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 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.

Covalently Functionalized Graphene with Molecularly Imprinted Polymers for Selective Adsorption and Electrochemical Detection of Chloramphenicol.

In this report, we have presented a novel route to attach molecularly imprinted polymers (MIPs) on the surface of reduced graphene oxide (rGO) through covalent bonding. First, the surface of rGO was modified with maleic anhydride (MA) via a Diels-Alder reaction using a deep eutectic solvent (DES). Next, 3-propyl-1-vinylimidazolium molecular units were anchored and polymerized in the presence of ethylene glycol dimethacrylate (EGDMA) using chloramphenicol (CAP) as the template. Primarily, we investigated the effect of the molar ratio of individual precursors on the adsorption capacity of synthesized materials and accordingly fabricated the electrochemical sensor for CAP detection. Electrochemical results evidenced that the covalent bonding of MIP units enhanced the sensitivity of the respective sensor toward CAP in water as well as in real honey samples with high selectivity, stability, and reproducibility. This synthesis strategy involves the covalent binding of MIP on rGO materials via click chemisty under sonication power excluding harmful solvents and energy-intensive processes and thus could be a motivation for developing future electrochemical sensors through similar "green" routes.

Protective effect of chitin oligosaccharides against lipopolysaccharide-induced inflammatory response in BV-2 microglia.

Chitin oligosaccharides (NA-COS) of two different molecular weight ranges (below 1 and 1-3 kDa) were examined for their capabilities against lipopolysaccharide-induced inflammatory responses in BV-2 murine microglia. It was found that NA-COS reduced the level of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production by suppressing the expression of NO synthase (iNOS) and cyclooxygenase (COX)-2 without significant cytotoxicity. Furthermore, the inhibitory effects of NA-COS on generation of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α were determined. Notably, NA-COS exerted anti-inflammatory activities via blocking degradation of inhibitor of kappaB-alpha (IκB-α), translocation of nuclear factor (NF)-κB, and phosphorylation of mitogen-activated protein kinases (MAPKs) in a dose-dependent manner. These findings provide mechanistic insights into the anti-inflammatory and neuroprotective actions of NA-COS in BV-2 microglia.

Click-Chemistry-Mediated Synthesis of Silver Nanoparticle-Supported Polymer-Wrapped Carbon Nanotubes: Glucose Sensor and Antibacterial Material.

We report a novel approach for the synthesis of silver nanoparticles (NPs) stabilized on polymer-wrapped carbon nanotubes (Ag@polymer/CNTs) for the non-enzymatic glucose sensing and antibacterial activity applications. Poly(styrene-alt-maleic anhydride) (PSM) was functionalized with amino furan to obtain furan-modified poly(styrene-alt-maleic anhydride) (PSMF), which was later grafted onto the surface of CNTs by Diels-Alder "click" reaction to afford a polymer/CNTs hybrid material. The photo-deposition technique was applied to immobilized small-sized (∼10 nm) AgNPs on the surface of the polymer/CNTs hybrid material using visible light irradiation. The resulting material, Ag@polymer/CNTs, showed promising electrocatalytic activity for the non-enzymatic glucose sensing and antibacterial activity in vitro assays toward Escherichia coli, Staphylococcus aureus, and Bacillus cereus bacteria strains. Covalent-bonded polymer layer-bearing carboxylic pendent groups to the CNTs might be playing a pivot role in not only stabilizing AgNPs but also facile electron-transfer reaction, thus demonstrating better activity.

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.

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.

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.

Draft genome sequence data of Rhodosporidium toruloides VN1, a strain capable of producing natural astaxanthin.

Rhodosporidium toruloides strain VN1 is of special interest because of its capability for high astaxanthin production. Here, we report the draft genome sequence of R. toruloides VN1, which comprises 20.01 Mb in 424 contigs with an overall G + C content of 61.8%. This whole-genome shotgun project has been deposited at DDBJ/EMBL/GenBank under the accession number SJTE00000000.

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.

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.

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.

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.

4-hydroxybenzaldehyde-chitooligomers suppresses H2O2-induced oxidative damage in microglia BV-2 cells.

Positive charges of chitooligomer (COS) enable COS to interact with negatively charged anionic groups on the cell surface resulting in an improvement in the biological activity of COS and its derivatives. In this study, 4-hydroxybenzaldehyde-COS (HB-COS) was synthesized and investigated for its abilities against H2O2-induced oxidative stress in microglia BV-2 cells. Under oxidative stress, HB-COS significantly attenuated reactive oxygen species (ROS) generation and DNA oxidation, and upregulated the protein levels of antioxidative enzymes. HB-COS is therefore proposed as a potential protective agent against neuronal damage.

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.

Antioxidant effects of chitin, chitosan, and their derivatives.

Chitin, chitosan, and their derivatives are considered to promote diverse activities, including antioxidant, antihypertensive, anti-inflammatory, anticoagulant, antitumor and anticancer, antimicrobial, hypocholesterolemic, and antidiabetic effects, one of the most crucial of which is the antioxidant effect. By modulating and improving physiological functions, chitin, chitosan, and their derivatives may provide novel therapeutic applications for the prevention or treatment of chronic diseases. Antioxidant activity of chitin, chitosan, and their derivatives can be attributed to in vitro and in vivo free radical-scavenging activities. Antioxidant effect of chitin, chitosan, and their derivatives may be used as functional ingredients in food formulations to promote consumer health and to improve the shelf life of food products. This chapter presents an overview of the antioxidant activity of chitin, chitosan, and their derivatives with the potential utilization in the food and pharmaceutical industries.

Active peptides from skate (Okamejei kenojei) skin gelatin diminish angiotensin-I converting enzyme activity and intracellular free radical-mediated oxidation.

Skin gelatin of skate (Okamejei kenojei) was hydrolyzed using Alcalase, flavourzyme, Neutrase and protamex. It was found that the Alcalase hydrolysate exhibited the highest angiotensin-I converting enzyme (ACE) inhibitory activity. Then, Alcalase hydrolysate was further hydrolyzed with protease and separated by an ultrafiltration membrane system. Finally, two peptides responsible for ACE inhibitory activity were identified to be MVGSAPGVL (829Da) and LGPLGHQ (720Da), with IC50 values of 3.09 and 4.22µM, respectively. Moreover, the free radical-scavenging activity of the purified peptides was determined in human endothelial cells. In addition, the antioxidative mechanism of the purified peptides was evaluated by protein and gene expression levels of antioxidant enzymes. The current study demonstrated that the peptides derived from skate skin gelatin could be used in the food industry as functional ingredients with potent antihypertensive and antioxidant benefits.

The role of peptides derived from Spirulina maxima in downregulation of FcεRI-mediated allergic responses.

SCOPE: Spirulina has been found suitable for use as a bioactive additive. It is an excellent source of protein that can be hydrolyzed into bioactive peptides. Two peptides LDAVNR (P1) and MMLDF (P2) purified from enzymatic hydrolysate of Spirulina maxima have been reported to be effective against early atherosclerotic responses. In this study, the intracellular mechanism involved in the downregulation of these peptides on high-affinity IgE receptor-mediated allergic reaction was further investigated. METHODS AND RESULTS: RBL-2H3 mast cells were pretreated with P1 or P2 and sensitized with dinitrophenyl-specific IgE antibody before stimulation of antigen dinitrophenyl-BSA. It was revealed that P1 and P2 exhibited significant inhibition on mast-cell degranulation via decreasing histamine release and intracellular Ca(2+) elevation. The inhibitory activity of P1 was found due to blockade of calcium- and microtubule-dependent signaling pathways. Meanwhile, the inhibition of P2 was involved in suppression of phospholipase Cγ activation and reactive oxygen species production. Moreover, the suppressive effects of P1 and P2 on generation of IL-4 were evidenced via depression of nuclear factor-κB translocation. CONCLUSION: These findings indicate that peptides P1 and P2 from S. maxima may be promising candidates of antiallergic therapeutics, contributing to development of bioactive food ingredients for amelioration of allergic diseases.

Protection of 4-hydroxybenzyl-chitooligomers against inflammatory responses in Chang liver cells.

The aim of this study was to investigate anti-inflammatory activity of 4-hydroxybenzyl-chitooligomers (HB-COS) in Chang liver cells stimulated by a cytokine mixture. It was revealed that HB-COS decreased the level of nitric oxide and prostaglandin E2 (PGE2) production by diminishing the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) without significant cytotoxicity. Moreover, HB-COS exerted inhibitory effects on the production of pro-inflammatory mediator (interleukin-6) in Chang liver cells. Notably, HB-COS exhibited anti-inflammatory activities via blocking degradation of inhibitory kappa B alpha (IκB-α), translocation of nuclear factor kappa B (NF-κB), and phosphorylation of mitogen-activated protein kinases (MAPKs) in a dose-dependent manner. Collectively, these findings indicated that HB-COS possessed potential anti-inflammatory effects in Chang liver cells, and could be a useful therapeutic agent for the treatment of hepatic inflammatory diseases.