is the most common malignancy of the urinary tract and arising from the epithelial lining of the urinary bladder. Resistance to cytotoxic therapies is associated with overexpression of oncogenic proteins; including HER2, and Akt in chemotherapy resistance of bladder cancer. Various studies demonstrated that curcuminoids, the most important active phenolic compounds of turmeric (Curcuma longa), have anti-tumor activities in a wide range of human malignant cell lines. The aim of this study is to evaluate whether curcuminoids (curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin) could repress the expression of HER2 in HER2-overexpressing bladder cancer cells. Among the test compounds, DMC significantly suppressed the expression of HER2, and preferentially inhibited cell proliferation and induced apoptosis in HER2-overexpressing bladder cancer cells. DMC decreases HER2 level through inhibiting the interaction of HER2 and Hsp90. Our study also indicated that DMC showed additive activity in combination with chemotherapeutic agents, including paclitaxel and cisplatin. These findings show that DMC should be developed further as a new antitumor drug candidate for treatment of HER2-overexpressing bladder cancer.

Modulation of Brain-Derived Neurotrophic Factor (BDNF) Signaling Pathway by Culinary Sage (Salvia officinalis L.).

Culinary sage (Salvia officinalis L.) is a common spice plant in the mint family (Lamiaceae) well known for its distinctive culinary and traditional medicinal uses. Sage tea has been used traditionally as a brain-enhancing tonic and extracts from sage have been reported to have both cognitive and memory enhancing effects. Brain-derived neurotrophic factor (BDNF) is an endogenous signaling molecule involved in cognition and memory function. In this study, activity-guided fractionation employing preparative reverse-phase high performance liquid chromatography (RP-HPLC) of culinary sage extracts led to the discovery of benzyl 6-O-ß-D-apiofuranosyl-ß-D-glucoside (B6AG) as a natural product that upregulates transcription of neurotrophic factors in C6 glioma cells. Purified B6AG showed a moderate dose response, with upregulation of BDNF and with EC50 at 6.46 µM. To better understand the natural variation in culinary sage, B6AG was quantitated in the leaves of several commercial varieties by liquid chromatography-mass spectrometry (LC-MS). The level of B6AG in dried culinary sage was found to range from 334 ± 14 to 698 ± 65 µg/g. This study provided a foundation for future investigations, including quantitative inquiries on the distribution of B6AG within the different plant organs, explorations in optimizing post-harvest practices, and aid in the development of sage varieties with elevated levels of B6AG.

Key Aspects of Amadori Rearrangement Products as Future Food Additives.

Flavor is one of the most important factors in attracting consumers and maximizing food quality, and the Maillard reaction (MR) is highly-involved in flavor formation. However, Maillard reaction products have a big drawback in their relatively low stability in thermal treatment and storage. Amadori rearrangement products (ARPs), MR intermediates, can alternatively act as potential flavor additives for their better stability and fresh flavor formation ability. This review aims to elucidate key aspects of ARPs' future application as flavorings. The development of current analytical technologies enables the precise characterization of ARPs, while advanced preparation methods such as synthesis, separation and drying processes can increase the yield of ARPs to up to 95%. The stability of ARPs is influenced by their chemical nature, pH value, temperature, water activity and food matrix. ARPs are associated with umami and kokumi taste enhancing effects, and the flavor formation is related to amino acids/peptides of the ARPs. Peptide-ARPs can generate peptide-specific flavors, such as: 1,6-dimethy-2(1H)-pyrazinone, 1,5-dimethy-2(1H)-pyrazinone, and 1,5,6-trimethy-2(1H)-pyrazinone. However, further research on systematic stability and toxicology are needed.