Cycloartanes from leaves of Combretum quadrangulare growing in Vietnam.

Two new cycloartanes, combretic acid C (1) and combretanone I (3), were isolated from the leaves of Combretum quadrangulare Kurz, together with the previously-reported combretic acids A-B (2 and 5) and combretanone A (4). An extensive set of spectroscopic methods were used to elucidate the structures of these compounds. Cytotoxicity against the K562 cancer cell line was evaluated. Compound 1 showed strong activity, with an IC50 value of 9.7 µM. The other compounds showed moderate activity. Alpha-glucosidase inhibition was also evaluated. The isolated compounds showed moderate inhibition, with IC50 values in the range 102.2-194.7 µM.

Determination of the Assigned Values of Blood Cells by an Impedance Method for Hematological Reference Samples Used in Hematology External Quality Assessment (EQA) Programs.

The research into and production of hematological reference samples used to implement an external quality assessment (EQA) to check the quality of hematology tests are necessary for hematology laboratories in Vietnam. In this research, the study team determined the assessment values of blood cell count (human RBCs, pseudo-leucocytes, and pseudo-platelets) by the impedance method used in hematology EQA programs. The hematological reference samples were controlled at three concentration levels: low, normal, and high. Determination of the assigned value (mean ± 2SD) was performed for the following hematology analyzer series by impedance method: ABX Micros 60, Celldyn 1700, and Mindray BC 2000. Each device was sent to 10 different laboratories for evaluation. Research results for assigned values of each model (ABX Micros 60, Celldyn 1700, and Mindray BC 2000) were determined at the three concentrations. For the ABX Micros 60 and Celldyn 1700 series, 80% of laboratories had analytical results within assigned values. For the Mindray BC 2000 series, 100% of laboratories had analytical results within assigned values. The measurement results for the number of human RBCs, pseudo-leucocytes, and pseudo-platelets on each analyzer were similar between the 10 laboratories; the results of the three hematology analyzer series using the impedance method were different and the difference was statistically significant (p < 0.05). Thus, hematological reference samples for measuring the number of blood cells meeting the standards so that they can evaluate the results of laboratories using the impedance method: ABX, Celldyn 1700, Mindray BC 2000.

GABA-enriched rice bran inhibits inflammation in LPS-stimulated macrophages via suppression of TLR4-MAPK/NF-κB signaling cascades.

Gamma-aminobutyric acid (GABA)-enriched products (GEP) exhibited a wide range of pharmaceutical properties. In this study, anti-inflammatory activity of GEP from Lactobacillus fermentum-fermented water solution of rice bran was evaluated on lipopolysaccharide-activated macrophage model. GABA content in L. fermentum-fermented rice bran solution was determined up to 1.27 g/L. GEP was shown to inhibit the expression levels of inducible nitric oxide synthase and cyclooxygenase-2 enzymes. Moreover, pretreatment of GEP attenuated the generation level of interleukin (IL)-6, IL-1ß, tumor necrosis factor α, and monocyte chemoattractant protein-1. Especially, the activation of signaling pathways due to nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) was interrupted in GEP-exposed cells. Notably, molecular docking result showed a potential binding of GABA to Toll-like receptor 4 with a binding energy of -3.88 kcal/mol, suggesting the role of GABA in suppression of Toll-like receptor 4-MAPK/NF-κB signaling cascades. As the result, GEP from L. fermentum-fermented rice bran solution could be suggested as a promising food for suppression of inflammatory responses. PRACTICAL APPLICATIONS: GABA-enriched products have been evidenced to possess various pharmaceutical properties and health beneficial effects. In this study, GABA-enriched product from L. fermentum-fermented rice bran solution exhibited the inhibition on inflammatory response in macrophages. Hence, it could be used as a potential ingredient for the mitigation of inflammatory responses.

α-Glucosidase Inhibitory Cycloartanes from the Vietnamese Combretum quadrangulare.

Leaves of Combretum quadrangulare Kurz showed potent α-glucosidase inhibition. Two new cycloartane-type triterpenes, combretic acids D and E were isolated from the bioactive fraction. The chemical structures were determined using NMR and MS methods. Combretic acid D represents for the first cycloartane having a dihydrofuran ring in the side chain. Combretic acids D and E showed significant α-glucosidase inhibition, with IC50 values of 13.9 and 30.7 µM, respectively. Combretic acid D was determined to be a non-competitive type in the kinetic study. The docking study in combination with dynamic simulations of this compound provided the molecular understanding of α-glucosidase inhibition.

The role of algal fucoidans in potential anti-allergic therapeutics.

Allergic diseases are among the commonest causes of chronic ill-health and are rapidly rising the prevalence and complexity. Although the current drugs are efficacy for treatment of allergic diseases, however the extensive clinical use of these drugs has led to the diverse and undesirable side effects. Thus, the extensive studies of alternative anti-allergic agents from natural products are essential for a long-term purpose. Marine environment covers a huge source of extremely potential secondary metabolites for drug discovery. Among them, fucoidans from brown seaweeds have been evidenced to possess various biological activities and health benefit effects. Notably, a great deal of interest has been expressed regarding anti-allergic activity of fucoidans. Consequently, this contribution presents an overview of potential anti-allergic therapeutics of fucoidans from brown seaweeds to emphasize its functions in prevention as well as treatment of allergic diseases.

Natural products targeting FcεRI receptor for anti-allergic therapeutics.

Mast cells and basophils are important contributors for development of allergic reactions. The activation of these cells via cross-linking of IgE bound to FcεRI by allergen causes the generation of allergic mediators and the reaction of immediate hypersensitivity. Obviously, FcεRI is considered as a key trigger of acute allergic responses. Consequently, FcεRI is regarded as a potential target for downregulation of allergic diseases. So far, numerous synthetic agents have been reported for inhibition of FcεRI expression and FcεRI-IgE interaction. Meanwhile, natural products have received much attention due to their efficacy and safety. Recently, numerous anti-allergic agents from natural products have been revealed as promising inhibitors of allergic reactions via inhibiting the expression of FcεRI subunits as well as blocking FcεRI activation. Thus, the present contribution is mainly focused to describe natural products targeting FcεRI receptor and to emphasize their applicable potential as anti-allergic foods. PRACTICAL APPLICATIONS: Phlorotannins, epigallocatechin-3-gallate, peptides, chitooligosaccharides, and other natural products have been revealed as potential inhibitors of allergic responses. These bioactive agents target to FcεRI receptor by inhibiting expression of FcεRI and blocking interaction of FcεRI-IgE. Hence, these compounds could be applied as functional ingredients of anti-allergic foods.

The role of myricetin from Rhodomyrtus tomentosa (Aiton) Hassk fruits on downregulation of FcɛRI-mediated mast cell activation.

Rhodomyrtus tomentosa was reported to contain various bioactive metabolites, especially phenolic compounds. In the present study, the suppressive activity of phenolic compound from R. tomentosa fruits on mast cell activation was investigated in vitro. The result showed that myricetin was isolated from R. tomentosa fruits and its characterization was identified by nuclear magnetic resonance spectroscopy. Notably, myricetin was found to be effective in inhibition of mast cell degranulation by attenuating the release of ß-hexosaminidase and the elevation of intracellular calcium. Moreover, myricetin exhibited inhibitory effect on the production of IL-4 and Tumor necrosis factor alpha (TNF-α) in a concentration-dependent manner. Furthermore, high antioxidant activity of myricetin due to scavenging 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and ABTS+ radicals was also evidenced. Notably, the activation of FcɛRI-mediated signaling molecules including Syk, PLCγ, and NF-κB was also suppressed by myricetin treatment. Accordingly, myricetin from R. tomentosa fruits could be suggested as a functional food for the amelioration of allergic diseases. PRACTICAL APPLICATIONS: Polyphenol have been shown to exert various biological activities and health beneficial effects. Results from the present study revealed that myricetin from R. tomentosa fruits possesses the inhibitory effect on allergic response in mast cells. Therefore, myricetin from R. tomentosa fruits could be developed as a functional ingredient for the amelioration of allergic diseases.

An Updated Review on Pharmaceutical Properties of Gamma-Aminobutyric Acid.

Gamma-aminobutyric acid (Gaba) is a non-proteinogenic amino acid that is widely present in microorganisms, plants, and vertebrates. So far, Gaba is well known as a main inhibitory neurotransmitter in the central nervous system. Its physiological roles are related to the modulation of synaptic transmission, the promotion of neuronal development and relaxation, and the prevention of sleeplessness and depression. Besides, various pharmaceutical properties of Gaba on non-neuronal peripheral tissues and organs were also reported due to anti-hypertension, anti-diabetes, anti-cancer, antioxidant, anti-inflammation, anti-microbial, anti-allergy, hepato-protection, reno-protection, and intestinal protection. Therefore, Gaba may be considered as potential alternative therapeutics for prevention and treatment of various diseases. Accordingly, this updated review was mainly focused to describe the pharmaceutical properties of Gaba as well as emphasize its important role regarding human health.

The Role of Rhodomyrtus tomentosa (Aiton) Hassk. Fruits in Downregulation of Mast Cells-Mediated Allergic Responses.

Rhodomyrtus tomentosa, a flowering plant of Myrtaceae family from southern and southeastern Asia, was known to possess a rich source of structurally diverse and various biological activities. In this study, the inhibitory effect of R. tomentosa fruit extract (RFE) on allergic responses in calcium ionophore A23187-activated RBL-2H3 mast cells was investigated. The result showed that RFE was able to inhibit mast cell degranulation via decreasing ß-hexosaminidase release and intracellular Ca2+ elevation at the concentration of 400 µg/ml. Moreover, the suppressive effects of RFE on the production of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) were evidenced. In addition, RFE effectively scavenged DPPH radical and suppressed the reactive oxygen species generation in a dose-dependent manner. Notably, the pretreatment of RFE caused the downregulation of tyrosine kinase Fyn phospholipid enzyme phospholipase Cγ (PLCγ), extracellular-signal-regulated kinase (ERK), and nuclear factor kappa B (NF-κB) phosphorylation. These results indicated that RFE could be a promising inhibitor of allergic responses and may be developed as bioactive ingredient for prevention or treatment of allergic diseases.

Investigation of Biological Activities of Wild Bitter Melon (Momordica charantia Linn. Var. Abbreviata Ser.).

Wild bitter melon (Momordica charantia L. var. Abbreviata Ser.) is a wild edible variety of M. charantia, often used in folk medicine. In this study, the biological activities of its extract and fractions were investigated in vitro. It was found that ethyl acetate (EA) fraction exhibited high 1,1-diphenyl-2-picryl-hydrazyl (DPPH) scavenging activity with a half maximal inhibitory concentration (IC50) value of 0.43 ± 0.04 mg/mL, while the chloroform (CF), EA, and n-butanol (Bu) fractions had strong 2,2-azinobis-3-ethyl benzothiazoline-6-sulfonic acid (ABTS)+ scavenging ability with IC50 values of 0.36 ± 0.04 mg/mL, 0.35 ± 0.02 mg/mL, and 0.35 ± 0.05 mg/mL, respectively. Moreover, the EA and Bu fractions exhibited the highest protective effect against H2O2-induced DNA damage in a concentration-dependent manner. Furthermore, the EA fraction was effective in the inhibition of enzyme α-amylase activity with an IC50 value of 0.27 ± 0.029 mg/mL. Finally, it was observed that the production of nitric oxide (NO), a pro-inflammatory mediator, was significantly reduced from LPS-stimulated murine macrophage RAW 264.7 cells by the ethanol extract (ET) and the EA fraction. Therefore, wild bitter melon could be considered as a promising biomaterial for the development of pharmaceutical products.

Antiproliferative Effect of Aminoethyl-Chitooligosaccharide on Human Lung A549 Cancer Cells.

The aminoethyl-chitooligosaccharide (AE-COS) was reported to inhibit human gastric cancer cell proliferation and human fibrosarcoma cell invasion. In this study, the role of AE-COS in down-regulation of proliferation of human lung A549 cancer cells was evaluated. It was found that AE-COS was able to reduce A549 cell proliferation to (32 ± 1.3)% at a concentration of 500 µg/ml. Moreover, AE-COS treatment caused suppression on COX-2 expression in a dose-dependent manner. Notably, the role of AE-COS in induction of cell apoptosis was observed via decreasing Bcl-2 expression and increasing caspase-3 and -9 activation. Accordingly, the antiproliferative effect of AE-COS was indicated due to suppression of cell proliferation and induction of cell apoptosis, suggesting AE-COS as a promising chemotherapy agent for treatment of lung cancer.

Chemical Synthesis and Characterization of Poly(poly(ethylene glycol) methacrylate)-Grafted CdTe Nanocrystals via RAFT Polymerization for Covalent Immobilization of Adenosine.

This paper describes the functionalization of poly(poly(ethylene glycol) methacrylate) (PPEGMA)-grafted CdTe (PPEGMA-g-CdTe) quantum dots (QDs) via surface-initiated reversible addition⁻fragmentation chain transfer (SI-RAFT) polymerization for immobilization of adenosine. Initially, the hydroxyl-coated CdTe QDs, synthesized using 2-mercaptoethanol (ME) as a capping agent, were coupled with a RAFT agent, S-benzyl S'-trimethoxysilylpropyltrithiocarbonate (BTPT), through a condensation reaction. Then, 2,2'-azobisisobutyronitrile (AIBN) was used to successfully initiate in situ RAFT polymerization to generate PPEGMA-g-CdTe nanocomposites. Adenosine-above-PPEGMA-grafted CdTe (Ado-i-PPEGMA-g-CdTe) hybrids were formed by the polymer shell, which had successfully undergone bioconjugation and postfunctionalization by adenosine (as a nucleoside). Fourier transform infrared (FT-IR) spectrophotometry, energy-dispersive X-ray (EDX) spectroscopy, thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy results indicated that a robust covalent bond was created between the organic PPEGMA part, cadmium telluride (CdTe) QDs, and the adenosine conjugate. The optical properties of the PPEGMA-g-CdTe and Ado-i-PPEGMA-g-CdTe hybrids were investigated by photoluminescence (PL) spectroscopy, and the results suggest that they have a great potential for application as optimal materials in biomedicine.

The Health Beneficial Properties of Rhodomyrtus tomentosa as Potential Functional Food.

Rhodomyrtus tomentosa (Aiton) Hassk. is a flowering plant belonging to the family Myrtaceae, native to southern and southeastern Asia. It has been used in traditional Vietnamese, Chinese, and Malaysian medicine for a long time for the treatment of diarrhea, dysentery, gynecopathy, stomachache, and wound healing. Moreover, R. tomentosa is used to make various food products such as wine, tea, and jam. Notably, R. tomentosa has been known to contain structurally diverse and biologically active metabolites, thus serving as a potential resource for exploring novel functional agents. Up to now, numerous phenolic and terpenoid compounds from the leaves, root, or fruits of R. tomentosa have been identified, and their biological activities such as antioxidant, antibacterial, anti-inflammatory, and anticancer have been evidenced. In this contribution, an overview of R. tomentosa and its health beneficial properties was focused on and emphasized.

Interaction of carbohydrate binding module 20 with starch substrates.

CBM20s are starch-binding domains found in many amylolytic enzymes, including glucoamylase, alpha-amylase, beta-amylases, and a new family of starch-active polysaccharide monooxygenases (AA13 PMOs). Previous studies of CBM20-substrate interaction only concerned relatively small or soluble amylose molecules, while amylolytic enzymes often work on extended chains of insoluble starch molecules. In this study, we utilized molecular simulation techniques to gain further insights into the interaction of CBM20 with substrates of various sizes via its two separate binding sites, termed as BdS1 and BdS2. Results show that substrate binding at BdS1 involving two conserved tryptophan residues is about 2-4 kcal mol-1 stronger than that at BdS2. CBM20 exhibits about two-fold higher affinity for helical substrates than for the amylose random coils. The affinity for amylose individual double helices does not depend on the helices' length. At least three parallel double helices are required for optimal binding. The binding affinity for a substrate containing 3 or more double helices is ∼-15 kcal mol-1, which is 2-3 kcal mol-1 larger than that for individual double helices. 100 ns molecular dynamics simulations were carried out for the binding of CBM20 to an extended substrate containing 3 layers of 9 60-unit double helices (A3L). A stable conformation of CBM20-A3L was found at BdS1. However, when CBM20 binds A3L viaBdS2, it moves across the surface of the substrate and does not form a stable complex. MD simulations show that small amylose helices are quickly disrupted upon binding to CBM20. Our results provide some important molecular insights into the interactions of CBM20 with starch substrates, which will serve as the basis for further studies of CBM20-containing enzymes, including AA13 PMOs.

Spirulina maxima peptides suppress mast cell degranulation via inactivating Akt and MAPKs phosphorylation in RBL-2H3 cells.

In this study, the suppressive effects of peptides P1 (LDAVNR) and P2 (MMLDF) from enzymatic hydrolysate of Spirulina maxima on mast cell degranulation was elucidated. It was revealed that P1 and P2 exhibited significant inhibition on cell degranulation via decreasing ß-hexosaminidase release at concentration of 200 µM. Moreover, the inhibitory effects of P1 and P2 on expression and production of interleukin (IL)-13 were evidenced. Furthermore, peptide treatment caused a remarkable inhibition on the phosphorylation of Akt and mitogen-activated protein kinases (MAPKs) including ERK, p38, and JNK. Notably, the inhibitory activity of P1 on cell degranulation was found due to blockade of FcεRI receptor. Meanwhile, the inhibitory activity of P2 was involved in alleviation of intracellular reactive oxygen species (ROS) production. Collectively, peptides P1 and P2 from S. maxima were suggested to be promising inhibitors of mast cell degranulation, contributing to the development of bioactive ingredients for amelioration of allergic diseases.

The Suppressive Activity of Fucofuroeckol-A Derived from Brown Algal Ecklonia stolonifera Okamura on UVB-Induced Mast Cell Degranulation.

UV light, especially UVB, is known as a trigger of allergic reaction, leading to mast cell degranulation and histamine release. In this study, phlorotannin Fucofuroeckol-A (F-A) derived from brown algal Ecklonia stolonifera Okamura was evaluated for its protective capability against UVB-induced allergic reaction in RBL-2H3 mast cells. It was revealed that F-A significantly suppress mast cell degranulation via decreasing histamine release as well as intracellular Ca2+ elevation at the concentration of 50 µM. Moreover, the inhibitory effect of F-A on IL-1ß and TNF-α productions was also evidenced. Notably, the protective activity of F-A against mast cell degranulation was found due to scavenging ROS production. Accordingly, F-A from brown algal E. stolonifera was suggested to be promising candidate for its protective capability against UVB-induced allergic reaction.

Covalent Immobilization of Biotin on Magnetic Nanoparticles: Synthesis, Characterization, and Cytotoxicity Studies.

A simple protocol for covalent immobilization of biotin onto the surface of Fe3O4 magnetic nanoparticles (MNPs) for improving the biocompatibility of original MNPs has been realized. MNPs were first prepared by co-precipitation method which was subsequently anchored with functionalized biotin. The as-synthesized MNPs were observed to be monocrystalline as evidenced from XRD and TEM images. The covalent grafting of biotin to MNPs was confirmed by FT-IR. The XPS analysis suggested the successful preparation of Biotin-f-MNPs. The as-synthesized Biotin-f-MNPs were found to be superparamagnetic character as recorded by SQUID. Cell viability studies revealed that the biocompatibility of MNPs was improved upon Biotin immobilization.

The beneficial properties of marine polysaccharides in alleviation of allergic responses.

Marine polysaccharides have been found as the principle component in cell wall structures of seaweeds or exoskeletons of crustaceans. Due to numerous pharmaceutical properties of marine polysaccharides such as antioxidant, anti-inflammatory, antiallergic, antitumor, antiobesity, antidiabetes, anticoagulant, antiviral, immunomodulatory, cardioprotective, and antihepatopathy activities, they have been applied in many fields of biomaterials, food, cosmetic, and pharmacology. Recently, several marine polysaccharides such alginate, porphyran, fucoidan, and chitin and its derivatives have been evidenced as downregulators of allergic responses due to enhancement of innate immune system, alteration of Th1/Th2 balance forward to Th1 cells, inhibition of IgE production, and suppression of mast cell degranulation. This contribution, therefore, focuses on antiallergic properties of marine polysaccharides and emphasizes their potential application as bioactive food ingredients as well as nutraceuticals for prevention of allergic disorders.

Angiotensin-I converting enzyme inhibitory peptides from antihypertensive skate (Okamejei kenojei) skin gelatin hydrolysate in spontaneously hypertensive rats.

The aim of this study was to investigate antihypertensive effect of bioactive peptides from skate (Okamejei kenojei) skin gelatin. The Alcalase/protease gelatin hydrolysate below 1 kDa (SAP) exhibited the highest angiotensin-I converting enzyme (ACE) inhibition compared to other hydrolysates. SAP can decrease systolic blood pressure significantly in spontaneously hypertensive rats. SAP inhibited vasoconstriction via PPAR-γ expression, activation and phosphorylation of eNOS in lungs. Moreover, the expression levels of endothelin-1, RhoA, α-smooth muscle actin, cleaved caspase 3 and MAPK were decreased by SAP in lungs. Vascularity, muscularization and cellular proliferation in lungs were detected by immunohistochemical staining. Finally, two purified peptides (LGPLGHQ, 720Da and MVGSAPGVL, 829Da) showed potent ACE inhibition with IC50 values of 4.22 and 3.09 µM, respectively. These results indicate that bioactive peptides isolated from skate skin gelatin may serve as candidates against hypertension and could be used as functional food ingredients.

Marine-derived polysaccharides for regulation of allergic responses.

Polysaccharides are macromolecules made up of many monosaccharides joined together by glycosidic bonds. Polysaccharides from marine sources are widely distributed as the principle component in cell wall structures of seaweeds or exoskeletons of crustaceans. So far, marine polysaccharides have been used in many fields of biomaterials, food, cosmetic, and pharmacology. Especially, numerous pharmaceutical properties of marine polysaccharides have been revealed such as antioxidant, anti-inflammatory, antiallergic, antitumor, antiobesity, antidiabetes, anticoagulant, antiviral, immunomodulatory, cardioprotective, antihepatopathy, antiuropathy, and antirenalpathy activities. Recently, several marine polysaccharides such alginate, porphyran, fucoidan, and chitin and its derivatives have been found as modulators of allergic responses due to enhancing innate immune system, altering Th1/Th2 balance, inhibiting IgE production, and suppressing mast cell degranulation. This contribution, therefore, focuses specially on the immunomodulatory effect of marine polysaccharides and emphasizes their potential application as candidates of pharmaceuticals as well as nutraceuticals to prevent allergic disorders.