• Journal of Life Science
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• v.29 no.1
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• pp.129-134
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• 2019

In a previous study, we isolated 11 different kinds of compounds from ethyl acetate fractions of lees (jubak) which is a by-product of Korean traditional wine production. These compounds were identified as caffeic acid, coumaric acid, D-mannitol, ferulic acid, hesperetin, hesperidin, naringenin, naringin, sinapic acid, syringic acid, and vanilic acid. To evaluate their anti-inflammatory activities in an in vitro model, nitric oxide (NO) production was measured in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells after the treatment of these cells with each compound. Among the various chemicals, hesperetin and naringenin showed the highest inhibition of NO production in the LPS-activated RAW 264.7 cells. Hesperetin was chosen for further study because of its strong anti-inflammatory activity and because the mechanisms underlying its anti-inflammatory properties still remain unclear. Our results showed that hesperetin dramatically inhibited NO production in a dose-dependent manner as compared with in an LPS-only treated group, without affecting cell viability. In addition, hesperetin reduced the protein expression of the pro-inflammatory gene inducible nitric oxide synthase (iNOS) in a dose-dependent manner, whereas it did not affect cyclooxygenase-2 (COX-2) expression. Furthermore, hesperetin inhibited phosphorylation of p38 mitogen- activated protein kinase (MAPK) and extracellular signal regulated kinase (ERK) 1/2, whereas it did not affect phosphorylation of c-jun N- terminal kinase (JNK). The results indicated that hesperetin regulated the LPS-induced inflammatory response by suppressing p38 MAPK and ERK1/2 signaling. Overall, our results may help to understand the mechanisms underlying the anti-inflammatory activity mediated by hesperetin.

• Journal of Ecology and Environment
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• v.45 no.3
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• pp.143-151
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• 2021

Background: Plants are able to optimize defense responses induced by various herbivores, which have different feeding strategies. Local and systemic responses within a plant after herbivory are essential to modulate herbivore-specific plant responses. For instance, leaf-chewing herbivores elicit jasmonic acid signaling, which result in the inductions of toxic chemicals in the attacked leaf (tissue-specific responses) and also in the other unattacked parts of the plant (systemic responses). Root herbivory induces toxic metabolites in the attacked root and alters the levels of transcripts and metabolites in the unattacked shoot. However, we have little knowledge of the local and systemic responses against stem-boring herbivores. In this study, we examined the systemic changes in metabolites in the wild tobacco Nicotiana attenuata, when the stem-boring herbivore Trichobaris mucorea attacks. Results: To investigate the systemic responses of T. mucorea attacks, we measured the levels of jasmonic acid (JA), JA-dependent secondary metabolites, soluble sugars, and free amino acids in 7 distinct tissues of N. attenuata: leaf lamina with epidermis (LLE), leaf midrib (LM), stem epidermis (SE), stem pith (SP), stem vascular bundle (SV), root cortex with epidermis (RCE), and root vascular bundle (RV). The levels of JA were increased in all root tissues and in LM by T. mucorea attacks. The levels of chlorogenic acids (CGAs) and nicotine were increased in all stem tissues by T. mucorea. However, CGA was systematically induced in LM, and nicotine was systematically induced in LM and RCE. We further tested the resource allocation by measuring soluble sugars and free amino acids in plant tissues. T. mucorea attacks increased the level of free amino acids in all tissues except in LLE. The levels of soluble sugars were significantly decreased in SE and SP, but increased in RV. Conclusions: The results reveal that plants have local- and systemic-specific responses in response to attack from a stem-boring herbivore. Interestingly, the level of induced secondary metabolites was not consistent with the systemic inductions of JA. Spatiotemporal resolution of plant defense responses against stem herbivory will be required to understand how a plant copes with attack from herbivores from different feeding guilds.

• Journal of Ginseng Research
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• v.45 no.3
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• pp.401-407
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• 2021

Background: Gintonin is an exogenous ginseng-derived G-protein-coupled lysophosphatidic acid (LPA) receptor ligand. LPA induces in vitro morphological changes and migration through neuronal LPA1 receptor. Recently, we reported that systemic administration of gintonin increases blood-brain barrier (BBB) permeability via the paracellular pathway and its binding to brain neurons. However, little is known about the influences of gintonin on in vivo neuron morphology and migration in the brain. Materials and methods: We examined the effects of gintonin on in vitro migration and morphology using primary hippocampal neural precursor cells (hNPC) and in vivo effects of gintonin on adult brain neurons using real time microscopic analysis and immunohistochemical analysis to observe the morphological and locational changes induced by gintonin treatment. Results: We found that treating hNPCs with gintonin induced morphological changes with a cell rounding following cell aggregation and return to individual neurons with time relapses. However, the in vitro effects of gintonin on hNPCs were blocked by the LPA1/3 receptor antagonist, Ki16425, and Rho kinase inhibitor, Y27632. We also examined the in vivo effects of gintonin on the morphological changes and migration of neurons in adult mouse brains using anti-NeuN and -neurofilament H antibodies. We found that acute intravenous administration of gintonin induced morphological and migrational changes in brain neurons. Gintonin induced some migrations of neurons with shortened neurofilament H in the cortex. The in vivo effects of gintonin were also blocked by Ki16425. Conclusion: The present report raises the possibility that gintonin could enter the brain and exert its influences on the migration and morphology of adult mouse brain neurons and possibly explains the therapeutic effects of neurological diseases behind the gintonin administration.

• The Korea Journal of Herbology
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• v.32 no.2
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• pp.77-85
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• 2017

Objectives : This study aimed to investigate the unknown mechanisms behind the anti- inflammatory activity of Hyeonto-dan(HT) 70% ethanol extract on LPS-stimulated RAW 264.7 cells. Methods : Cells were treated with Hyeonto-dan 1 h prior to addition of 200 ng/mL of LPS. Cell viability was measured by the MTS assay. Nitric oxide levels were determined by the Griess assay. $PGE_2$ were measured using EIA kit. Pro-inflammatory cytokine production was measured by the enzyme-linked immunosorbent assay (ELISA). The expression of COX-2, iNOS, and MAPKs was investigated by Western blot, qRT-PCR. $NF-{\kappa}B$/p65 localization and interaction of the TLR-4 receptor with LPS was examined by immunofluorescence assays. Results : Hyeonto-dan had no cytotoxicity at the measured concentration. Hyeonto-dan inhibited NO production and pro-inflammatory cytokines such as IL-6, $TNF-{\alpha}$, and PGE2 as well as the protein and mRNA expression of iNOS and COX-2. Moreover, Hyeonto-dan inhibited the interaction between LPS and TLR-4 in murine macrophages. It suppressed phosphorylation of extracellular signal-regulated kinase (ERK 1/2), c-jun N-terminal kinase (JNK 1/2) and p38. Finally, it inhibited translocation of $NF-{\kappa}B$ in response to competitive LPS. Conclusions : Based on the results of this study, Hyeonto-dan inhibited the binding of TLR-4 receptor to LPS and inhibited the phosphorylation of extracellular signaling pathway MAPKs. These inhibitory effects are thought that the amount of $NF-{\kappa}B$ delivered to the nucleus was decreased and the inflammatory reaction was prevented by decreasing the production of LPS-induced $PGE_2$, NO, IL-6 and $TNF-{\alpha}$.

• Journal of Life Science
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• v.33 no.1
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• pp.73-81
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• 2023

In the present study, we prepared hot water extracts and the subsequent organic solvent fractions of methanol extracts of Houttuynia cordata (HC) and Lespedeza cuneata (LC), and investigated their anti-inflammatory effects on lipopolysaccharide-stimulated RAW264.7 cells. Among the treated samples, hexane, chloroform, and ethyl-acetate fractions of HC and LC inhibited nitric oxide (NO) production in a dose-dependent manner, and decreased inducible nitric oxide synthase (iNOS) protein expression. And, we analyzed the flavonoid contents of the ethyl-acetate fraction of HC and LC, and chose apigenin for the further experiments because apigenin was one of flavonoids commonly found in HC and LC. Apigenin dramatically inhibited NO production in a dose-dependent manner without affecting cell viability and decreased iNOS and cyclooxygenase-2 (COX-2) expression. In addition, apigenin suppressed the phosphorylation of p38 and Jun N-terminal kinase (JNK) indicating that apigenin exerts anti-inflammatory activity via the mitogen-activated protein kinase (MAPK) signaling pathway. Subsequently, we conducted RNA-sequencing analysis to detect differentially expressed genes upon apigenin treatment. Among the down-regulated genes, four cytokine genes (interleukin (IL)-1α, IL-1β, IL-6, and colony stimulating factor 2 (CSF2)) were selected for the further analysis, and the reduction of their expression by apigenin was confirmed with quantitative real-time polymerase chain reaction. Overall, our results suggest that Houttuynia cordata and Lespedeza cuneata have the anti-inflammatory effects and apigenin can be the one of key molecules responsible for their anti-inflammatory activities.

• IMMUNE NETWORK
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• v.20 no.4
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• pp.32.1-32.15
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• 2020

Influenza virus is the major cause of seasonal and pandemic flu. Currently, oseltamivir, a potent and selective inhibitor of neuraminidase of influenza A and B viruses, is the drug of choice for treating patients with influenza virus infection. However, recent emergence of oseltamivir-resistant influenza viruses has limited its efficacy. Morin hydrate (3,5,7,2',4'-pentahydroxyflavone) is a flavonoid isolated from Morus alba L. It has antioxidant, anti-inflammatory, neuroprotective, and anticancer effects partly by the inhibition of the NF-κB signaling pathway. However, its effects on influenza virus have not been studied. We evaluated the antiviral activity of morin hydrate against influenza A/Puerto Rico/8/1934 (A/PR/8; H1N1) and oseltamivir-resistant A/PR/8 influenza viruses in vitro. To determine its mode of action, we carried out time course experiments, and time of addition, hemolysis inhibition, and hemagglutination assays. The effects of the co-administration of morin hydrate and oseltamivir were assessed using the murine model of A/PR/8 infection. We found that morin hydrate reduced hemagglutination by A/PR/8 in vitro. It alleviated the symptoms of A/PR/8-infection, and reduced the levels of pro-inflammatory cytokines and chemokines, such as TNF-α and CCL2, in infected mice. Co-administration of morin hydrate and oseltamivir phosphate reduced the virus titers and attenuated pulmonary inflammation. Our results suggest that morin hydrate exhibits antiviral activity by inhibiting the entry of the virus.

• Korean Journal of Pharmacognosy
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• v.40 no.3
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• pp.196-204
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• 2009

This study was carried out to investigate the in vivo and in vitro inhibitory effect of a traditional herbal complex (HC) extract prepared from a mixture of four oriental herbs (Dioscorea Rhizoma, Glycine soja Sieb. et Zucc, Bombycis corpus, Fermented Glycine soja) that have been widely used for the treatment and prevention of diabetes mellitus on hyperglycemia. The water extract of HC showed potent inhibitory effect on $\alpha$-glucosidase with $IC_{50}$ value of 1.24 mg/mL. Additionally, the ethanol extract of HC was also found to exhibit significant inhibitory effect against protein tyrosine phosphatase $1{\beta}$ ($PTP1{\beta}$), which is known as a major regulator of both insulin and leptin signaling. In the $PTP1{\beta}$ inhibitory assay, the most active n-hexane fraction obtained from the ethanol extract of HC, was identified as a mixture of fatty acid derivatives by gas chromatography-mass spectrometry (GC-MS). In high-fat diet-low dose streptozotocin (STZ)-induced diabetic rat, the water extract of HC improved the oral glucose intolerance as compared with rosiglitazone. HC also caused a marked decrease of body weight and fasting blood glucose and a significant improvement on glucose tolerance in metabolic syndrome mice model. These findings support that this traditional HC may be useful in the control of blood glucose in diabetes mellitus and metabolic syndrome.

• Journal of Life Science
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• v.13 no.5
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• pp.596-603
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• 2003

Cells respond to an accumulation of unfolded proteins in the endoplasmic reticulum (ER) by increasing transcription of genes encoding molecular chaperones and folding enzymes. The information is transmitted from the ER lumen to the nucleus by intracellular signaling pathway, called the unfolded protein response (UPR). To obtain genes related to UPR from B. mori, the cDNA library was constructed with mRNA isolated from Bm5 cell lines in which N-glycosylation was inhibited by tunicamycin treatment. From the cDNA library, we selected 40 clones that differentially expressed when cells were treated with tunicamycin. Among these clones, we have isolated ATFC gene showing similarity with Hac1p, encoding a bZIP transcription factor of 5. cerevisiae. Basic-leucine zipper (bZIP) domain in amino acid sequences of ATFC shared homology with yeast Hac1p. Also, ATFC is up-regulated by accumulation of unfolded proteins in the ER through the treatment of ER stress drugs. Therefore we suggest that ATFC represents a major component of the putative transcription factor responsible for the UPR leading to the induction of ER-localized stress proteins.

• Journal of Plant Biotechnology
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• v.41 no.4
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• pp.180-193
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• 2014

In plants, a shoot apex has a small region known as the shoot apical meristem (SAM) having a group of dividing (initiating) cells. The SAM gives rise to all the groundabove structures of plants throughout their lifetime, and thus it plays important role in growth and development of plants. This review describes theories to explain the SAM organization and function developed over the last 250 years. Since in 1759 German botanist C. F. Wolff has described firstly the SAM, in 1858 Swiss botanist C. N${\ddot{a}}$geli proposed the apical cell theory from the observation of a large single apical cell in the SAM of seedless vascular plants: however, this view was recognized to be unsuitable to seed plants. In 1868, German botanist J. Hanstein suggested the histogen theory: this concept subdividing the SAM into dermatogen, periblem, and plerome was unable to generally apply to seed plants. In 1924, German botanist A. Schmidt proposed the tunica-corpus theory from the examination of angiosperm SAM in which two parts show different planes of cell division: this theory was proved to be not suitable to gymnosperm SAM, not have stable surface tunica layer. In 1938, American botanist A. Foster described zones in gymnosperm SAM based on the cytohistologic differentiation and thus called it a cytohistological zonation theory. With works by E. Gifford, in 1954, this zonation pattern was demonstrated to be also applicable to angiosperm SAM. As another theory, in 1952 French botanist R. Buvat proposed the m${\acute{e}}$rist${\grave{e}}$me d'attente (waiting meristem) theory: however, this concept was confuted because of its negation of function during vegetative growth phase to central initial cells. Rescent studies with Arabidopsis thaliana have found that formation and maintenance of the SAM are under the control of selected genes: SHOOTMERISTEMLESS (STM) gene forms the SAM, and WUSCHEL (WUS) and CLAVATA (CLV) genes function in maintaining the SAM; signaling between WUS and CLV genes act through a negative feedback loop.

• Journal of Life Science
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• v.31 no.8
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• pp.699-709
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• 2021

Muscle mass improvement through lifestyle modification has been shown to reduce the risk of metabolic syndrome. This study examined the capacity of ethanol extracts of Scytosiphon lomentaria (SLE) to suppress the bioactivity of myostatin, a potent negative regulator of skeletal muscle mass, as well as the effect of SLE treatment on metabolic homeostasis in obese zebrafish induced by high feeding. A total of 10 ㎍/ml SLE completely blocked myostatin (1 nM/ml) signaling in the pGL3-(CAGA)₁₂ luciferase assay and suppressed myostatin-induced Smad2 phosphorylation in the Western blot analysis. In the zebrafish larvae analysis, the whole body glucose concentration of the high feeding control (HFC) group was significantly higher than that of the normal feeding control (NFC) group. However, the glucose levels of the high feeding group treated with 12.5 ug SLE and of the high feeding group treated with 18.75 ug SLE were similar to those of the NFC group. The mRNA expression level of the GLUT2 gene of the HFC group was significantly lower than that of the NFC group. SLE treatment restored the expression of the GLUT2 gene to a level that was close to that of the NFC group, indicating that SLE is capable of regulating glucose levels in zebrafish larvae. The current results highlight the potential of SLE as a natural MSTN inhibitor and supplement that can be used to facilitate the treatment of metabolic syndrome.