Korea Research Institute of Bioscience and Biotechnology
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Phloretin inhibits the human prostate cancer cells through the generation of reactive oxygen species
No full textPhloretin is a flavonoid with known anticancer activities. However, we do not fully understand how phloretin mitigates prostate cancer on the molecular level. In the present study, we examined changes in proliferation, colony formation, and migration after phloretin treatment in human prostate cancer cells PC3 and DU145. We measured reactive oxygen species (ROS) and gene expression. Phloretin increased ROS and suppressed cell proliferation, migration, and colony formation in both cell lines. Additionally, phloretin treatment increased oxidative stress, as demonstrated through lower antioxidant enzymes (catalase, SOD2, Gpx1, Gpx3). In addition, their regulator CISD2 decreased in expression. We also found that increased ROS significantly downregulated multiple components of the Wnt/β-catenin signaling pathway (β-catenin, TCF4, FoxA2, c-Myc) and Twist1. Thus, anticancer activity of phloretin against human prostate cancer cells occurs through generating ROS to influence Wnt/β-catenin signaling. The results of this study suggest that phloretin has a therapeutic effect on prostate cancer in vitro, inhibiting the proliferation and migration of cancer cell lines PC3 and DU145. The mechanism of phloretin appears to be increasing ROS production. We thus recommend phloretin as a promising anticancer therapeutic agent.
패턴인식 수용체와 상호작용을 통한 인플루엔자 바이러스 신규 병원성 기전 규명
No full text패턴인식 수용체와 상호작용을 통한 인플루엔자 바이러스 신규 병원성 기전 규명PRM096201
Study on the improvement mechanism of energy consumption based on post-translational modification (PTM) analysis of WAT browning
No full text갈색지방화 조절단백질의 PTM분석 기반 생체 에너지 소비 향상 기전연구OGM453191
Mass production of Pinellia ternata multiple egg-shaped micro-tubers (MESMT) through optimized growth conditions for use in ethnomedicine
No full textThe root tuber of Pinellia ternata (Thunb.) Briet has been used over the years in traditional medicine to treat myriad of diseases. In this study, a standard in vitro mass production of P. ternata multiple egg-shaped micro-tubers (MESMT) protocol was developed to meet the increasing demand for P. ternata tubers. Ten different types of media, as well as different sucrose and plant growth regulators (PGRs) concentrations were evaluated for their suitability to enhance optimum P. ternata MESMT production. At 6 weeks of culture, LS medium supplemented with 6% sucrose, 1.0 mg/L BA cytokinin and 0.5 mg/L IAA auxin was the most suitable condition for the mass production of P. ternata MESMT. Liquid chromatography-mass spectrometry and Fourier transform infrared spectroscopy analyses of the P. ternata MESMT harvested after 25 weeks of growth in soil showed a close similarity and drug equivalence to the commercialised P. ternata sample. Although these results provide a basis for future mass production of P. ternata MESMT, further testing should be conducted to validate this patented P. ternata MESMT (No. 10-1955009) for use in ethnomedicine. This is the first study to report on the optimal conditions for P. ternata MESMT increased mass production for traditional medicine purpose.
Prunus serrulata var. spontanea inhibits mast cell activation and mast cell-mediated anaphylaxis
No full textETHNOPHARMACOLOGICAL RELEVANCE: A promising approach to treat a variety of diseases are considered as complementary and alternative herbal medicines. Prunus serrulata var. spontanea L. (Rosaceae) is used as herbal medicine to treat allergic diseases according to the Donguibogam, a tradition medical book of the Joseon Dynasty in Korea.
AIM OF THE STUDY: We prepared the aqueous extract of the bark of P. serrulata (AEBPS) and aimed to investigate the effects in mouse anaphylaxis models and various types of mast cells, including RBL-2H3, primary cultured peritoneal and bone marrow-derived mast cells.
MATERIALS AND METHODS: We used ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) and immunoglobulin (Ig) E-mediated passive cutaneous anaphylaxis (PCA) models, in vivo. The control drug dexamethasone (10 mg/kg) was used to compare the effectiveness of AEBPS (1-100 mg/kg). In vitro, IgE-stimulated mast cells were used to confirm the role of AEBPS (1-100 μg/mL). For statistical analyses, p values less than 0.05 were considered to be significant.
RESULTS: In ASA model, oral administration of AEBPS suppressed the hypothermia and increased level of serum histamine in a dose-dependent manner. AEBPS attenuated the serum IgE, OVA-specific IgE, and interleukin (IL)-4. Oral administration of AEBPS also blocked mast cell-dependent PCA. AEBPS suppressed degranulation of mast cells by reducing intracellular calcium level in mast cells. AEBPS inhibited tumor necrosis factor-α and IL-4 expression and secretion in a concentration-dependent manner through the reduction of nuclear factor-κB.
CONCLUSIONS: On the basis of these findings, AEBPS could serve as a potential therapeutic target for the management of mast cell-mediated allergic inflammation and as a regulator of mast cell activation.
Scrophularia buergeriana attenuates allergic inflammation by reducing NF-κB activation
No full textBACKGROUND: Scrophularia buergeriana Miq. (Scrophulariaceae) (SB) has been used as an oriental medicine for the treatment of inflammatory diseases, such as neuritis and pharyngolaryngitis.
PURPOSE: We explored the therapeutic effects of S. buergeriana ethanol extract (SBE) on airway inflammation in ovalbumin (OVA)-induced asthmatic mice and lipopolysaccharide (LPS)-stimulated RAW264.7 cells.
METHODS: Mice were intraperitoneally injected with OVA on days 0 and 14 to elevate the immune response. On days 21 to 23, the mice were challenged with OVA solution and SBE (20 and 40 mg/kg) was administered daily by oral gavage from days 18 to 23. RAW264.7 cells were pretreated with SBE 1 h before LPS stimulation.
RESULTS: SBE administration effectively suppressed inflammatory cell infiltration, the expression of interleukin (IL)-5, IL-13, and IL-17, immunoglobulin E, and airway hyperresponsiveness in an OVA-induced allergic asthma model. A reduction in histological alterations, including airway inflammation and mucus hypersecretion, was observed. These effects of SBE were accompanied by a decrease in matrix metalloproteinase-9 (MMP-9) expression and nuclear factor kappa B (NF-κB) phosphorylation. These responses were observed in LPS-stimulated RAW264.7 cells. SBE treatment reduced the mRNA expression of tumor necrosis factor (TNF)-α, IL-6, and MMP-9, and NF-κB phosphorylation, in LPS-stimulated RAW264.7 cells.
CONCLUSION: Our results indicated that SBE effectively attenuated airway inflammation in an OVA-induced allergic asthma model. These properties of SBE were thought to be involved in the suppression of NF-κB phosphorylation, suggesting that the material has the potential to regulate the development of allergic asthma.
PIN-mediated polar auxin transport facilitates root obstacle avoidance
No full textPlants sense mechanical stimuli to recognise nearby obstacles and change their growth patterns to adapt to the surrounding environment. When roots encounter an obstacle, they rapidly bend away from the impenetrable surface and find the edge of the barrier. However, the molecular mechanisms underlying root-obstacle avoidance are largely unknown. Here, we demonstrate that PIN-FORMED (PIN)-mediated polar auxin transport facilitates root bending during obstacle avoidance. We analysed two types of bending after roots touched barriers. In auxin receptor mutants, the rate of root movement during first bending was largely delayed. Gravity-oriented second bending was also disturbed in these mutants. The reporter assays showed that asymmetrical auxin responses occurred in the roots during obstacle avoidance. Pharmacological analysis suggested that polar auxin transport mediates local auxin accumulation. We found that PINs are required for auxin-assisted root bending during obstacle avoidance. We propose that rapid root movement during obstacle avoidance is not just a passive but an active bending completed through polar auxin transport. Our findings suggest that auxin plays a role in thigmotropism during plant-obstacle interactions.
Phenolic-enriched blueberry-leaf extract attenuates glucose homeostasis, pancreatic β-cell function, and insulin sensitivity in high-fat diet-induced diabetic mice
No full textBlueberry fruit exhibits strong antioxidant activity owing to the presence of anthocyanin. As blueberry-leaf extract (BLE) contains chlorogenic acid and flavonol glycosides, we hypothesized that phenolic-enriched BLE would improve glucose homeostasis and insulin sensitivity. In this study, we examined whether BLE administration decreases the glucose levels and enhances the pancreatic function in mice with high-fat diet (HFD)-induced obesity and diabetes. C57BL/6J mice were divided into the following four groups: control diet (CD), HFD (60 kcal% fat diet), BLE (HFD with 1% BLE wt/wt diet), and yerba mate extract (YME; HFD with 0.5% YME wt/wt diet). Dietary BLE and YME reduced glucose tolerance, body weight, and plasma glucose, glycated hemoglobin, insulin, homeostasis model assessment of insulin resistance, triglyceride (TG), and non-esterified fatty acid levels. Compared with those of the HFD group, BLE was found to significantly reduce the pancreatic islet size and insulin content. Moreover, it increased the mRNA levels of pancreatic β-cell proliferation-related genes, Ngn3, MafA, Pax4, Ins1, and Ins2, and pancreatic insulin signaling-related genes, IRS-1, IRS-2, PIK3ca, PDK1, PKCε, and GLUT-2, and decreased the transcriptional expression of the β-cell apoptosis-related gene, FoxO1. Both BLE and YME improved insulin sensitivity by inhibiting TG synthesis and enhancing lipid utilization in the liver and white adipose tissue (WAT). In pancreatic MIN6 β-cells, BLE and its main component (chlorogenic acid) increased β-cell proliferation and promoted insulin signaling. Overall, BLE enriched with phenolic compounds has the capacity to prevent HFD-induced glucose tolerance and hyperglycemia by improving the pancreatic β-cell function.
β-glucooligosaccharides derived from barley β-glucan promote growth of lactic acid bacteria and enhance nisin Z secretion by Lactococcus lactis
No full textThe present study assessed the effects of β-glucooligosaccharides (β-GOS) derived from barley β-glucan on the proliferation and antimicrobial activity of probiotics. All cocci examined in this study and several species of Lactobacilli and bifidobacteria were able to utilize β-GOS as a sole carbon source. In addition, the absence of significant growth of certain pathogens on β-GOS compared to prebiotics fructo-oligosaccharide (FOS) and inulin substrates demonstrates the probiotic specificity of β-GOS metabolism. Increased anti-microbial activities were observed in Lactococcus lactis subsp. lactis, Lactobacillus reuteri, and Pediococcus acidilactici grown in media with β-GOS as the sole carbon source over glucose. β-GOS enabled sustained L. lactis subsp. lactis growth in the exponential phase, resulting in an approximately 25% increase in nisin Z production compared with glucose. These results suggest that β-GOS can selectively modulate probiotic growth in particular cocci, and antimicrobial activity, with important implications for future research in nutrition as well as industrial applications.
Antiangiogenic potentials of ahpatinins obtained from a Streptomyces species
No full textWhile exploring new angiogenesis inhibitors from microbial metabolites, we recently isolated ahpatinins C, E, and G from a soil？derived Streptomyces sp. 15JA150. Ahpatinins C, E and G are known to have pepsin and renin inhibitory activities; however, their antiangiogenic activities and underlying molecular mechanisms have not been fully elucidated. In the present study, the antiangiogenic properties of ahpatinins C, E and G were investigated. The results revealed that the natural compounds significantly inhibited the vascular endothelial growth factor (VEGF)？induced proliferation, invasion, adhesion, and tube formation of human umbilical vein endothelial cells (HUVECs) without exhibiting any cytotoxicity. It was also revealed that ahpatinin E effectively suppressed the neovascularization of the chorioallantoic membranes in growing chick embryos. Notably, ahpatinins C, E, and G led to the downregulation of VEGF？induced activation of VEGF receptor 2 (VEGFR2) and its downstream signaling mediators, including AKT, ERK1/2, JNK, p38, and NF？κB, in HUVECs. Moreover, they reduced the expression of matrix metalloproteinase (MMP)？2 and MMP？9 in the HUVECs following stimulation with VEGF. Furthermore, ahpatinins C, E, and G reduced the tumor cell？induced invasion and tube forming abilities of HUVECs, as well as the expression of VEGF, by suppressing hypoxia？inducible factor？1α (HIF？1α) activity in U87MG glioblastoma cells. Collectively, the present findings indicated that ahpatinins C, E, and G may be used in anticancer therapy by targeting tumor angiogenesis through the inhibition of both VEGFR2 and HIF？1α pathways.