Engineering homoeologs provide a fine scale for quantitative traits in polyploid.

Numerous staple crops exhibit polyploidy and are difficult to genetically modify. However, recent advances in genome sequencing and editing have enabled polyploid genome engineering. The hexaploid black nightshade species Solanum nigrum has immense potential as a beneficial food supplement. We assembled its genome at the scaffold level. After functional annotations, we identified homoeologous gene sets, with similar sequence and expression profiles, based on comparative analyses of orthologous genes with close diploid relatives Solanum americanum and S. lycopersicum. Using CRISPR-Cas9-mediated mutagenesis, we generated various mutation combinations in homoeologous genes. Multiple mutants showed quantitative phenotypic changes based on the genotype, resulting in a broad-spectrum effect on the quantitative traits of hexaploid S. nigrum. Furthermore, we successfully improved the fruit productivity of Boranong, an orphan cultivar of S. nigrum suggesting that engineering homoeologous genes could be useful for agricultural improvement of polyploid crops.

Characterization of Pseudomonas sp. NIBR-H-19, an Antimicrobial Secondary Metabolite Producer Isolated from the Gut of Korean Native Sea Roach, Ligia exotica.

The need to discover new types of antimicrobial agents has grown since the emergence of antibiotic-resistant pathogens that threaten human health. The world's oceans, comprising complex niches of biodiversity, are a promising environment from which to extract new antibiotics-like compounds. In this study, we newly isolated Pseudomonas sp. NIBR-H-19 from the gut of the sea roach Ligia exotica and present both phenotypes and genomic information consisting of 6,184,379 bp in a single chromosome possessing a total of 5,644 protein-coding genes. Genomic analysis of the isolated species revealed that numerous genes involved in antimicrobial secondary metabolites are predicted throughout the whole genome. Moreover, our analysis showed that among twenty-five pathogenic bacteria, the growth of three pathogens, including Staphylococcus aureus, Streptococcus hominis and Rhodococcus equi, was significantly inhibited by the culture of Pseudomonas sp. NIBR-H-19. The characterization of marine microorganisms with biochemical assays and genomics tools will help uncover the biosynthesis and action mechanism of antimicrobial metabolites for development as antagonistic probiotics against fish pathogens in an aquatic culture system.

Dynamics of the Gut Microbiome and Transcriptome in Korea Native Ricefish (Oryzias latipes) during Chronic Antibiotic Exposure.

Antibiotics have been widely used to inhibit microbial growth and to control bacterial infection; however, they can trigger an imbalance in the gut flora of the host and dysregulate the host gene regulatory system when discharged into the aquatic environment. We investigated the effects of chronic exposure to a low concentration of erythromycin and ampicillin, focusing on gut microbiome and global gene expression profiles from Korea native ricefish (Oryzias latipes). The proportion of Proteobacteria (especially the opportunistic pathogen Aeromonas veronii) was significantly increased in the ricefish under the chronic exposure to erythromycin and ampicillin, whereas that of other bacterial phyla (i.e., Fusobacteria) decreased. In addition, the expression of genes involved in immune responses such as chemokines and immunocyte chemotaxis was significantly influenced in ricefish in the aquatic environment with antibiotics present. These results show that the internal microbial flora and the host gene expression are susceptible even at a low concentration of chronic antibiotics in the environment, supporting the importance of the appropriate use of antibiotic dose to maintain the sustainable and healthy aquaculture industry and water ecosystem.

The comparisons of expression pattern reveal molecular regulation of fruit metabolites in S. nigrum and S. lycopersicum.

Solanum nigrum, known as black nightshade, is a medicinal plant that contains many beneficial metabolites in its fruit. The molecular mechanisms underlying the synthesis of these metabolites remain uninvestigated due to limited genetic information. Here, we identified 47,470 unigenes of S. nigrum from three different tissues by de novo transcriptome assembly, and 78.4% of these genes were functionally annotated. Moreover, gene ontology (GO) analysis using 18,860 differentially expressed genes (DEGs) revealed tissue-specific gene expression regulation. We compared gene expression patterns between S. nigrum and tomato (S. lycopersicum) in three tissue types. The expression patterns of carotenoid biosynthetic genes were different between the two species. Comparison of the expression patterns of flavonoid biosynthetic genes showed that 9 out of 14 enzyme-coding genes were highly upregulated in the fruit of S. nigrum. Using CRISPR-Cas9-mediated gene editing, we knocked out the R2R3-MYB transcription factor SnAN2 gene, an ortholog of S. lycopersicum ANTHOCYANIN 2. The mutants showed yellow/green fruits, suggesting that SnAN2 plays a major role in anthocyanin synthesis in S. nigrum. This study revealed the connection between gene expression regulation and corresponding phenotypic differences through comparative analysis between two closely related species and provided genetic resources for S. nigrum.

Production of juvenile masu salmon (Oncorhynchus masou) from spermatogonia-derived sperm and oogonia-derived eggs via intraperitoneal transplantation of immature germ cells.

No effective cryopreservation technique exists for fish eggs and embryos; thus, the cryopreservation of germ cells (spermatogonia or oogonia) and subsequent generation of eggs and sperm would be an alternative solution for the long-term preservation of piscine genetic resources. Nevertheless, in our previous study using rainbow trout, we showed that recipients transplanted with XY spermatogonia or XX oogonia produced unnatural sex-biased F1 offspring. To overcome these obstacles, we transplanted immature germ cells (XX oogonia or XY spermatogonia; frozen for 33 days) into the body cavities of triploid hatchlings, and the transplanted germ cells possessed a high capacity for differentiating into eggs and sperm in the ovaries and testes of recipients. Approximately 30% of triploid recipients receiving frozen germ cells generated normal salmon that displayed the donor-derived black body color phenotype, although all triploid salmon not receiving transplants were functionally sterile. Furthermore, F1 offspring obtained from insemination of the oogonia-derived eggs and spermatogonia-derived sperm show a normal sex ratio of 1:1 (female:male). Thus, this method presented a critical technique for practical conservation projects for other teleost fish species and masu salmon.

UVC light modulates vitamin C and phenolic biosynthesis in acerola fruit: role of increased mitochondria activity and ROS production.

The effects of ultraviolet-C light (UVC) on vitamin C and phenolic compounds in acerola during postharvest storage were investigated in order to elucidate the mechanism inducing the antioxidant systems. The fruits, stored at 10 °C for 7 days after a hormetic UVC irradiation (two pulses of 0.3 J/cm2), showed significantly less degradation of vitamin C and phenolic compounds than the control without the UVC challenge. UVC activated the L-galactono-1,4-lactone dehydrogenase (GalDH), a key enzyme for vitamin C biosynthesis, and altered the composition of phenolic compounds, through phenolic biosynthesis, in acerola during postharvest storage. UVC also induced reactive oxygen species (ROS) productions at immediate (day 0) and late (day 7) times during postharvest storage through the mitochondrial electron transport chain and NADPH oxidase, respectively. Results suggest that UVC helps in the retention of vitamin C and phenolic content in acerola by altering ascorbic acid and phenolic metabolism through an increase in mitochondrial activity and a ROS-mediated mechanism. Data showed the beneficial effects of UVC on maintenance of nutraceutical quality in acerola during postharvest storage and supplied new insights into understanding the mechanism by which UVC irradiation enhance the antioxidant system in fruits.

Potential of Cell-Free Supernatant from Lactobacillus plantarum NIBR97, Including Novel Bacteriocins, as a Natural Alternative to Chemical Disinfectants.

The recent pandemic of coronavirus disease 2019 (COVID-19) has increased demand for chemical disinfectants, which can be potentially hazardous to users. Here, we suggest that the cell-free supernatant from Lactobacillus plantarum NIBR97, including novel bacteriocins, has potential as a natural alternative to chemical disinfectants. It exhibits significant antibacterial activities against a broad range of pathogens, and was observed by scanning electron microscopy (SEM) to cause cellular lysis through pore formation in bacterial membranes, implying that its antibacterial activity may be mediated by peptides or proteins and supported by proteinase K treatment. It also showed significant antiviral activities against HIV-based lentivirus and influenza A/H3N2, causing lentiviral lysis through envelope collapse. Furthermore, whole-genome sequencing revealed that NIBR97 has diverse antimicrobial peptides, and among them are five novel bacteriocins, designated as plantaricin 1 to 5. Plantaricin 3 and 5 in particular showed both antibacterial and antiviral activities. SEM revealed that plantaricin 3 causes direct damage to both bacterial membranes and viral envelopes, while plantaricin 5 damaged only bacterial membranes, implying different antiviral mechanisms. Our data suggest that the cell-free supernatant from L. plantarum NIBR97, including novel bacteriocins, is potentially useful as a natural alternative to chemical disinfectants.

Potential of Bacteriocins from Lactobacillus taiwanensis for Producing Bacterial Ghosts as a Next Generation Vaccine.

Bacteriocins are functionally diverse toxins produced by most microbes and are potent antimicrobial peptides (AMPs) for bacterial ghosts as next generation vaccines. Here, we first report that the AMPs secreted from Lactobacillus taiwanensis effectively form ghosts of pathogenic bacteria and are identified as diverse bacteriocins, including novel ones. In detail, a cell-free supernatant from L. taiwanensis exhibited antimicrobial activities against pathogenic bacteria and was observed to effectively cause cellular lysis through pore formation in the bacterial membrane using scanning electron microscopy (SEM). The treatment of the cell-free supernatant with proteinase K or EDTA proved that the antimicrobial activity is mediated by AMPs, and the purification of AMPs using Sep-Pak columns indicated that the cell-free supernatant includes various amphipathic peptides responsible for the antimicrobial activity. Furthermore, the whole-genome sequencing of L. taiwanensis revealed that the strain has diverse bacteriocins, confirmed experimentally to function as AMPs, and among them are three novel bacteriocins, designated as Tan 1, Tan 2, and Tan 3. We also confirmed, using SEM, that Tan 2 effectively produces bacterial ghosts. Therefore, our data suggest that the bacteriocins from L. taiwanensis are potentially useful as a critical component for the preparation of bacterial ghosts.

Antibacterial and Anti-Inflammatory Effects of Novel Peptide Toxin from the Spider Pardosa astrigera.

The prevalence of antibiotic-resistant bacteria has become an immediate threat to public health. Antimicrobial peptides are attracting attention as a new source of antibiotics due to their ability to prevent drug-resistances with fewer side effects. Spider venom is composed of various bioactive substances with multiple functionalities such as antimicrobial and anti-inflammatory effects. Here, RNA sequencing was conducted on the venom gland of the spider Pardosa astrigera, and a potential toxin peptide with antibacterial properties was selected via homology and in silico analysis. A novel toxin, Lycotoxin-Pa4a, inhibited both gram-negative and gram-positive bacteria by disrupting the outer and bacterial cytoplasmic membrane. Moreover, the peptide downregulated the expression of pro-inflammatory mediators while upregulating the level of anti-inflammatory cytokine by inactivating mitogen-activated protein kinase signaling in a lipopolysaccharide-stimulated murine macrophage cell line. In this research, we identified a novel peptide toxin, Lycotoxin-pa4a, with antibacterial and anti-inflammatory properties, suggesting its potential for the development of a new antibiotics, as well as offering insights into the utilization of biological resources.

In vitro Edwardsiella piscicida CK108 Transcriptome Profiles with Subinhibitory Concentrations of Phenol and Formalin Reveal New Insights into Bacterial Pathogenesis Mechanisms.

Phenol and formalin are major water pollutants that are frequently discharged into the aquatic milieu. These chemicals can affect broad domains of life, including microorganisms. Aquatic pollutants, unlike terrestrial pollutants, are easily diluted in water environments and exist at a sub-inhibitory concentration (sub-IC), thus not directly inhibiting bacterial growth. However, they can modulate gene expression profiles. The sub-IC values of phenol and formalin were measured by minimal inhibitory concentration (MIC) assay to be 0.146% (1.3 mM) and 0.0039% (0.38 mM), respectively, in Edwardsiella piscicida CK108, a Gram-negative fish pathogen. We investigated the differentially expressed genes (DEG) by RNA-seq when the cells were exposed to the sub-ICs of phenol and formalin. DEG analyses revealed that genes involved in major virulence factors (type I fimbriae, flagella, type III and type VI secretion system) and various cellular pathways (energy production, amino acid synthesis, carbohydrate metabolism and two-component regulatory systems) were up- or downregulated by both chemicals. The genome-wide gene expression data corresponded to the results of a quantitative reverse complementary-PCR and motility assay. This study not only provides insight into how a representative fish pathogen, E. piscicida CK108, responds to the sub-ICs of phenol and formalin but also shows the importance of controlling chemical pollutants in aquatic environments.

Functional Chemical Components in Protaetia brevitarsis Larvae: Impact of Supplementary Feeds.

The goal of this study was to evaluate the influence of various supplementary feeds on the chemical composition and production of bioactive substances in Protaetia brevitarsis larvae. The primary feed-oak-fermented sawdust-was supplemented with a variety of substances, including aloe, apple, banana, sweet persimmon (S. persimmon) and sweet pumpkin (S. pumpkin). Crude protein and fat content were the highest in the control and S. pumpkin group, respectively. Supplementary feeds increased the content of unsaturated fatty acids, except in the group receiving S. pumpkin, in which oleic acid was the most abundant (58.2%-64.5%). Free essential amino acids in larvae receiving supplementary aloe were higher compared with the control group except for Lys and His. Polyphenol and flavonoid contents and the antioxidant activities of ABTS and DPPH were higher in all treated groups compared with the control group. Although supplementary feeds led to a decreased crude protein content in the treated larvae when compared with the control group, these treatments generally improved the levels of unsaturated fatty acids and antioxidative activity. Therefore, we suggest that among the supplementary foods tested, aloe is a better resource for P. brevitarsis based on crude protein content, free amino acids and other bioactive compounds such as unsaturated fatty acids and antioxidants.

Draft Genome Sequence of a Fish Pathogen, Edwardsiella piscicida Isolate CK41.

Edwardsiella piscicida CK41 is a fish-pathogenic Gram-negative bacterium isolated from diseased flounder in the Republic of Korea. Here, we report the genome sequence of E. piscicida CK41, comprising one chromosome of 3.76 Mbp and one plasmid of 72.7 kbp. A total of 3,406 protein-coding genes, 98 tRNAs, and 25 rRNAs are predicted to be present in the genome.

Alpha-tocopherol exerts protective function against the mucotoxicity of particulate matter in amphibian and human goblet cells.

Exposure to particulate matter (PM) in ambient air is known to increase the risk of cardiovascular disorders and mortality. The cytotoxicity of PM is mainly due to the abnormal increase of reactive oxygen species (ROS), which damage cellular components such as DNA, RNA, and proteins. The correlation between PM exposure and human disorders, including mortality, is based on long-term exposure. In this study we have investigated acute responses of mucus-secreting goblet cells upon exposure to PM derived from a heavy diesel engine. To this end, we employed the mucociliary epithelium of amphibian embryos and human Calu-3 cells to examine PM mucotoxicity. Our data suggest that acute exposure to PM significantly impairs mucus secretion and results in the accumulation of mucus vesicles in the cytoplasm of goblet cells. RNA-seq analysis revealed that acute responses to PM exposure significantly altered gene expression patterns; however, known regulators of mucus production and the secretory pathway were not significantly altered. Interestingly, pretreatment with α-tocopherol nearly recovered the hyposecretion of mucus from both amphibian and human goblet cells. We believe this study demonstrates the mucotoxicity of PM and the protective function of α-tocopherol on mucotoxicity caused by acute PM exposure from heavy diesel engines.

Ellagic Acid and Urolithins A and B Differentially Regulate Fat Accumulation and Inflammation in 3T3-L1 Adipocytes While Not Affecting Adipogenesis and Insulin Sensitivity.

Ellagic acid (EA) is a component of ellagitannins, present in crops such as pecans, walnuts, and many berries, which metabolized by the gut microbiota forms urolithins A, B, C, or D. In this study, ellagic acid, as well as urolithins A and B, were tested on 3T3-L1 preadipocytes for differentiation and lipid accumulation. In addition, inflammation was studied in mature adipocytes challenged with lipopolysaccharide (LPS). Results indicated that EA and urolithins A and B did not affect differentiation (adipogenesis) and only EA and urolithin A attenuated lipid accumulation (lipogenesis), which seemed to be through gene regulation of glucose transporter type 4 (GLUT4) and adiponectin. On the other hand, gene expression of cytokines and proteins associated with the inflammation process indicate that urolithins and EA differentially inhibit tumor necrosis factor alpha (TNFα), inducible nitric oxide synthase (iNOS), interleukin 6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). Urolithins A and B were found to reduce nuclear levels of phosphorylated nuclear factor κB (p-NF-κB), whereas all treatments showed expression of nuclear phosphorylated protein kinase B (p-AKT) in challenged LPS cells when treated with insulin, indicating the fact that adipocytes remained insulin sensitive. In general, urolithin A is a compound able to reduce lipid accumulation, without affecting the protein expression of peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer binding protein-α (c/EBPα), and PPARα, whereas EA and urolithin B were found to enhance PPARγ and c/EBPα protein expressions as well as fatty acid (FA) oxidation, and differentially affected lipid accumulation.

Characterization of Venom Components and Their Phylogenetic Properties in Some Aculeate Bumblebees and Wasps.

: To identify and compare venom components and expression patterns, venom gland-specific transcriptome analyses were conducted for 14 Aculeate bees and wasps. TPM (transcripts per kilobase million) values were normalized using the average transcription level of a reference housekeeping gene (dimethyladenosine transferase). Orthologous venom component genes across the 14 bee and wasp species were identified, and their relative abundance in each species was determined by comparing normalized TPM values. Based on signal sequences in the transcripts, the genes of novel venom components were identified and characterized to encode potential allergens. Most of the allergens and pain-producing factors (arginine kinase, hyaluronidase, mastoparan, phospholipase A1, phospholipase A2, and venom allergen 5) showed extremely high expression levels in social wasps. Acid phosphatase, neprilysin, and tachykinin, which are known allergens and neurotoxic peptides, were found in the venom glands of solitary wasps more often than in social wasps. In the venom glands of bumblebees, few or no transcripts of major allergens or pain-producing factors were identified. Taken together, these results indicate that differential expression patterns of the venom genes in some Aculeate species imply that some wasps and bumblebee species have unique groups of highly expressed venom components. Some venom components reflected the Aculeate species phylogeny, but others did not. This unique evolution of specific venom components in different groups of some wasps and bumblebee species might have been shaped in response to both ecological and behavioral influences.

Solving the controversy of healthier organic fruit: Leaf wounding triggers distant gene expression response of polyphenol biosynthesis in strawberry fruit (Fragaria x ananassa).

The claim that organic agriculture produces higher levels of phytochemicals has been controversial for decades. Using strawberries as a model crop in field conditions, a preharvest leaf wounding stress was applied to study the production of phytochemicals in fruits. As a result phenolic compounds (PCs) and total soluble sugars increased significantly, where specific phenylpropanoids showed increment up to 137% and several genes related to PCs biosynthesis and sugar transport were overexpressed. It was observed that the accumulation of PCs on fruits can be triggered by the application of wounding stress in a distant tissue and this accumulation is directly related to carbon partition and associated gene expression. This supports the idea that higher levels of healthy phytochemicals reported in organic fruits and vegetables could be due to the wounding component of the biotic stress attributed to insects to which the plant are exposed to.

Heterochiral Assembly of Amphiphilic Peptides Inside the Mitochondria for Supramolecular Cancer Therapeutics.

Self-assembly of peptides containing both l- and d-isomers often results in nanostructures with enhanced properties compared to their enantiomeric analogues, such as faster kinetics of formation, higher mechanical strength, and enzymatic stability. However, occurrence and consequences of the heterochiral assembly in the cellular microenvironment are unknown. In this study, we monitored heterochiral assembly of amphiphilic peptides inside the cell, specifically mitochondria of cancer cells, resulting in nanostructures with refined morphological and biological properties owing to the superior interaction between the backbones of opposite chirality. We have designed a mitochondria penetrating tripeptide containing a diphenyl alanine building unit, named as Mito-FF due to their mitochondria targeting ability. The short peptide amphiphile, Mito-FF co-assembled with its mirror pair, Mito-ff, induced superfibrils of around 100 nm in diameter and 0.5-1 µm in length, while enantiomers formed only narrow fibers of 10 nm in diameter. The co-administration of Mito-FF and Mito-ff in the cell induced drastic mitochondrial disruption both in vitro and in vivo. The experimental and theoretical analyses revealed that pyrene capping played a major role in inducing superfibril morphology upon the co-assembly of racemic peptides. This work shows the impact of chirality control over the peptide self-assembly inside the biological system, thus showing a potent strategy for fabricating promising peptide biomaterials by considering chirality as a design modality.

Photo-crosslinkable elastomeric protein-derived supramolecular peptide hydrogel with controlled therapeutic CO-release.

As an attempt to establish a method for efficient and safe administration of therapeutic carbon monoxide (CO) to the human body, supramolecular nanoplatforms incorporated with CO-releasing molecules (CORMs) have recently been developed. In particular, hydrogel scaffolds have attracted considerable attention due to the possibility of site-specific and controlled liberation of CO. However, it would be greatly beneficial to enhance the mechanical strength of hydrogels to widen their applicability in biomedical, pharmaceutical, and surgical sectors. Herein, we report a visible light-mediated crosslinkable supramolecular CO-releasing hydrogel (CORH), based on the fibrillar assembly of elastomeric protein-derived tyrosine-containing short peptides. A photo-driven dimerization of tyrosine moieties located on the fibrillar surface of CORH, accelerated by a Ru-based catalyst, results in the entanglement and bundling of nanofibrils that significantly increases the mechanical strength and stability of the CORH, which allows prolonged CO-liberation through limiting the contact of CORMs with water molecules. The contact probability of a CORM with water determined by the spatial position of the CORM on the fibrils containing a crosslinkable tyrosine moiety that affects CO-releasing behavior was confirmed by adjusting the CORM position closer to or farther from the tyrosine in the peptide sequence. A bulky CORM closely located to the tyrosine in a peptide inhibited the effective dityrosine formation of tyrosine on the fibril surface, resulting in loose bundling of nanofibrils in the CORH and facilitating the release of CO through the exchange with water. The photo-crosslinked CORH demonstrated a potent cytoprotective effect on oxidatively stressed cardiomyocytes, as expected. This work could provide a useful insight for the practical application of gasotransmitters as functional nanomaterials in pharmaceutical and biomedical fields.

Carpinus turczaninowii extract modulates arterial inflammatory response: a potential therapeutic use for atherosclerosis.

BACKGROUND/OBJECTIVES: Vascular inflammation is an important feature in the atherosclerotic process. Recent studies report that leaves and branches of Carpinus turczaninowii (C. turczaninowii) have antioxidant capacity and exert anti-inflammatory effects. However, no study has reported the regulatory effect of C. turczaninowii extract on the arterial inflammatory response. This study therefore investigated modulation of the arterial inflammatory response after exposure to C. turczaninowii extract, using human aortic vascular smooth muscle cells (HAoSMCs). MATERIALS/METHODS: Scavenging activity of free radicals, total phenolic content (TPC), cell viability, mRNA expressions, and secreted levels of cytokines were measured in LPS-stimulated (10 ng/mL) HAoSMCs treated with the C. turczaninowii extract. RESULTS: C. turczaninowii extract contains high amounts of TPC (225.6 ± 21.0 mg of gallic acid equivalents/g of the extract), as well as exerts time-and dose-dependent increases in strongly scavenged free radicals (average 14.8 ± 1.97 µg/mL IC50 at 40 min). Cell viabilities after exposure to the extracts (1 and 10 µg/mL) were similar to the viability of non-treated cells. Cytokine mRNA expressions were significantly suppressed by the extracts (1 and 10 µg/mL) at 6 hours (h) after exposure. Interleukin-6 secretion was dose-dependently suppressed 2 h after incubation with the extract, at 1-10 µg/mL in non-stimulated cells, and at 5 and 10 µg/mL in LPS-stimulated cells. Similar patterns were also observed at 24 h after incubation with the extract (at 1-10 µg/mL in non-stimulated cells, and at 10 µg/mL in the LPS-stimulated cells). Soluble intracellular vascular adhesion molecules (sICAM-1) secreted from non-stimulated cells and LPS-stimulated cells were similarly suppressed in a dose-dependent manner after 24 h exposure to the extracts, but not after 2 h. In addition, sICAM-1 concentration after 24 h treatment was positively related to IL-6 levels after 2 h and 24 h exposure (r = 0.418, P = 0.003, and r = 0.524, P < 0.001, respectively). CONCLUSIONS: This study demonstrates that C. turczaninowii modulates the arterial inflammatory response, and indicates the potential to be applied as a therapeutic use for atherosclerosis.

Carpinus turczaninowii Extract May Alleviate High Glucose-Induced Arterial Damage and Inflammation.

Hyperglycemia-induced oxidative stress triggers severe vascular damage and induces an inflammatory vascular state, and is, therefore, one of the main causes of atherosclerosis. Recently, interest in the natural compound Carpinus turczaninowii has increased because of its reported antioxidant and anti-inflammatory properties. We investigated whether a C. turczaninowii extract was capable of attenuating high glucose-induced inflammation and arterial damage using human aortic vascular smooth muscle cells (hASMCs). mRNA expression levels of proinflammatory response [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)], endoplasmic reticulum (ER) stress [CCAAT-enhancer-binding proteins (C/EBP) homologous protein (CHOP)], and adenosine monophosphate (AMP)-protein activated kinase α2 (AMPK α2)], and DNA damage [phosphorylated H2.AX (p-H2.AX)] were measured in hASMCs treated with the C. turczaninowii extracts (1 and 10 µg/mL) after being stimulated by high glucose (25 mM) or not. The C. turczaninowii extract attenuated the increased mRNA expression of IL-6, TNF-α, and CHOP in hASMCs under high glucose conditions. The expression levels of p-H2.AX and AMPK α2 induced by high glucose were also significantly decreased in response to treatment with the C. turczaninowii extract. In addition, 15 types of phenolic compounds including quercetin, myricitrin, and ellagic acid, which exhibit antioxidant and anti-inflammatory properties, were identified in the C. turczaninowii extract through ultra-performance liquid chromatography-quadrupole-time of flight (UPLC-Q-TOF) mass spectrometry. In conclusion, C. turczaninowii may alleviate high glucose-induced inflammation and arterial damage in hASMCs, and may have potential in the treatment of hyperglycemia-induced atherosclerosis.