Acetylated pelargonidin-3-O-glucoside alleviates hepatocyte lipid deposition through activating the AMPK-mediated lysosome-autophagy pathway and redox state.

Nonalcoholic fatty liver disease (NAFLD) is a worldwide public health issue, but a widely accepted therapy is still lacking until now. Anthocyanins are natural flavonoid compounds that possess various bioactivities, but their applications are limited due to their low bioavailability and stability. Acylated anthocyanins are reported to show higher stability, whereas their effects on NAFLD are still unclear. Herein, pelargonidin-3-O-(6''-acetyl)-glucoside (Ace Pg3G) was found to dose-dependently reduce intracellular lipid droplets and triglycerides, and improve cellular oxidative stress that accompanied lipid deposition. Besides, Ace Pg3G was proved to activate AMPK phosphorylation, thus stimulating AMPK-mediated lysosome-autophagy pathway to eliminate overloaded lipid. Further study unveiled that Ace Pg3G regulated genes related to lipid metabolism downstream of AMPK to inhibit lipid synthesis and accelerate lipid oxidation. Overall, this study provided the first evidence, to our best knowledge, that Ace Pg3G ameliorated free fatty acid-induced lipid deposition in hepatocytes through regulating AMPK-mediated autophagy pathways and redox state.

Carboxymethyl Chitosan-Coated Cyanidin-3-O-Glucoside-Beared Nanonutriosomes Suppress Palmitic Acid-Induced Hepatocytes Injury.

Cyanidin-3-O-glucoside (C3G) is classified as an anthocyanin (ACN) and is recognized for its remarkable antioxidant properties. Yet, the inadequate physicochemical stability of C3G restricts its potential for various biological applications. Thus, in this study, carboxymethyl chitosan (CMC)-coated nanonutriosomes (NS) were synthesized as a novel carrier for encapsulating C3G (CMC-C3G-NS) to improve C3G stability. CMC-C3G-NS exhibited a diameter of less than 200 nm along with an encouraging encapsulation efficiency exceeding 90%. Notably, the formulated CMC-C3G-NS possessed better stability under various pH, ionic, and oxygen conditions, improved controlled release properties, and higher hepatocellular uptake than uncoated particles (C3G-NS), indicating a longer retention time of C3G in a physiological environment. Of utmost significance, CMC-C3G-NS demonstrated superior alleviating effects against palmitic acid (PA)-induced oxidative hepatic damage compared to C3G-NS. Our study provided promising nanocarriers with the potential to deliver hydrophilic ACNs and controlled release properties for PA-induced hepatotoxicity alleviation.

Green synthesis of nanolipo-fibersomes using Nutriose® FB 06 for delphinidin-3-O-sambubioside delivery: Characterization, physicochemical properties, and application.

Anthocyanins are potential bioactive compounds with less bioavailability due to instability in physicochemical and physiological harsh environments. This study synthesized a "nanolipo-fibersomes (NLFS)" using Lipoid® S75 and Nutriose® FB 06 (dextrinization of wheat starch) through a self-assembly technique with probe sonication. We aimed to encapsulate delphinidin-3-O-sambubioside (D3S) successfully and evaluate physicochemical and controlled release properties with improved antioxidant activity on palmitic acid (PA)-induced colonic cells (Caco-2 cells). D3S-loaded nanolipo-fibersomes (D3S-NLFS) were nanosized (<150 nm), spherical shaped, and homogenously dispersed in solution with promising encapsulation efficiency (~ 89.31 to 97.31 %). Particles formation was further verified by FTIR. NLFS were well-stable in thermal, storage, and gastrointestinal mimic environments. NLFS exhibited better-controlled release and mucoadhesive properties compared to nanoliposomes (NL). The NLFS showed better cellular uptake than NL, which was correlated to higher mucoadhesive properties. Furthermore, D3S-NLFS exhibited promising protective effects against PA-induced cytotoxicity, O2•- radicals generation, mitochondrial dysfunctions, and GSH depletion, while the free D3S was ineffective. Among D3S-loaded nanoparticles, D3S-NLFS 3 was the most efficient nanocarrier followed by D3S-NLFS 2, D3S-NLFS 1, and D3S-NL, respectively. The above data suggest that nanolipo-fibersomes can be considered as promising nanovesicles for improving colonic delivery of hydrophilic compounds with controlled release properties and greater antioxidant activity.

Differential expression profiles and functional analysis of long non-coding RNAs in calcific aortic valve disease.

AIM: To evaluate the expression profile of long non-coding RNAs (lncRNAs) in calcific aortic valve disease (CAVD) and explore their potential mechanism of action. METHODS: The gene expression profiles (GSE153555, GSE148219, GSE199718) were downloaded from the Gene Expression Omnibus (GEO) database and FastQC was run for quality control checks. After filtering and classifying candidate lncRNAs by differentially expressed genes (DEGs) and weighted co-expression networks (WGCNA) in GSE153555, we predicted the potential cis- or trans-regulatory target genes of differentially expressed lncRNAs (DELs) by using FEELnc and established the competitive endogenous RNA (ceRNA) network by miRanda, more over functional enrichment was analyzed using the ClusterProfiler package in R Bioconductor. The hub cis- or trans-regulatory genes were verified in GSE148219 and GSE199718 respectively. RESULTS: There were 340 up-regulated lncRNAs identified in AS group compared with the control group (|log2Fold Change| ≥ 1.0 and Padj ≤ 0.05), and 460 down-regulated lncRNAs. Based on target gene prediction and co-expression network construction, twelve Long non-coding RNAs (CDKN2B-AS1, AC244453.2, APCDD1L-DT, SLC12A5-AS1, TGFB3, AC243829.4, MIR4435-2HG, FAM225A, BHLHE40-AS1, LINC01614, AL356417.2, LINC01150) were identified as the hub cis- or trans-regulatory genes in the pathogenesis of CAVD which were validated in GSE148219 and GSE19971. Additionally, we found that MIR4435-2HG was the top hub trans-acting lncRNA which also plays a crucial role by ceRNA pattern. CONCLUSION: LncRNAs may play an important role in CAVD and may provide a new perspective on the pathogenesis, diagnosis, and treatment of this disease. Further studies are required to illuminate the underlying mechanisms and provide potential therapeutic targets.

Identification of a novel α-glucosidase inhibitor from Melastoma dodecandrum Lour. fruits and its effect on regulating postprandial blood glucose.

Melastoma dodecandrum Lour. (MDL) extracts have shown potent α-glucosidase inhibitory activity, suggesting MDL might be a good source of α-glucosidase inhibitors. The aim of the study was to identify compounds in MDL extracts with α-glucosidase inhibitory activities and evaluate their effect on postprandial blood glucose as well as elucidating the underlying mechanisms of inhibition. A total of 34 polyphenols were identified in MDL fruits, among which 10 anthocyanins and three proanthocyanidin derivatives were discovered for the first time. Dosing mice with MDL extracts (100 mg/kg body weight, by gavage) was associated with a significantly decrease in postprandial blood glucose concentrations after oral administration of maltose. The most potent α-glucosidase inhibitor was identified as casuarictin (IC50 of 0.21 µg/mL). Casuarictin bound competitively to α-glucosidase, occupying not only the catalytic site but also forming strong hydrogen bonds with α-glucosidase residues. Therefore, casuarictin derived from MDL fruits might be used as novel α-glucosidase inhibitor in functional foods or other dietary products.

Potential micro-/nano-encapsulation systems for improving stability and bioavailability of anthocyanins: An updated review.

Anthocyanins (ACNs) are notable hydrophilic compounds that belong to the flavonoid family, which are available in plants. They have excellent antioxidants, anti-obesity, anti-diabetic, anti-inflammatory, anticancer activity, and so on. Furthermore, ACNs can be used as a natural dye in the food industry (food colorant). On the other hand, the stability of ACNs can be affected by processing and storage conditions, for example, pH, temperature, light, oxygen, enzymes, and so on. These factors further reduce the bioavailability (BA) and biological efficacy of ACNs, as well as limit ACNs application in both food and pharmaceutics field. The stability and BA of ACNs can be improved via loading them in encapsulation systems including nanoemulsions, liposomes, niosomes, biopolymer-based nanoparticles, nanogel, complex coacervates, and tocosomes. Among all systems, biopolymer-based nanoparticles, nanohydrogels, and complex coacervates are comparatively suitable for improving the stability and BA of ACNs. These three systems have excellent functional properties such as high encapsulation efficiency and well-stable against unfavorable conditions. Furthermore, these carrier systems can be used for coating of other encapsulation systems (such as liposome). Additionally, tocosomes are a new system that can be used for encapsulating ACNs. ACNs-loaded encapsulation systems can improve the stability and BA of ACNs. However, further studies regarding stability, BA, and in vivo work of ACNs-loaded micro/nano-encapsulation systems could shed a light to evaluate the therapeutic efficacy including physicochemical stability, target mechanisms, cellular internalization, and release kinetics.

Geniposide Alleviates Oxidative Damage in Hepatocytes through Regulating miR-27b-3p/Nrf2 Axis.

Geniposide (GEN), a main compound extracted from Gardenia jasminoides fruit, has various biological activities including anti-inflammation, cellular damage alleviation, neuroprotection, and others. However, the effect of GEN on oxidative stress in hepatic cells is yet to be investigated. Our study uncovered that GEN eliminated excess intracellular free radicals by activating the Nrf2/ARE signaling pathway in H2O2-treated hepatocytes, while the protective effect was blocked by ML385 (an inhibitor of Nrf2). Moreover, H2O2 led to upregulation of miR-27b-3p in L02 cells, which was restrained by GEN. Overexpression of miR-27b-3p greatly weakened the antioxidant capacity of GEN in hepatocytes via directly targeting the Nrf2 gene. Our findings indicated that GEN treatment recovered H2O2-induced oxidative stress via targeting miR-27b-3p and thereby enhanced the antioxidant capacity by stimulating nuclear translocation and accumulation of Nrf2. These findings suggest that inhibition of miR-27b-3p to activate the Nrf2/ARE pathway by GEN is a potential alternative for hepatic oxidative damage alleviation.

Improvement of stability and lipophilicity of pelargonidin-3-glucoside by enzymatic acylation with aliphatic dicarboxylic acid.

Dicarboxylic acids derived acylated-anthocyanins are common in nature, which can also be obtained by enzymatic acylation of anthocyanins. However, little research have focused on the properties of anthocyanins with dicarboxylic acid derivatives due to the complexity of isolation, detection, and identification. In this work, pelargonidin-3-glucoside (Pg3G) was acylated with various dicarboxylic acids. The conversion yields of acylated Pg3G were positively associated with carbon chain lengths of dicarboxylic acids. The primary acylated products were identified as pelargonidin-3-(6″-malonyl) glucoside, pelargonidin-3-(6″-succinyl) glucoside, and pelargonidin-3-(6″-glutaryl) glucoside using LC-MS and NMR. Furthermore, the three acylated Pg3G derivatives exhibited improved thermostability and enhanced lipophilicity compared with Pg3G. The improved thermostability was attributed to the influence of dicarboxylic acids substituent on the distribution of flavylium cation, quinoidal base, hemiketal, cis-chalcone, and trans-chalcone at the equilibrium condition. Overall, our research provided insights about the improved stability and lipophilicity of pelargonidin-3-glucoside following enzymatic acylation with aliphatic dicarboxylic acids.

Development of a prognostic nomogram based on an eight-gene signature for esophageal squamous cell carcinoma by weighted gene co-expression network analysis (WGCNA).

Background: Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignant tumor. This study aims to develop a robust prognostic model for ESCC. Methods: Expression profiles of ESCC were downloaded from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Co-expressed modules were constructed by weighted gene co-expression network analysis (WGCNA). Differentially expressed genes (DEGs) between ESCC and normal samples were identified with the screening criteria of adjusted P value <0.05 and log |fold change (FC)| >1. After univariate and multivariate Cox regression analysis, an 8-gene module was constructed. A receiver operating characteristic (ROC) curve for overall survival (OS) was used to assess the prediction efficacy of the risk score. A nomogram was developed based on the risk score, age, gender, and stage for 1-, 2- and 3-year survival. The potential biological functions and pathways of the 8 genes were predicted using the Metascape database. Results: The 2 ESCC-related co-expression modules were built via WGCNA. Among all DEGs, 55 survival-related genes were identified for ESCC. Based on these genes, an 8-gene module was constructed, composed of CFAP53, FCGR2A, FCGR3A, GNGT1, IGF2, LINC01524, MAGEA3, and MAGEA6. The area under the curve (AUC) was 0.961, suggesting that the risk score could effectively predict the OS of patients with ESCC. Furthermore, the nomogram exhibited high accuracy in predicting the survival rate of ESCC patients at 1, 2, and 3 years. These genes were mainly involved in ESCC-related pathways such as extracellular matrix organization, collagen formation, and blood vessel development. Conclusions: Our nomogram based on the 8-gene risk score could be a reliable prognostic tool for ESCC.

Acetylated pelargonidin-3-O-glucoside exhibits promising thermostability, lipophilicity, and protectivity against oxidative damage by activating the Nrf2/ARE pathway.

Anthocyanins are natural products that display diverse bioactivities but are limited in their applications by low stability and bioavailability. Acylated anthocyanins are found to possess higher stability, while their bioactivities are still obscure. In this study, acetylation of pelargonidin-3-O-glucoside (Pg3G) was catalyzed by Candida antarctica lipase B (CALB) for the first time, with a conversion rate up to 88.77% over 48 h. The acetylated product was identified as pelargonidin-3-O-(6''-acetyl)-glucoside and its properties were detected. Notably, acetylated Pg3G (Ace Pg3G) possessed better thermostability and lipophilicity than Pg3G, indicating a longer retention time at physiological pH and facilitating penetration into the lipophilic medium as well as the cell membrane. Most importantly, Ace Pg3G exerted better alleviation effects against H2O2-induced oxidative hepatic damage than parent Pg3G via activating the Nrf2/ARE signaling pathway and upregulating the expressions of the downstream phase II detoxification enzymes GCLC and HO-1, thereby reversing redox imbalance and enhancing cell survival. Overall, our research unveiled the better health benefits of Ace Pg3G and also provided new insights about the applications of acetylated anthocyanins in food, cosmetic, and pharmaceutical products.

The role of the Hippo pathway in heart disease.

Heart disease, including coronary artery disease, myocardial infarction, heart failure, cardiac hypertrophy, and cardiomyopathies, is the leading causes of death worldwide. The Hippo pathway is a central controller for organ size and tissue growth, which plays a pivotal role in determining cardiomyocytes and nonmyocytes proliferation, regeneration, differentiation, and apoptosis. In this review, we summarize the effects of the Hippo pathway on heart disease and propose potential intervention targets. Especially, we discuss the molecular mechanisms of the Hippo pathway involved in maintaining cardiac homeostasis by regulating cardiomyocytes and nonmyocytes function in the heart. Based on this, we conclude that the Hippo pathway is a promising therapeutic target for cardiovascular therapy, which will bring new perspectives for their treatments.

Bioavailability, Absorption, and Metabolism of Pelargonidin-Based Anthocyanins Using Sprague-Dawley Rats and Caco-2 Cell Monolayers.

The present study is aimed to clarify the absorption and metabolism properties of pelargonidin-based anthocyanins. Results showed that pelargonidin-3-O-rutinoside (Pg3R) was absorbed in its intact form after oral administration and reached a maximum plasma concentration of 175.38 ± 55.95 nM at 60 min. Three main metabolites were identified in plasma, including Pg3R-monoglucuronide (m/z 755.2046), Pg3R-hydroxylated (m/z 595.1644), and Pg3R-demethylated (m/z 565.1569) metabolites. The plasma concentration of the Pg3R-demethylated metabolite (57.04 ± 23.15 nM) was much higher than that of other two metabolites, indicating that demethylation was the main metabolic pathway for Pg3R, while the glucuronide conjugate was detected as the dominant metabolic form of pelargonidin-3-O-glucoside (Pg3G). The bioavailability of Pg3R (1.13%) was fourfold higher than that of Pg3G (0.28%), demonstrating that anthocyanins linked to the rutinoside may exhibit higher bioavailability than that of glucoside. In vitro transport study unveiled that passive diffusion and active efflux were involved in the absorption of Pg3R and Pg3G.

Malvidin-3-O-Glucoside from Blueberry Ameliorates Nonalcoholic Fatty Liver Disease by Regulating Transcription Factor EB-Mediated Lysosomal Function and Activating the Nrf2/ARE Signaling Pathway.

Nonalcoholic fatty liver disease (NAFLD) has become a universal health issue, whereas there is still a lack of widely accepted therapy until now. Clinical research studies have shown that blueberry could effectively regulate the lipid metabolism, thereby improving obesity-related metabolic syndromes; however, the specific active substances and mechanisms remain unclear. Herein, the effects of the major 10 kinds of anthocyanins from blueberry against NAFLD were investigated using an free fatty acid (FFA)-induced cell model. Among these anthocyanins, malvidin-3-O-glucoside (M3G) and malvidin-3-O-galactoside (M3Ga) could remarkably ameliorate FFA-induced lipid accumulation. Besides, M3G and M3Ga also inhibited oxidative stress via suppressing reactive oxygen species and superoxide anion overproduction, increasing glutathione levels, and enhancing activities of antioxidant enzymes. Further studies unveiled that the representative anthocyanin M3G-upregulated transcription factor EB (TFEB)-mediated lysosomal function possibly interacted with TFEB and activated the Nrf2/ARE (antioxidant responsive element) signaling pathway. Overall, this study enriched the knowledge about the health-promoting effects of blueberry anthocyanins against NAFLD and provided ideas for the development of functional foods of blueberry anthocyanins.

Improving the physicochemical stability and functionality of nanoliposome using green polymer for the delivery of pelargonidin-3-O-glucoside.

This study aimed to improve the physicochemical stability of nanoliposome (NL) with enhanced functionality for the delivery of Pelargonidin-3-O-glucoside (P3G) using biopolymers, i.e. chitosan (CH) and pectin (P). In this study, we successfully developed stabilized liposomal carriers, i.e. CH-conjugated NL (CH-NL) and P-conjugated CH-NL (P-CH-NL) using an optimum concentration of CH (0.6 wt%) and P (0.5 wt%). Results revealed that P-CH-NL had better physical stability to salt and pH with maximum P3G retention (>97%) under oxidative, thermal, and UV conditions. Nanoliposomes were more stable under refrigerated-storage and ensured high P3G retention (>96%). In vitro mucoadhesion study revealed that CH-NL had better mucin adsorption efficiency (59.72%) followed by P-CH-NL and NL. Furthermore, CH-NL and P-CH-NL alternatively had better stability to serum than NL. Taken together, the stabilization of nanoliposome using chitosan and pectin can be a promising approach for the delivery of hydrophilic compounds in association with enhanced stability and functionality.

Malvidin-3-O-arabinoside ameliorates ethyl carbamate-induced oxidative damage by stimulating AMPK-mediated autophagy.

Ethyl carbamate (EC) is an environmental toxin, commonly present in various fermented foods and beverages, as well as tobacco and polluted ambient air. However, studies on the effects of EC-induced toxicity on the intestines and potential protection methods are limited. In this study, we show that EC could cause severe toxicity in intestinal epithelial cells (IECs) triggering the induction of decreased cell viability, ROS accumulation and glutathione (GSH) depletion in a dose-dependent manner. Based on these results, we established an EC-treated IEC model to screen the potential protective effects of 12 kinds of anthocyanins extracted from blueberry. Interestingly, we found that malvidin-3-O-arabinoside (M3A) significantly reversed the oxidative damage caused by EC exposure by stimulating autophagy flux, which was determined by the LC3-II level and GFP-RFP-LC3 transfection experiment. Enhancement of autophagy was mainly ascribed to the regulation of lysosomes. M3A pretreatment remarkably upregulated LAMP-1 expression, which indicated elevated lysosomal mass. Besides, M3A also successfully restored lysosomal acidity and subsequently strengthened lysosomal functions. Furthermore, M3A stimulated phosphorylation of AMP-activated protein kinase (AMPK), a master regulator of autophagy. Furthermore, our study indicated the possibility of EC-caused oxidative damage to the intestines and unveiled the remarkably protective benefits of M3A-induced AMPK-mediated autophagy against this toxicity.

Discovery of anthocyanins from cranberry extract as pancreatic lipase inhibitors using a combined approach of ultrafiltration, molecular simulation and spectroscopy.

Obesity is a chronic disease that has been causing serious problems all over the world. However, there is a lack of available therapeutic approaches to treat obesity. The FDA-approved drug orlistat has severe side effects, such as abdominal pain, flatulence and oily stool. As the therapeutic target of orlistat is pancreatic lipase, there is an urgent need for discovery of new pancreatic lipase inhibitors from natural sources that have reduced side effects compared with orlistat. In this study, ultrafiltration in combination with molecular simulation and spectroscopy was reported as an effective approach for identifying new pancreatic lipase inhibitors from anthocyanin-rich berry sources. Using this approach, four monomeric anthocyanins cyanidin-3-O-arabinoside (C3A), cyanidin-3-O-galactoside (C3Ga), peonidin-3-O-arabinoside (Pn3A) and peonidin-3-O-galactoside (Pn3Ga) from cranberries were discovered as potent pancreatic lipase inhibitors. These four cranberry anthocyanins were shown to form hydrophobic interactions and hydrogen bonds with pocket amino acid residues in molecular docking and molecular dynamics simulations. C3A showed greater impact on secondary structures of the enzyme and showed higher binding capacity with the enzyme compared with C3Ga, Pn3A and Pn3Ga as observed by CD and fluorescence spectroscopy. The structure-activity relationships were then investigated and summarized as both the structures of the B ring and glycosyl group were related to the inhibitory activities of anthocyanins. In short, our results suggested that cranberry anthocyanins could be developed as food supplements to facilitate the prevention and treatment of obesity.

Andrographolide Exerts Antihyperglycemic Effect through Strengthening Intestinal Barrier Function and Increasing Microbial Composition of Akkermansia muciniphila.

Accumulating evidence indicates that type 2 diabetes (T2D) is associated with intestinal barrier dysfunction and dysbiosis, implying the potential targets for T2D therapeutics. Andrographolide was reported to have several beneficial effects on diabetes and its associated complications. However, the protective role of andrographolide, as well as its underlying mechanism against T2D, remains elusive. Herein, we reported that andrographolide enhanced intestinal barrier integrity in LPS-induced Caco-2 cells as indicated by the improvement of cell monolayer barrier permeability and upregulation of tight junction protein expression. In addition, andrographolide alleviated LPS-induced oxidative stress by preventing ROS and superoxide anion radical overproduction and reversing glutathione depletion. In line with the in vitro results, andrographolide reduced metabolic endotoxemia and strengthened gut barrier integrity in db/db diabetic mice. We also found that andrographolide appeared to ameliorate glucose intolerance and insulin resistance and attenuated diabetes-associated redox disturbance and inflammation. Furthermore, our results indicated that andrographolide modified gut microbiota composition as indicated by elevated Bacteroidetes/Firmicutes ratio, enriched microbial species of Akkermansia muciniphila, and increased SCFAs level. Taken together, this study demonstrated that andrographolide exerted a glucose-lowering effect through strengthening intestinal barrier function and increasing the microbial species of A. muciniphila, which illuminates a plausible approach to prevent T2D by regulating gut barrier integrity and shaping intestinal microbiota composition.

Colonic delivery of pelargonidin-3-O-glucoside using pectin-chitosan-nanoliposome: Transport mechanism and bioactivity retention.

Colon-targeted delivery is an active area of research as it can improve drug stability, bioactivity, and lessen the systematic toxicity. In this study, the colon-specific delivery of pelargonidin-3-O-glucoside (P3G) was investigated using pectin (P)/chitosan (CH)-functionalized nanoliposome (NL). The food simulant stability, transport mechanism, and bioactivity retention potential of carrier systems were studied. Results showed that polymer-coated nanoliposomes (P-CH-NL and CH-NL) improved the thermal and food simulant stability as well as enhanced the P3G retention during the in vitro digestion. The maximum P3G retention after enzymatic and non-enzymatic digestion was observed by P-CH-NL and the values were 47.5% and 57.5%, respectively. However, all nanoliposomal carriers followed Fickian diffusion mechanism both in in vitro food simulants and in vitro digestion models. Digested functionalized nanoliposomes revealed higher antioxidant properties after gastric digestion. Following by simulated intestinal fluid digestion, ABTS antioxidant activity of P-CH-P3G-NL was 12.52% and 6.31% higher than that of P3G-NL and CH-P3G-NL, respectively, while DPPH scavenging capacity of P-CH-P3G-NL was 5.57% and 1.86% greater than that of P3G-NL and CH-P3G-NL, respectively. Therefore, the developed functionalized nanoliposome can be useful for colon-targeted delivery and applicable in functional foods and/or beverages.

Structure-based design of human pancreatic amylase inhibitors from the natural anthocyanin database for type 2 diabetes.

Human Pancreatic Amylase (HPA) is an important target for prevention and treatment of type 2 diabetes. Acarbose is a currently available drug acting as a HPA inhibitor, but its gastrointestinal side-effects cannot be neglected. Thus, developing novel HPA inhibitors with no side-effects is of great importance. Herein, we adopted a structure-based design approach and discovered a potent HPA inhibitor, malvidin 3-O-arabinoside (M3A), from the natural anthocyanin database. We identified M3A as an effective HPA inhibitor through virtual screening, enzyme activity and enzyme kinetic assays. We reported the structure and activity relationships as both the anthocyanidin core and glucosyl group affected the HPA inhibitory effect of anthocyanins. Molecular dynamics studies indicated that the HPA inhibition of M3A occurred via its binding to the HPA key catalytic residues Arg195 and Asp197 through stable hydrogen bonding. In addition, M3A was found to reduce α-helix fractions and increase ß-sheet fractions in CD spectrometry. Further in vivo studies showed that M3A significantly ameliorated the postprandial blood glucose level. Taken together, our results provide new insights into the development of novel HPA inhibitors from natural sources as food supplements for type 2 diabetes.

Variations of PCDD/Fs emissions from secondary nonferrous smelting plants and towards to their source emission reduction.

Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) are cancerogenic organic pollutants that priority controlled by Stockholm Convention with globally 183 signatories now. Secondary nonferrous smelting plants are confirmed to be important sources in China due to its large industrial activities and high emissions of PCDD/Fs. It is important to prioritize source to achieve source emission reduction by conducting field monitoring on typical case plants. Here, the emission profiles and levels of PCDD/Fs were investigated in 25 stack gas samples collected from three secondary copper production (SeCu), two secondary zinc production (SeZn) and two secondary lead production (SePb). Both average mass concentration and toxic equivalency quantity (TEQ) concentrations of PCDD/Fs all generally decreased in the order: SeCu > SeZn > SePb. It is noteworthy that the mean TEQ concentration in stack gas from SeCu with oxygen-enrich melting furnace technology, at 2.7 ng I-TEQ/Nm3, was much higher than the concentrations of other smelting processes. The average emission factors and annual release amounts of PCDD/Fs from SeCu, SePb and SeZn investigated were 28.4, 1.5, 10.4 µg I-TEQ/t and 1.03, 0.023, 0.17 g I-TEQ/year, respectively. The ratios of 2,3,7,8-TCDF to 1,2,3,7,8-PeCDF and OCDD to 1,2,3,7,8,9-HxCDD varied to large extent for three metal smelting, which could be used as diagnostic ratios of tracing specific PCDD/Fs sources. Addition of copper-containing sludge into the raw materials might lead to higher PCDD/Fs emissions. It is important to emphasize and reduce the PCDD/Fs emissions from oxygen-enrich melting furnace from secondary copper productions.