Plasma-Induced Oxidation Products of (–)-Epigallocatechin Gallate with Digestive Enzymes Inhibitory Effects

(−)-Epigallocatechin gallate (EGCG), the chief dietary constituent in green tea (Camellia sinensis), is relatively unstable under oxidative conditions. This study evaluated the use of non-thermal dielectric barrier discharge (DBD) plasma to improve the anti-digestive enzyme capacities of EGCG oxidation products. Pure EGCG was dissolved in an aqueous solution and irradiated with DBD plasma for 20, 40, and 60 min. The reactant, irradiated for 60 min, exhibited improved inhibitory properties against α-glucosidase and α-amylase compared with the parent EGCG. The chemical structures of these oxidation products 1–3 from the EGCG, irradiated with the plasma for 60 min, were characterized using spectroscopic methods. Among the oxidation products, EGCG quinone dimer A (1) showed the most potent inhibitory effects toward α-glucosidase and α-amylase with IC₅₀ values of 15.9 ± 0.3 and 18.7 ± 0.3 μM, respectively. These values were significantly higher than that of the positive control, acarbose. Compound 1, which was the most active, was the most abundant in the plasma-irradiated reactant for 60 min according to quantitative high-performance liquid chromatography analysis. These results suggest that the increased biological capacity of EGCG can be attributed to the structural changes to EGCG in H₂O, induced by cold plasma irradiation.     

Metagenomics Approach to the Intestinal Microbiome Structure and Abundance in High-Fat-Diet-Induced Hyperlipidemic Rat Fed with (−)-Epigallocatechin-3-Gallate Nanoparticles

The effects of nanoparticles (NPs) on microbiota homeostasis and their physiological relevance are still unclear. Herein, we compared the modulation and consequent pharmacological effects of oral administration of (−)-epigallocatechin-3-gallate (EGCG)-loaded β-cyclodextrin (β-CD) NPs (EGCG@β-CD NPs) and EGCG on gut microbiota. EGCG@β-CD NPs were prepared using self-assembly and their influence on the intestinal microbiome structure was analyzed using a metagenomics approach. The “Encapsulation efficiency (EE), particle size, polydispersity index (PDI), zeta potential” of EGCG@β-CD NPs were recorded as 98.27 ± 0.36%, 124.6 nm, 0.313 and –24.3 mV, respectively. Surface morphology of EGCG@β-CD NPs was observed as spherical. Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and molecular docking studies confirmed that EGCG could be well encapsulated in β-CD and formed as EGCG@β-CD NPs. After being continuously administered EGCG@β-CD NPs for 8 weeks, the serum cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and liver malondialdehyde (MDA) levels in the rats were significantly decreased, while the levels of catalase (CAT) and apolipoprotein-A1 (apo-A1) in the liver increased significantly in the hyperlipidemia model of rats, when compared to the high-fat-diet group. Furthermore, metagenomic analysis revealed that the ratio of Verrucomicrobia/Bacteroidetes was altered and Bacteroidetes decreased in the high-fat diet +200 mg/kg·bw EGCG@β-CD NPs group, while the abundance of Verrucomicrobia was significantly increased, especially Akkermansia muciniphila in rat feces. EGCG@β-CD NPs could be a promising EGCG delivery strategy to modulate the gut microbiota, enhancing its employment in the prevention of hyperlipidemia.     

Structural and Functional Changes of Reconstituted High-Density Lipoprotein (HDL) by Incorporation of α-synuclein: A Potent Antioxidant and Anti-Glycation Activity of α-synuclein and apoA-I in HDL at High Molar Ratio of α-synuclein

α-synuclein (α-syn) is a major culprit of Parkinson’s disease (PD), although lipoprotein metabolism is very important in the pathogenesis of PD. α-syn was expressed and purified using the pET30a expression vector from an E. coli expression system to elucidate the physiological effects of α-syn on lipoprotein metabolism. The human α-syn protein (140 amino acids) with His-tag (8 amino acids) was expressed and purified to at least 95% purity. Isoelectric focusing gel electrophoresis showed that the isoelectric point (pI) of α-syn and apoA-I were pI = 4.5 and pI = 6.4, respectively. The lipid-free α-syn showed almost no phospholipid-binding ability, while apoA-I showed rapid binding ability with a half-time (T_1/2) = 8 ± 0.7 min. The α-syn and apoA-I could be incorporated into the reconstituted HDL (rHDL, molar ratio 95:5:1:1, palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC):cholesterol:apoA-I:α-syn with the production of larger particles (92 Å) than apoA-I-rHDL (86 and 78 Å) and α-syn-rHDL (65 Å). An rHDL containing both apoA-I and α-syn showed lower α-helicity around 45% with a red shift of the Trp wavelength maximum fluorescence (WMF) from 339 nm, while apoA-I-HDL showed 76% α-helicity and 337 nm of WMF. The denaturation by urea addition showed that the incorporation of α-syn in rHDL caused a larger increase in the WMF than apoA-I-rHDL, suggesting that the destabilization of the secondary structure of apoA-I by the addition of α-syn. On the other hand, the addition of α-syn induced two-times higher resistance to rHDL glycation at apoA-I:α-syn molar ratios of 1:1 and 1:2. Interestingly, low α-syn in rHDL concentrations, molar ratio of 1:0.5 (apoA-I:α-syn), did not prevent glycation with more multimerization of apoA-I. In the lipid-free and lipid-bound state, α-syn showed more potent antioxidant activity than apoA-I against cupric ion-mediated LDL oxidation. On the other hand, microinjection of α-syn (final 2 μM) resulted in 10% less survival of zebrafish embryos than apoA-I. A subcutaneous injection of α-syn (final 34 μM) resulted in less tail fin regeneration than apoA-I. Interestingly, incorporation of α-syn at a low molar ratio (apoA-I:α-syn, 1:0.5) in rHDL resulted destabilization of the secondary structure and impairment of apoA-I functionality via more oxidation and glycation. However, at a higher molar ratio of α-syn in rHDL (apoA-I:α-syn = 1:1 or 1:2) exhibited potent antioxidant and anti-glycation activity without aggregation. In conclusion, there might be a critical concentration of α-syn and apoA-I in HDL-like complex to prevent the aggregation of apoA-I via structural and functional enhancement.     

Metal-organic framework MIL-53(Al): synthesis,catalytic performance for the Friedel-Crafts acylation,and reaction mechanism

Metal-organic framework MIL-53(Al) was synthesized by a solvothermal method using aluminum nitrate as the aluminium source and 1,4-benzenedicarboxylic acid (H₂BDC) as the organic ligand. The structure of samples was characterized by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). The catalytic activity and recyclability of MIL-53(Al) catalyst for the Friedel-Crafts acylation reaction of indole with benzoyl chloride were evaluated. The reaction conditions were optimized and a reaction mechanism was suggested. The results showed that the MIL-53(Al) catalyst exhibited good catalytic activity and recyclability for the Friedel-Crafts acylation reaction. When the molar ratio of indole and MIL-53(Al) catalyst was 1:0.06 (n ₁:n _catalyst), the molar ratio of indole and benzoyl chloride was 1:3, and the solvent was dichloromethane, the conversion of indole could reach 97.1% and the selectivity of 3-acylindole could reach 81.1% at 25 °C after 8 h. The catalyst can be reused without significant degradation in catalytic activity. After the catalyst was reused five times, the conversion of indole was 87.6% and the selectivity of 3-acylindole was 79.5%.     

Novel Perbutyrylated Glucose Derivatives of (–)-Epigallocatechin-3-Gallate Inhibit Cancer Cells Proliferation by Decreasing Phosphorylation of the EGFR: Synthesis,Cytotoxicity, and Molecular Docking

Lung cancer is one of the most commonly occurring cancer mortality worldwide. The epidermal growth factor receptor (EGFR) plays an important role in cellular functions and has become the new promising target. Natural products and their derivatives with various structures, unique biological activities, and specific selectivity have served as lead compounds for EGFR. D-glucose and EGCG were used as starting materials. A series of glucoside derivatives of EGCG (7–12) were synthesized and evaluated for their in vitro anticancer activity against five human cancer cell lines, including HL-60, SMMC-7721, A-549, MCF-7, and SW480. In addition, we investigated the structure-activity relationship and physicochemical property–activity relationship of EGCG derivatives. Compounds 11 and 12 showed better growth inhibition than others in four cancer cell lines (HL-60, SMMC-7721, A-549, and MCF), with IC₅₀ values in the range of 22.90–37.87 μM. Compounds 11 and 12 decreased phosphorylation of EGFR and downstream signaling protein, which also have more hydrophobic interactions than EGCG by docking study. The most active compounds 11 and 12, both having perbutyrylated glucose residue, we found that perbutyrylation of the glucose residue leads to increased cytotoxic activity and suggested that their potential as anticancer agents for further development.     

Synthesis,Characterization, DFT and Photocatalytic Studies of a New Pyrazine Cadmium(II) Tetrakis(4-methoxy-phenyl)-porphyrin Compound

This study describes the synthesis, theoretical investigations, and photocatalytic degradational properties of a new (pyrazine)(meso-tetrakis(4-tert-methoxyphenyl)-porphyrinato)-cadmium (II) ([Cd(TMPP)-Pyz]) complex (1). The new penta-coordinated Cd^II porphyrin complex (1) was characterized by various spectroscopic techniques, including FT-IR, NMR, UV-visible absorption, fluorescence emission, and singlet oxygen, while its molecular structure was studied using single crystal X-ray diffraction. The UV–Vis spectroscopic study highlighted the redshift of the absorption bands after the insertion of the Cd(II) metal ion into the TMPP ring. The co-coordination of the pyrazine axial ligand enhanced this effect. A fluorescence emission spectroscopic study showed a significant blueshift in the Q bands, accompanied by a decrease in the fluorescence emission intensity and quantum yields of Φ_f = 0.084, Φ_f = 0.06 and Φ_f = 0.03 for H₂-TMPP free-base porphyrin, [Cd(TMPP)] and [Cd(TMPP)(Pyz)] (1) respectively. Singlet oxygen revealed that the H₂-TMPP porphyrin produced the most efficient singlet oxygen quantum yield of (Φ_Δ = 0.73) compared to [CdTMPP] (Φ_Δ = 0.57) and [Cd(TMPP)(Pyz)] (1) (Φ_Δ = 0.13). In the crystal lattice, the [Cd(TMPP)Pyz] was stabilized through non-covalent intermolecular interactions (NCI), such as the hydrogen bonds C-H···N and C-H···Cg. Additionally, crystal explorer software was then utilized to measure the quantitative analysis of the intermolecular interactions in the unit cell of the crystal structure and established that the C-H···π interaction dominated. The Natural bond orbital (NBO) analysis revealed that each molecule is stabilized by hyperconjugation and charge delocalization. As a photocatalyst, the coordination complex 1 showed excellent photocatalytic activity toward the degradation of Levafix Blue CA reactive dye (i.e., dye photo-degradation of 80%).     

An Optimization Procedure for Preparing Aqueous CAR/HP-CD Aggregate Dispersions

β-Carotene is a very important molecule for human health. It finds a large application in the food industry, especially for the development of functional foods and dietary supplements. However, β-carotene is an unstable compound and is sensitive to light, temperature, and oxygen. To overcome those limitations, various delivery systems were developed. The inclusion of β-carotene by cyclodextrin aggregates is attractive due to non-toxicity, low hygroscopicity, stability, and the inexpensiveness of cyclodextrins. In this study, β-carotene/2-hydroxypropyl-β-cyclodextrin aggregates were prepared based on the procedure of the addition of β-carotene in an organic solvent to the hot water dispersion of 2-hydroxypropyl-β-cyclodextrin and the following instant evaporation of the organic solvent. The best conditions for the aggregate preparation were found to be as follows: 25% concentration of 2-hydroxypropyl-β-cyclodextrin in water, 65 °C temperature, and acetone for β-carotene dissolution. The efficiency of entrapping was equal to 88%. The procedure is attractive due to the short time of the aggregate preparation.     

Cryosynthesis,structure, and spectroscopic properties of aluminum chloride—cobalt(ii) chloride complexes: experiment and calculations

Products of co-condensation of aluminum chloride and cobalt(ii) chloride vapors were studied by low-temperature (80—200 K) IR spectroscopy. In addition to 2 : 1 complexes, previously unknown equimolar associates were found and their IR spectra were investigated. Quantum-mechanical calculations were carried out including electron correlation with the use of the B3LYP and PBE density functionals. The geometric structures were optimized and harmonic vibrational frequencies of the molecules of aluminum chloride, cobalt chloride, and their complexes with different compositions were calculated. Under conditions of limited molecular mobility, the (AlCl₃)₂·CoCl₂ complexes can be stabilized in structures containing the Co atom in a tetrahedral or distorted octahedral environment. Their thermal stability limits were determined. It was found that labile ionic species are generated in the reactions of aluminum chloride complexes with cobalt chloride with different compositions at 120—170 K.     

Elucidation of Interaction between Whey Proteins and Proanthocyanidins and Its Protective Effects on Proanthocyanidins during In-Vitro Digestion and Storage

Whey proteins and oligomeric proanthocyanidins have nutritional value and are widely used in combination as food supplements. However, the effect of the interactions between proanthocyanidins and whey proteins on their stability has not been studied in depth. In this work, we aimed to characterize the interactions between β-Lactoglobulin (β-LG) and α-lactalbumin (α-LA) and oligomeric proanthocyanidins, including A1, A2, B1, B2, B3, and C1, using multi-spectroscopic and molecular docking methods. Fluorescence spectroscopic data revealed that all of the oligomeric proanthocyanidins quenched the intrinsic fluorescence of β-LG or α-LA by binding-related fluorescence quenching. Among the six oligomeric proanthocyanidins, A1 showed the strongest affinity for β-LG (K_a = 2.951 (±0.447) × 10⁴ L∙mol⁻¹) and α-LA (K_a = 1.472 (±0.236) × 10⁵ L∙mol⁻¹) at 297 K. β-LG/α-LA and proanthocyanidins can spontaneously form complexes, which are mainly induced by hydrophobic interactions, hydrogen bonds, and van der Waals forces. Fourier-transform infrared spectroscopy (FTIR) and circular dichroism spectroscopy showed that the secondary structures of the proteins were rearranged after binding to oligomeric proanthocyanidins. During in vitro gastrointestinal digestion, the recovery rate of A1 and A2 increased with the addition of WPI by 11.90% and 38.43%, respectively. The addition of WPI (molar ratio of 1:1) increased the retention rate of proanthocyanidins A1, A2, B1, B2, B3, and C1 during storage at room temperature by 14.01%, 23.14%, 30.09%, 62.67%, 47.92%, and 60.56%, respectively. These results are helpful for the promotion of protein–proanthocyanidin complexes as functional food ingredients in the food industry.     

Solid-State Structures and Photoluminescence of Lamellar Architectures of Cu(I) and Ag(I) Paddlewheel Clusters with Hydrogen-Bonded Polar Guests

Two hexanuclear paddlewheel-like clusters appending six carboxylic-acid pendants have been isolated with the inclusion of polar solvent guests: [Cu₆(Hmna)₆]·7DMF (1·7DMF) and [Ag₆(Hmna)₆]·8DMSO (2·8DMSO), where H₂mna = 2-mercaptonicotininc acid, DMF = N,N’-dimethylformamide, and DMSO = dimethyl sulfoxide. The solvated clusters, together with their fully desolvated forms 1 and 2, have been characterized by FTIR, UV–Vis diffuse reflectance spectroscopy, TG-DTA analysis, and DFT calculations. Crystal structures of two solvated clusters 1·7DMF and 2·8DMSO have been unambiguously determined by single-crystal X-ray diffraction analysis. Six carboxylic groups appended on the clusters trap solvent guests, DMF or DMSO, through H-bonds. As a result, alternately stacked lamellar architectures comprising of a paddlewheel cluster layer and H-bonded solvent layer are formed. Upon UV illumination (λ_ex = 365 nm), the solvated hexasilver(I) cluster 2·8DMSO gives intense greenish-yellow photoluminescence in the solid state (λ_PL = 545 nm, Φ_PL = 0.17 at 298 K), whereas the solvated hexacopper(I) cluster 1·7DMF displays PL in the near-IR region (λ_PL = 765 nm, Φ_PL = 0.38 at 298 K). Upon complete desolvation, a substantial bleach in the PL intensity (Φ_PL < 0.01) is observed. The desorption–sorption response was studied by the solid-state PL spectroscopy. Non-covalent interactions in the crystal including intermolecular H-bonds, CH⋯π interactions, and π⋯π stack were found to play decisive roles in the creation of the lamellar architectures, small-molecule trap-and-release behavior, and guest-induced luminescence enhancement.     

Identification of Dipeptidyl Peptidase-4 and α-Amylase Inhibitors from Melicope glabra (Blume) T. G. Hartley (Rutaceae) Using Liquid Chromatography Tandem Mass Spectrometry,In Vitro and In Silico Methods

The present study investigated the antidiabetic properties of the extracts and fractions from leaves and stem bark of M. glabra based on dipeptidyl peptidase-4 (DPP-4) and α-Amylase inhibitory activity assays. The chloroform extract of the leaves was found to be most active towards inhibition of DPP-4 and α-Amylase with IC₅₀ of 169.40 μg/mL and 303.64 μg/mL, respectively. Bioassay-guided fractionation of the leaves’ chloroform extract revealed fraction 4 (CF4) as the most active fraction (DPP-4 IC₅₀: 128.35 μg/mL; α-Amylase IC₅₀: 170.19 μg/mL). LC-MS/MS investigation of CF4 led to the identification of trans-decursidinol (1), swermirin (2), methyl 3,4,5-trimethoxycinnamate (3), renifolin (4), 4′,5,6,7-tetramethoxy-flavone (5), isorhamnetin (6), quercetagetin-3,4′-dimethyl ether (7), 5,3′,4′-trihydroxy-6,7-dimethoxy-flavone (8), and 2-methoxy-5-acetoxy-fruranogermacr-1(10)-en-6-one (9) as the major components. The computational study suggested that (8) and (7) were the most potent DPP-4 and α-Amylase inhibitors based on their lower binding affinities and extensive interactions with critical amino acid residues of the respective enzymes. The binding affinity of (8) with DPP-4 (−8.1 kcal/mol) was comparable to that of sitagliptin (−8.6 kcal/mol) while the binding affinity of (7) with α-Amylase (−8.6 kcal/mol) was better than acarbose (−6.9 kcal/mol). These findings highlight the phytochemical profile and potential antidiabetic compounds from M. glabra that may work as an alternative treatment for diabetes.     

Extraction of Anthocyanins from Borage (Echium amoenum) Flowers Using Choline Chloride and a Glycerol-Based,Deep Eutectic Solvent: Optimization,Antioxidant Activity,and In Vitro Bioavailability

Borage flower (Echium amoenum), an annual herb native to the Mediterranean region, is an excellent source of anthocyanins and is widely used in various forms due to its biological activities. In the present study, a choline chloride and glycerol (CHGLY)-based natural deep eutectic solvent (NADES) was applied in order to extract the anthocyanins from borage flowers. The traditional solvents, including water, methanol, and ethanol, were used to evaluate the efficiency of CHGLY. The results showed that CHGLY was highly efficient compared to the traditional solvents, providing the highest amounts of the total anthocyanin content (TAC), total phenolic content (TPC), total flavonoid content (TFC), individual anthocyanins, and antioxidant activity (DPPH radical scavenging (DPPH) and ferric-reducing antioxidant power (FRAP) assays). The most dominant anthocyanin found in studied borage was cyanidin-3-glucoside, followed by cyanin chloride, cyanidin-3-rutinoside, and pelargonidin-3-glucoside. The bioavailability % was 71.86 ± 0.47%, 77.29 ± 0.57%, 80.22 ± 0.65%, and 90.95 ± 1.01% for cyanidin-3-glucoside, cyanidin-3-rutinoside, by pelargonidin-3-glucoside and cyanin chloride, respectively. However, cyanidin-3-glucoside was the anthocyanin compound showing the highest stability (99.11 ± 1.66%) in the gastrointestinal environment. These results suggested that choline chloride and glycerol-based NADES is not only an efficient, eco-friendly solvent for the extraction of anthocyanins but can also be used to increase the bioavailability of anthocyanins.     

Discovery of Novel Coumarin Derivatives as Potential Dual Inhibitors against α-Glucosidase and α-Amylase for the Management of Post-Prandial Hyperglycemia via Molecular Modelling Approaches

Coumarin derivatives are proven for their therapeutic uses in several human diseases and disorders such as inflammation, neurodegenerative disorders, cancer, fertility, and microbial infections. Coumarin derivatives and coumarin-based scaffolds gained renewed attention for treating diabetes mellitus. The current decade witnessed the inhibiting potential of coumarin derivatives and coumarin-based scaffolds against α-glucosidase and α-amylase for the management of postprandial hyperglycemia. Hyperglycemia is a condition where an excessive amount of glucose circulates in the bloodstream. It occurs when the body lacks enough insulin or is unable to correctly utilize it. With open-source and free in silico tools, we have investigated novel 80 coumarin derivatives for their inhibitory potential against α-glucosidase and α-amylase and identified a coumarin derivative, CD-59, as a potential dual inhibitor. The ligand-based 3D pharmacophore detection and search is utilized to discover diverse coumarin-like compounds and new chemical scaffolds for the dual inhibition of α-glucosidase and α-amylase. In this regard, four novel coumarin-like compounds from the ZINC database have been discovered as the potential dual inhibitors of α-glucosidase and α-amylase (ZINC02789441 and ZINC40949448 with scaffold thiophenyl chromene carboxamide, ZINC13496808 with triazino indol thio phenylacetamide, and ZINC09781623 with chromenyl thiazole). To summarize, we propose that a coumarin derivative, CD-59, and ZINC02789441 from the ZINC database will serve as potential lead molecules with dual inhibition activity against α-glucosidase and α-amylase, thereby discovering new drugs for the effective management of postprandial hyperglycemia. From the reported scaffold, the synthesis of several novel compounds can also be performed, which can be used for drug discovery.     

Oligomer Sensor Nanoarchitectonics for “Turn-On” Fluorescence Detection of Cholesterol at the Nanomolar Level

Sensitive and rapid monitoring of cholesterol levels in the human body are highly desirable as they are directly related to the diagnosis of cardiovascular diseases. By using the nanoarchitectonic approach, a novel fluorescent conjugated oligofluorene (OFP-CD) functionalized with β-cyclodextrin (β-CD) was assembled for “Turn-On” fluorescence sensing of cholesterol. The appended β-CD units in OFP-CD enabled the forming of host-guest complexes with dabsyl chloride moieties in water, resulting in fluorescence quenching of the oligofluorene through intermolecular energy transfer. In the presence of cholesterol molecules, a more favorable host-guest complex with stoichiometry 1 cholesterol: 2 β-CD units was formed, replacing dabsyl chloride in β-CD’s cavities. This process resulted in fluorescence recovery of OFP-CD, owing to disruption of energy transfer. The potential of this nanoarchitectonic system for “Turn-On” sensing of cholesterol was extensively studied by fluorescence spectroscopy. The high selectivity of the sensor for cholesterol was demonstrated using biologically relevant interfering compounds, such as carbohydrates, amino acids, metal ions, and anions. The detection limit (LOD value) was as low as 68 nM, affirming the high sensitivity of the current system.     

Insulin Complexation with Cyclodextrins—A Molecular Modeling Approach

Around 5% of the population of the world is affected with the disease called diabetes mellitus. The main medication of the diabetes is the insulin; the active form is the insulin monomer, which is an instable molecule, because the long storage time, or the high temperature, can cause the monomer insulin to adapt an alternative fold, rich in β-sheets, which is pharmaceutically inactive. The aim of this study is to form different insulin complexes with all the cyclodextrin used for pharmaceutical excipients (native cyclodextrin, methyl, hydroxyethyl, hydroxypropyl and sulfobutylether substituted β-cyclodextrin), in silico condition, with the AutoDock molecular modeling program, to determine the best type of cyclodextrin or cyclodextrin derivate to form a complex with an insulin monomer, to predict the molar ratio, the conformation of the complex, and the intermolecular hydrogen bonds formed between the cyclodextrin and the insulin. From the results calculated by the AutoDock program it can be predicted that insulin can make a stable complex with 5–7 molecules of hydroxypropyl-β-cyclodextrin or sulfobutylether-β-cyclodextrin, and by forming a complex potentially can prevent or delay the amyloid fibrillation of the insulin and increase the stability of the molecule.     

Fabrication and Biological Assessment of Antidiabetic α-Mangostin Loaded Nanosponges: In Vitro,In Vivo,and In Silico Studies

Type 2 diabetes mellitus has been a major health issue with increasing morbidity and mortality due to macrovascular and microvascular complications. The urgent need for improved methods to control hyperglycemic complications reiterates the development of innovative preventive and therapeutic treatment strategies. In this perspective, xanthone compounds in the pericarp of the mangosteen fruit, especially α-mangostin (MGN), have been recognized to restore damaged pancreatic β-cells for optimal insulin release. Therefore, taking advantage of the robust use of nanotechnology for targeted drug delivery, we herein report the preparation of MGN loaded nanosponges for anti-diabetic therapeutic applications. The nanosponges were prepared by quasi-emulsion solvent evaporation method. Physico-chemical characterization of formulated nanosponges with satisfactory outcomes was performed with Fourier transform infra-red (FTIR) spectroscopy, differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Zeta potential, hydrodynamic diameter, entrapment efficiency, drug release properties, and stability studies at stress conditions were also tested. Molecular docking analysis revealed significant interactions of α-glucosidase and MGN in a protein-ligand complex. The maximum inhibition by nanosponges against α-glucosidase was observed to be 0.9352 ± 0.0856 µM, 3.11-fold higher than acarbose. In vivo studies were conducted on diabetic rats and plasma glucose levels were estimated by HPLC. Collectively, our findings suggest that MGN-loaded nanosponges may be beneficial in the treatment of diabetes since they prolong the antidiabetic response in plasma and improve patient compliance by slowly releasing MGN and requiring less frequent doses, respectively.     

The Synthesis of a Bis(thiosemicarbazone) Macrocyclic Ligand and the Mn(II), Co(II), Zn(II) and 68Ga(III) Complexes

A 1,4,7,10-tetraazacyclododecane (cyclen) variant bearing two thiosemicarbazone pendant groups has been prepared. The ligand forms complexes with Mn²⁺, Co²⁺ and Zn²⁺. X-ray crystallography of the Mn²⁺, Co²⁺ and Zn²⁺ complexes showed that the ligand provides a six-coordinate environment for the metal ions. The Mn²⁺ and Zn²⁺ complexes exist in the solid state as racemic mixtures of the Δ(δ,δ,δ,δ)/Λ(λ,λ,λ,λ) and Δ(λ,λ,λ,λ)/Λ(δ,δ,δ,δ) diastereomers, and the Co²⁺ complex exists as the Δ(δ,δ,δ,δ)/Λ(λ,λ,λ,λ) and Δ(λ,λ,λ,δ)/Λ(δ,δ,δ,λ) diastereomers. Density functional theory calculations indicated that the relative energies of the diastereomers are within 10 kJ mol⁻¹. Magnetic susceptibility of the complexes indicated that both the Mn²⁺ and Co²⁺ ions are high spin. The ligand was radiolabelled with gallium-68, in the interest of developing new positron emission tomography imaging agents, which produced a single species in high radiochemical purity (>95%) at 90 °C for 10 min.     

Thermal Degradation of Linalool-Chemotype Cinnamomum osmophloeum Leaf Essential Oil and Its Stabilization by Microencapsulation with β-Cyclodextrin

The thermal degradation of linalool-chemotype Cinnamomum osmophloeum leaf essential oil and the stability effect of microencapsulation of leaf essential oil with β-cyclodextrin were studied. After thermal degradation of linalool-chemotype leaf essential oil, degraded compounds including β-myrcene, cis-ocimene and trans-ocimene, were formed through the dehydroxylation of linalool; and ene cyclization also occurs to linalool and its dehydroxylated products to form the compounds such as limonene, terpinolene and α-terpinene. The optimal microencapsulation conditions of leaf essential oil microcapsules were at a leaf essential oil to the β-cyclodextrin ratio of 15:85 and with a solvent ratio (ethanol to water) of 1:5. The maximum yield of leaf essential oil microencapsulated with β-cyclodextrin was 96.5%. According to results from the accelerated dry-heat aging test, β-cyclodextrin was fairly stable at 105 °C, and microencapsulation with β-cyclodextrin can efficiently slow down the emission of linalool-chemotype C. osmophloeum leaf essential oil.