Omeprazole inhibits α-glucosidase activity and the formation of nonenzymatic glycation products: Activity and mechanism.

In this study, the inhibitory effect and mechanism of omeprazole on α-glucosidase and nonenzymatic glycation were investigated in vitro by using multi-spectroscopic methods and molecular docking. Enzyme kinetic results showed that omeprazole inhibited α-glucosidase in a reversible and noncompetitive manner (IC50= 0.595 ± 0.003 mM). The results from fluorescence quenching and thermomechanical analyses signified that omeprazole reduced the fluorescence intensity of α-glucosidase by forming an omeprazole-α-glucosidase complex primarily driven by hydrogen bonds. Molecular docking further confirmed that hydrogen bonds and hydrophobic forces were the major driving forces for omeprazole binding to α-glucosidase. The nonenzymatic glycation assays revealed that omeprazole had a moderate inhibition against the formation of fructosamine, dicarbonyl compounds, and advanced glycation end products (AGEs). This study provides a new inhibitor of both α-glucosidase and nonenzymatic glycation and provides a practicable candidate for treating diabetes and its complications.

Effect of ascorbic acid on tyrosinase and its anti-browning activity in fresh-cut Fuji apple.

Tyrosinase (polyphenol oxidase) is the key enzyme of enzymatic browning in fruits and vegetables. In this research, the impact of ascorbic acid on tyrosinase and its anti-browning effect on fresh-cut Fuji apple were investigated. Ascorbic acid had a dual effect on tyrosinase with a half inhibitory concentration (IC50 ) of 13.40 ± 0.05 µM. Fluorescence assay demonstrated that ascorbic acid interacted with tyrosinase in a dynamic contaction caused by Förster's resonance energy transfer (FRET) and induced a conformational change of the enzyme. Thermodynamic analysis, copper interaction, and molecular docking further confirmed that ascorbic acid could chelate the copper ions located in active center and interact with amino acid residues of tyrosinase via hydrophobic interaction. In addition, ascorbic acid prevented the browning of fresh-cut apples by increasing APX activity and inhibiting PPO and POD activities which reduce the oxidation of total phenolics and flavonoids. PRACTICAL APPLICATIONS: The present study demonstrated that ascorbic acid had a strong inhibitory activity against tyrosinase (IC50 = 13.40 ± 0.05 µM) and anti-browning activity against fresh-cut Fuji apple. It could delay the browning degree of apple juice, increase APX activity, inhibit PPO and POD activities, and reduce the oxidation of total phenolics and flavonoids. These findings provided a basis for the feasible application of ascorbic acid on the preservation of fruits.

Biodegradable water-based polyurethane scaffolds with a sequential release function for cell-free cartilage tissue engineering.

Three-dimensional (3D) printing technology has rapidly developed as a promising technology for manufacturing tissue engineering scaffolds. Cells used in tissue engineering are subjected to the quality management and risk of contamination, while cell-free scaffolds may not have sufficient therapeutic efficacy. In this study, water-based 3D printing ink containing biodegradable polyurethane (PU), chemokine SDF-1, and Y27632 drug-embedding PU microspheres was printed at low temperature (-40 °C) to fabricate tissue engineering scaffolds with sequential drug release function. The scaffolds containing 200 ng/ml SDF-1 and 22 wt% Y27632-encapsulated microspheres (55 µg/ml Y27632 in microspheres) (abbreviated PU/SDF-1/MS_Y scaffolds) had the optimal performance. The structural design of the scaffolds allowed each of SDF-1 and Y27632 to be released sequentially in vitro and reach the effective concentration (∼100 ng/ml and 3.38 µg/ml, respectively) after the appropriate time (24 h and 62 h, respectively). Human mesenchymal stem cells (hMSCs) seeded in the scaffolds showed significant GAG deposition in 7 days. Besides, the gradual release of SDF-1 from the PU/SDF-1/MS_Y scaffolds could induce the migration of hMSCs. Implantation of the cell-free PU/SDF-1/MS_Y scaffolds in rabbit articular cartilage defects supported the potential of the scaffolds to promote cartilage regeneration. The 3D printed scaffolds with sequential releases of SDF-1 and Y27632 may have potential in cartilage tissue engineering. STATEMENT OF SIGNIFICANCE: The clinical success of tissue engineering depends highly on the quality of externally supplied cells, while cell-free scaffolds may not have sufficient therapeutic efficacy. In this manuscript, water-based 3D printing ink containing biodegradable polyurethane (PU), chemokine SDF-1, and Y27632 drug-embedding PU microspheres was printed at low temperature to fabricate tissue engineering scaffolds with sequential drug release function. The structural design of the scaffolds allowed each of SDF-1 and Y27632 to be released sequentially in vitro. SDF-1 was released earlier from the scaffolds to promote cell migration. The drug Y27632 was released later from the microspheres into the matrix of the scaffolds to induce the chondrogenic differentiation of the attracted cells. Implantation of the cell-free PU/SDF-1/MS_Y scaffolds in rabbit articular cartilage defects supported the potential of the scaffolds to promote cartilage regeneration. We hypothesized that the cell-free scaffolds may improve the clinical applicability and convenience without the use of exogenous cells or growth factor.