Trilobatin regulates glucose metabolism by ameliorating oxidative stress and insulin resistance in vivo and in vitro.

OBJECTIVES: Trilobatin, a glycosylated dihydrochalcone, has been reported to have anti-diabetic properties. However, the underlying mechanism remains unexplained. METHODS: In this investigation, the regulation of trilobatin on glucose metabolism of insulin resistance (IR)-HepG2 cells and streptozocin (STZ)-induced mice and its mechanism were evaluated. KEY FINDINGS: Different doses of trilobatin (5, 10 and 20 µM) increased glucose consumption, glycogen content, hexokinase (HK), and pyruvate kinase (PK) activity in IR-HepG2 cells. Among them, the HK and PK activity in IR-HepG2 cells treated with 20 µM trilobatin were 1.84 and 2.05 times than those of the IR-group. The overeating, body and tissue weight, insulin levels, liver damage, and lipid accumulation of STZ-induced mice were improved after feeding with different doses of trilobatin (10, 50, and 100 mg/kg/d) for 4 weeks. Compared with STZ-induced mice, fasting blood glucose decreased by 61.11% and fasting insulin (FINS) increased by 48.6% after feeding trilobatin (100 mg/kg/d). Meanwhile, data from quantitative real-time polymerase chain reaction (qRT-PCR) revealed trilobatin ameliorated glycogen synthesis via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3ß (GSK-3ß) signaling pathway in IR-HepG2 cells and in STZ-induced mice. Furthermore, in vitro and in vivo experiments showed that trilobatin ameliorated oxidative stress by regulating the mRNA expression of nuclear erythroid-2 related factor 2 (Nrf2)/kelch-like ECH associated protein-1 (Keap-1) pathway as well as heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO-1). CONCLUSIONS: Our research reveals a novel pharmacological activity of trilobatin: regulating glucose metabolism through PI3K/Akt/GSK-3ß and Nrf2/Keap-1 signaling pathways, improving insulin resistance and reducing oxidative stress. Trilobatin can be used as a reliable drug resource for the treatment of glucose metabolism disorders.

Inhibitory mechanism of chrysin and diosmetin to α-glucosidase: insights from kinetics, multispectroscopy and molecular docking investigations.

Inhibition of α-glucosidase activity is a promising method to prevent postprandial hyperglycemia. The inhibitory effect and interaction of chrysin and diosmetin on α-glucosidase were studied in this study. The results of inhibition kinetics showed that chrysin and diosmetin reversibly inhibited α-glucosidase activity with IC50 value of 26.445 ± 1.406 µmol L-1 and 18.380 ± 1.264 µmol L-1, respectively. Further research revealed that chrysin exhibited a mixed-type inhibitory pattern against α-glucosidase, while diosmetin was noncompetitive inhibitory with Ki value of (2.6 ± 0.04) ×10-4 mol L-1. Fluorescence spectroscopy showed that both chrysin and diosmetin could quench the intrinsic fluorescence of α-glucosidase, the maximum emission wavelength of tyrosine (Tyr) and tryptophan (Trp) were not moved by chrysin, but red shifted by diosmetin. UV-Vis, fourier transform infrared spectroscopy (FT-IR) and circular dichroism (CD) measurements showed that the secondary structure and microenvironment of α-glucosidase were changed by chrysin and diosmetin. Further analysis of molecular docking showed that chrysin and diosmetin could bind with α-glucosidase and might cause the decrease of α-glucosidase activity. The results of molecular dynamics (MD) simulation showed that the stability of chrysin (or diosmetin)-α-glucosidase complex system was changed during binding process. In conclusion, chrysin and diosmetin are good α-glucosidase inhibitors.Communicated by Ramaswamy H. Sarma.

Inhibition of α-glucosidase by trilobatin and its mechanism: kinetics, interaction mechanism and molecular docking.

α-Glucosidase is related to the increase in postprandial blood glucose in vivo. Inhibition of α-glucosidase is supposed to be an effective approach to treat type 2 diabetes mellitus (T2DM). Trilobatin, a member of the dihydrochalcone family, shows anti-oxidant, anti-inflammatory and anti-diabetic activities. In this study, the inhibitory activity and mechanism of trilobatin on α-glucosidase were investigated using multispectroscopic and molecular docking techniques. The kinetic analysis showed that trilobatin reversibly inhibited α-glucosidase in a noncompetitive-type manner and the value of IC50 was 0.24 ± 0.02 mM. The analysis of fluorescence spectra demonstrated that the formation of the trilobatin-α-glucosidase complex was driven mainly by hydrogen bonding and van der Waals forces, resulting in the conformational changes of α-glucosidase. Fourier transform infrared spectroscopy (FT-IR) and circular dichroism (CD) measurements suggested that the interaction could change the micro-environment and conformation of α-glucosidase affected by trilobatin. Molecular docking analysis determined the exact binding sites of trilobatin on α-glucosidase. These results indicated that trilobatin is a strong α-glucosidase inhibitor, thus it could be conducive to ameliorate T2DM.

Antioxidant and functional properties of cowhide collagen peptides.

In the present study, antioxidant activities and functional properties of cowhide collagen antioxidant peptides (CCAPs) with different molecular weight (MW) were investigated. The optimum preparation conditions of CCAPs were hydrolysis time of 1.53 hr, temperature of 54.9 °C, pH 7.38, and neutral enzyme to trypsin ratio of 0.048 g: 0.016 g according to single factor test and response surface methodology (RSM). Three fractions (CCAP-I, CCAP-II, and CCAP-III) were obtained by ultrafiltration and lyophilization. Antioxidant activities revealed that CCAP-III had high reducing power activity (0.323 ± 0.035) and scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals (64.30 ± 5.99%), 2,2-azino-bis-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) radicals (75.25 ± 3.14%), and hydroxyl radicals (68.26 ± 6.74%) compared to the other fractions. In addition, LC-MS/MS analysis showed that Ala-Gly-Glu-Arg, Gly-Ile-Ala-Gly-Glu-Arg, Gly-Pro-Ala-Gly-Pro-Ala-Gly-Pro-Arg, Gly-Val-Val-Gly-Pro-Glu-Gly-Ala-Arg and Gly-Phe-Ser-Gly-Leu-Asp-Gly-Ala-Lys were the major peptides of CCAP-III. CCAP-III showed good hygroscopicity (HYG), water holding capacity (WHC), and oil holding capacity (OHC) when compared with CCAP-I and CCAP-II. However, CCAP-II has great emulsifying properties, and CCAP-I has excellent foaming properties. Therefore, CCAPs can be used as a promising source of functional peptides with antioxidant properties. PRACTICAL APPLICATION: This study demonstrated the peptides of cowhide collagen has superior antioxidant and functional properties. This study provided a scientific basis for the preparation of antioxidant peptides from cowhide collagen.

Hyaluronic acid coating on the surface of curcumin-loaded ZIF-8 nanoparticles for improved breast cancer therapy: An in vitro and in vivo study.

Despite developments in surgery and chemotherapy, effective treatment of breast cancer is still an urgent problem owing to recurrence and metastasis. By combining the advantages of curcumin (Cur), zeolitic imidazolate framework-8 nanoparticles (ZIF-8), and hyaluronic acid (HA) in breast cancer therapy, Cur-loaded and HA-coated ZIF-8 (Cur@ZIF-8@HA) were synthesized using a method based on the pH-dependent solubility of Cur and the electrostatic interactions between zinc ions and carboxyl groups of HA. Cur@ZIF-8 were also prepared as a control group. Comprehensive comparisons of the physicochemical properties and anticancer activities of Cur@ZIF-8@HA and Cur@ZIF-8 were conducted. The results indicated that the degradation of Cur during the synthesis of Cur@ZIF-8 was negligible. The obtained Cur@ZIF-8 and Cur@ZIF-8@HA were truncated cubes with hydrodynamic diameters of 174 and 217 nm, respectively. Cur@ZIF-8@HA possessed better stability during storage in different media, a slower drug release rate under neutral and acidic conditions, and a greater inhibitory effect on breast cancer than Cur@ZIF-8. For 4T1 cells, treatment using Cur@ZIF-8@HA induced more cellular uptake and higher cytotoxicity, accompanied by higher lactate dehydrogenase release, cell cycle arrest in G2/M and S phases, production of reactive oxygen species, and apoptosis. In 4T1 tumor-bearing mice models, Cur@ZIF-8@HA showed a stronger inhibitory effect on tumor growth and pulmonary metastasis. Therefore, Cur@ZIF-8@HA might hold great potential as an agent for the effective therapy of breast cancer.

Inhibitory activity and mechanism of trilobatin on tyrosinase: kinetics, interaction mechanism and molecular docking.

Tyrosinase is the rate-limiting enzyme controlling the production of melanin, and tyrosinase inhibitors can regulate the overproduction of melanin by inhibiting tyrosinase activity, which is an effective method to treat pigmentation disorders. In this study, kinetic analysis, multispectroscopic methods and molecular simulation were used to investigate the inhibitory activity and mechanism of trilobatin on tyrosinase. The kinetic analysis showed that trilobatin had significant inhibitory activity on tyrosinase in a reversible and mixed-type manner with IC50 values of (2.24 ± 0.35) × 10-5 mol L-1. The intrinsic fluorescence of tyrosinase was quenched by trilobatin through a static quenching mechanism. Different spectroscopic measurements demonstrated that trilobatin could change the microenvironments and conformation of tyrosinase and molecular docking determined the binding site of quercetin on tyrosinase.

Melatonin retards senescence via regulation of the electron leakage of postharvest white mushroom (Agaricus bisporus).

Currently, melatonin (N-acetyl-5-methoxytrytamine) is recognized as a potential scavenger of free radicals. In this study, the effect of exogenous melatonin at various concentrations (0.05, 0.1, and 0.2 mM) on the texture, sensory qualities, and electron leakage in white mushrooms was evaluated at 3 ± 1 °C. It was observed that mushrooms treated with 0.1 mM melatonin were of good quality and their electron leakage was dramatically dampened. The results showed that 0.1 mM melatonin retained a higher adenosine triphosphate level and also prevented the release of cytochrome c into the cytoplasm. More significantly, it prominently inhibited electron leakage by increasing the activities of complexes I and III by the upregulation of AbNdufB9 and AbRIP1. It also regulated respiratory states in mushrooms; delayed the decline of respiratory state 3; enhanced respiratory state 4; boosted the oxidative phosphorylation and efficiency of mitochondria; and ultimately retarded the senescence of the white mushrooms.

In Vitro Anticancer Potential of Berberis lycium Royle Extracts against Human Hepatocarcinoma (HepG2) Cells.

Human liver cancer has emerged as a serious health concern in the world, associated with poorly available therapies. The Berberis genus contains vital medicinal plants with miraculous healing properties and a wide range of bioactivities. In this study, different crude extracts of B. lycium Royle were prepared and screened against Human Hepatocarcinoma (HepG2) cell lines. The water/ethanolic extract of B. lycium Royle (BLE) exhibited significant antiproliferative activity against the HepG2 cancer cell line with an IC50 value of 47 µg/mL. The extract decreased the clonogenic potential of HepG2 cells in a dose-dependent manner. It induced apoptotic cell death in HepG2 cells that were confirmed by cytometric analysis and microscopic examination of cellular morphology through DAPI-stained cells. Biochemical evidence of apoptosis came from elevating the intracellular ROS level that was accompanied by the loss of mitochondrial membrane potential. The mechanism of apoptosis was further confirmed by gene expression analysis using RT-qPCR that revealed the decline in Bcl-2 independent of p53 mRNA and a rise in CDK1 while downregulating CDK5, CDK9, and CDK10 mRNA levels at 48 h of BLE treatment. The most active fraction was subjected to HPLC which indicated the presence of berberine (48 µg/mL) and benzoic acid (15.8 µg/mL) as major compounds in BLE and a trace amount of luteolin, rutin, and gallic acid. Our study highlighted the importance of the most active BLE extract as an excellent source of nutraceuticals against Human Hepatocarcinoma that can serve as an herbal natural cure against liver cancer.

Au Promoted Nickel-Iron Layered Double Hydroxide Nanoarrays: A Modular Catalyst Enabling High-Performance Oxygen Evolution.

Oxygen evolution reaction (OER) plays a key role in various energy conversion and storage technologies, such as water electrolysis, regenerative fuel cells, and rechargeable metal-air batteries. However, the slow kinetics of OER limit the performance and commercialization of such devices. Herein, we report on NiFe LDH@Au hybrid nanoarrays on Ni foam for much enhanced OER. By hybridization of electronegative Au and NiFe LDH with intrinsic remarkable OER catalytic activity, this modular electrode could drive an overall ultrahigh-performance and robust OER in base with the demand of overpotentials of only 221, 235, and 270 mV to afford 50, 100, and 500 mA cm-2, respectively. Also, it exhibits superior catalytic activity and durability toward OER in 30 wt % KOH.

Versatile molybdenum disulfide based antibacterial composites for in vitro enhanced sterilization and in vivo focal infection therapy.

Biologically, MoS2-based nanostructures have been intensely applied for the photothermal therapy of cancer, but rarely for antibacterial uses. In this contribution, a multifunctional chitosan (CS) functionalized magnetic MoS2 (abbreviated to CFM) was constructed to nonspecifically combat bacterial infection by integrating bacterial conjugation and enrichment, and NIR-triggered photothermal sterilization. Owing to the abundant introduced amino groups, the CFM complex offers a significantly enhanced conjugation efficiency without obvious specificity towards both Gram-positive and -negative bacteria compared to amino-free magnetic MoS2. The magnetic properties of CFM obtained from iron oxide facilitate the enrichment of a CFM-bacteria conjugate, improving the photothermal efficiency of CFM as a photothermal antibacterial agent. Specifically, after being trapped together with bacteria cells, CFM shows an enhanced in vitro photothermal sterilization ability. In vivo S. aureus-induced abscess treatment studies show faster healing when CFM is used as subcutaneous nano-localized heating sources with the assistance of an external magnet to concentrate the CFM-bacteria conjugate. This work establishes an innovative solution and a novel antimicrobial agent for combating bacterial infections without the use of antibiotics, which may open a new area of application and research for MoS2-based nanostructures.

Highly Sensitive and Selective Determination of Tertiary Butylhydroquinone in Edible Oils by Competitive Reaction Induced "On-Off-On" Fluorescent Switch.

As one of most common synthetic phenolic antioxidants, tertiary butylhydroquinone (TBHQ) has received increasing attention due to the potential risk for liver damage and carcinogenesis. Herein, a simple and rapid fluorescent switchable methodology was developed for highly selective and sensitive determination of TBHQ by utilizing the competitive interaction between the photoinduced electron transfer (PET) effect of carbon dots (CDs)/Fe(III) ions and the complexation reaction of TBHQ/Fe(III) ions. This novel fluorescent switchable sensing platform allows determining TBHQ in a wider range from 0.5 to 80 µg mL(-1) with a low detection limit of 0.01 µg mL(-1). Furthermore, high specificity and good accuracy with recoveries ranging from 94.29 to 105.82% in spiked edible oil samples are obtained with the present method, confirming its applicability for the trace detection of TBHQ in a complex food matrix. Thus, the present method provides a novel and effective fluorescent approach for rapid and specific screening of TBHQ in common products, which is beneficial for monitoring and reducing the risk of TBHQ overuse during food storage.

Nickel sulfide microsphere film on Ni foam as an efficient bifunctional electrocatalyst for overall water splitting.

Developing low-cost, efficient, and bifunctional electrocatalysts for both the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is an appealing yet challenging task. Herein, for the first time, a NiS microsphere film was grown in situ on Ni foam (NiS/Ni foam) via a sulfurization reaction as an efficient bifunctional electrocatalyst for overall water splitting with superior activity and good durability. This NiS/Ni foam electrode delivers 20 mA cm(-2) at an overpotential of 158 mV for the HER and 50 mA cm(-2) at an overpotential of 335 mV for the OER in 1.0 M KOH. This bifunctional electrode also enables a high-efficiency alkaline water electrolyzer with 10 mA cm(-2) at a cell voltage of only 1.64 V, which could be promising in water splitting devices for large-scale hydrogen production.

DNA-mediated gold nanoparticle signal transducers for combinatorial logic operations and heavy metal ions sensing.

Herein, the structure of two DNA strands which are complementary except fourteen T-T and C-C mismatches was programmed for the design of the combinatorial logic operation by utilizing the different protective capacities of single chain DNA, part-hybridized DNA and completed-hybridized DNA on unmodified gold nanoparticles. In the presence of either Hg(2+) or Ag(+), the T-Hg(2+)-T or C-Ag(+)-C coordination chemistry could lead to the formation of part-hybridized DNA which keeps gold nanoparticles from clumping after the addition of 40 µL 0.2M NaClO4 solution, but the protection would be screened by 120 µL 0.2M NaClO4 solution. While the coexistence of Hg(2+), Ag(+) caused the formation of completed-hybridized DNA and the protection for gold nanoparticles lost in either 40 µL or 120 µL NaClO4 solutions. Benefiting from sharing of the same inputs of Hg(2+) and Ag(+), OR and AND logic gates were easily integrated into a simple colorimetric combinatorial logic operation in one system, which make it possible to execute logic gates in parallel to mimic arithmetic calculations on a binary digit. Furthermore, two other logic gates including INHIBIT1 and INHIBIT2 were realized to integrated with OR logic gate both for simultaneous qualitative discrimination and quantitative determination of Hg(2+) and Ag(+). Results indicate that the developed logic system based on the different protective capacities of DNA structure on gold nanoparticles provides a new pathway for the design of the combinatorial logic operation in one system and presents a useful strategy for development of advanced sensors, which may have potential applications in multiplex chemical analysis and molecular-scale computer design.

A one-step approach to the large-scale synthesis of functionalized MoS2 nanosheets by ionic liquid assisted grinding.

A prerequisite for exploiting most proposed applications for MoS2 is the availability of water-dispersible functionalized MoS2 nanosheets in large quantities. Here we report one-step synthesis and surface functionalization of MoS2 nanosheets by a facile ionic liquid assisted grinding method in the presence of chitosan. The selected ionic liquid with suitable surface energy could efficiently overcome the van der Waals force between the MoS2 layers. Meanwhile, chitosan molecules bind to the plane of MoS2 sheets non-covalently, which prevents the reassembling of exfoliated MoS2 sheets and facilitates the exfoliation progress. The obtained chitosan functionalized MoS2 nanosheets possess favorable stability and biocompatibility, which renders them as promising and biocompatible near-infrared agents for photothermal ablation of cancer. This contribution provides a facile way for the green, one-step and large-scale synthesis of advanced functional MoS2 materials.

The inhibitory effect of selenium nanoparticles on protein glycation in vitro.

Selenium nanoparticles (Se NPs) possess well-known excellent biological activities and low toxicity, and have been employed for numerous applications except as inhibitors to protein glycation. Herein, the present study is carried out to investigate the inhibitory effect of Se NPs on protein glycation in a bovine serum albumin (BSA)/glucose system. By measuring the amount of glucose covalently bound onto BSA, the formation of fructosamine and fluorescent products, it is found that Se NPs can hinder the development of protein glycation in a dose-dependent but time-independent manner under the selected reaction conditions (55 °C, 40 h). And after comparing the increase of inhibitory rate in different stages, it is observed that Se NPs show the greatest inhibitory effect in the early stage, then in the advanced stage, but no effect in the intermediate stage. Fourier transform infrared spectroscopy characterization of Se NPs collected after glycation and determination of ·OH influence and glyoxal formation show that the mechanism for the inhibitory efficacy of Se NPs is related to their strong competitive activity against available amino groups in proteins, their great scavenging activity on reactive oxygen species and their inhibitory effect on α-dicarbonyl compounds' formation. In addition, it is proved that Se NPs protect proteins from structural modifications in the system and they do not exhibit significant cytotoxicity towards BV-2 and BRL-3A cells at low concentrations (10 and 50 µg mL(-1)). Consequently, Se NPs may be suitable for further in vivo studies as novel anti-glycation agents.

Facile colorimetric method for simple and rapid detection of endotoxin based on counterion-mediated gold nanorods aggregation.

Existence of endotoxin in food and injection products indicates bacterial contaminations and therefore poses threat to human health. Herein, a simple and rapid colorimetric method for the effective detection of endotoxin in food and injections based on counterion-mediated gold nanorods aggregation is first proposed. By taking advantage of the color change of unmodified gold nanorods resulted from endotoxin mediated gold nanorods aggregation, endotoxin could be detected in the concentration range of 0.01-0.6 µM. Further, we studied the performance of gold nanorods with different aspect ratios (2.7 and 3.3) in determination of endotoxin and found that gold nanorods with higher aspect ratio (AR) showed superiority in the sensing sensitivity of endotoxin. A good specificity for endotoxin, a detection limit of 0.0084 µM and recoveries ranging from 84% to 109% in spiked food and injection samples are obtained with the colorimetric method. Results demonstrate that the present method provides a novel and effective approach for on-site screening of endotoxin in common products, which is beneficial for monitoring and reducing the risk of bacterial contaminations in food and injections production.