• Journal of Life Science
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• v.28 no.11
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• pp.1332-1338
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• 2018

Activated microglia, induced by various pathogens, protect neurons and maintain homeostasis of the central nervous system (CNS). However, severe activation causes neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease because of the secretion of various neurotoxic molecules, such as nitric oxide (NO), prostaglandin (PG), and pro-inflammatory cytokines. Because chronic microglial activation endangers neuronal survival, negative regulators of microglial activation have been identified as potential therapeutic candidates for treatment of many neurological diseases. One potential source of these regulators is Locusta migratoria, a grasshopper of the Acrididae, usually 4-6 cm in size, belonging to the family of large insects in Acrididae. This grasshopper is an edible insect resource that can be consumed by humans as protein source or used for animal feed. The aim of the present study was to examine the inhibitory effects of a L. migratoria ethanol extract (LME) on the production of inflammatory mediators in LPS-stimulated BV-2 microglia cells. The extract significantly inhibited the NO, iNOS, COX-2, and pro-inflammatory cytokine ($TNF-{\alpha}$, IL-6 and $IL-1{\beta}$) levels in BV-2 microglia cell. Because the inhibition of microglial activation may be an effective solution for treating brain disorders like Alzheimer's and Parkinson's diseases, these results suggest that LME may be a potential therapeutic agent for the treatment of brain disorders induced by neuroinflammation.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.2
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• pp.151-159
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• 2019

Pruritus (itching) is classically defined as an unpleasant cutaneous sensation that leads to scratching behavior. Although the scientific criteria of classification for pruritic diseases are not clear, it can be divided as acute or chronic by duration of symptoms. In this study, we investigated whether skin injury caused by chemical (contact hypersensitivity, CHS) or physical (skin-scratching stimulation, SSS) stimuli causes initial pruritus and analyzed gene expression profiles systemically to determine how changes in skin gene expression in the affected area are related to itching. In both CHS and SSS, we ranked the Gene Ontology Biological Process terms that are generally associated with changes. The factors associated with upregulation were keratinization, inflammatory response and neutrophil chemotaxis. The Kyoto Encyclopedia of Genes and Genomes pathway shows the difference of immune system, cell growth and death, signaling molecules and interactions, and signal transduction pathways. Il1a, Il1b and Il22 were upregulated in the CHS, and Tnf, Tnfrsf1b, Il1b, Il1r1 and Il6 were upregulated in the SSS. Trpc1 channel genes were observed in representative itching-related candidate genes. By comparing and analyzing RNA-sequencing data obtained from the skin tissue of each animal model in these characteristic stages, it is possible to find useful diagnostic markers for the treatment of itching, to diagnose itching causes and to apply customized treatment.

• Korean Journal of Food Science and Technology
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• v.51 no.1
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• pp.70-80
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• 2019

The aim of this study was to investigate the effects of red ginseng-derived non-saponin fraction (NSF) on inflammatory responses and monocyte-to-macrophage differentiation in RAW264.7 and THP-1. NSF effectively inhibited inflammatory responses by downregulating nitric oxide (NO) production and protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). NSF ($2000{\mu}g/mL$) decreased the levels of NO, iNOS, and COX-2 by 33, 83, and 64%, respectively. NSF inhibited the differentiation of monocyte-to-macrophage by decreasing cell adherence along with downregulation of the cluster of differentiation molecule $11{\beta}$ ($CD11{\beta}$) and CD36. In addition, pro-inflammatory cytokines, such as tumor necrosis factor-alpha, interleukin 6, and monocyte chemoattractant protein 1 (MCP-1), were significantly reduced with NSF treatment. The NSF-mediated inhibition of inflammatory responses was due to the regulation of nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). NSF effectively suppressed the translocation of $NF-{\kappa}B$ into the nucleus, while nuclear Nrf2 and its target protein, heme oxygenase-1, levels were significantly increased.

• Pediatric Infection and Vaccine
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• v.26 no.1
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• pp.51-59
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• 2019

Purpose: The aim of this study was to evaluate the relationships between cytokine and chemokine levels and the clinical severity of Mycoplasma pneumoniae pneumonia. Methods: A retrospective analysis of clinical and laboratory parameters were performed. Serum levels of interleukin (IL)-6, IL-8, IL-10, IL-18, interferon-${\gamma}$-inducible protein-10 (IP-10), macrophage inflammatory $protein-1{\beta}$, and tumor necrosis $factor-{\alpha}$ were measured. The severity of patients' clinical course and radiologic findings were also assessed. Results: Seventy-two patients (35 males and 37 females) with a median age of 3.9 years (range, 1-16 years) were enrolled. Patients with lobar pneumonia (n=29) had significantly higher C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and IL-18 values than those with broncho-interstitial pneumonia (n=43). However, the cytokine and chemokine values did not differ between the group that was treated with corticosteroids (n=31) and the one that was not (n=41). The CRP, ESR, lactate dehydrogenase (LDH), IL-18, and IP-10 values showed positive correlations with fever duration prior to admission. The CRP and ESR values were positively correlated with IL-18, and LDH, with IP-10 levels. Conclusions: CRP, ESR, LDH, IL-18, and IP-10 values were associated with the severity of the disease, manifesting lobar pneumonia or prolonged fever duration prior to admission.

• Korean Journal of Pharmacognosy
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• v.50 no.3
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• pp.219-225
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• 2019

This study was done to examine immunomodulative effects of aged doraji (AD) in the immune-suppressed mice induced by cyclophosphamide. The immune-stimulating effects of ethanol AD extract in in vivo at 75 and 150 mg/kg body weight (BW) for AD and 2AD groups were evaluated and compared to the normal doraji group (2ND, 150 mg/kg BW) treated with a doraji without aging process. After the 10 days of oral supplement, body and immune related organ weights, serum immunoglobulin G (IgG) and cytokines levels, splenocytes proliferation rate, and splenic NK cell activity were measured as immune-related biomarkers. Body weight and serum IgG level increased in the 2AD group. But, the serum Th2 cytokine (IL-6, $TNF-{\alpha}$) levels were lower in the AD and 2AD groups, respectively. Splenic T cell and B cell proliferation and NK cell activity increased in the doraji groups and the significant increases were found only in the 2AD group. Thus, the aged doraji extract may affect body weight, serum IgG level, splenocytes proliferation, and splenic NK cell activity, and normalize the Th2 cytokine levels in the immune-suppressed mice. The results suggest that the aged doraji improves effectively immune system rather than the normal one.

• Korean Journal of Pharmacognosy
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• v.50 no.1
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• pp.37-45
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• 2019

Portulaca oleracea L. (PL) has been used in traditional medicine herb for treatment of various diseases, such as diarrhea, dysentery, and skin inflammation. Previous studies have shown that the PL regulates the inflammation by inhibition of pro-inflammatory cytokines. Although PL might have improvement effects of intestinal function and bioactive effects, there are not enough studies to demonstrate. This study investigated the effects of KDC16-2 on the improvement of intestinal function and anti-inflammatory effects in vivo and in vitro. The improvement effect of intestinal function was measured fecal amount, water content and intestinal transit rate in KDC16-2 treated ICR mice. As results, compared with the control group, the KDC16-2 group showed a significant increase in wet fecal weight, dry fecal weight and fecal water content. The intestinal transit rate of KDC16-2 group was significantly increased. Based on the results, KDC16-2 is considered to have effects on improving intestinal function. The effect of anti-inflammatory demonstrated by using dextran sulfate sodium (DSS)-induced colitis mice. The mice were administered 3% DSS along with KDC16-2 (100, 300 mg/kg) for 14 days. DSS-induced colitis mice were significantly ameliorated in KDC16-2 treated group, including body weight loss, colon length shortening, tight junction protein of colon and histological colon injury. The levels of inflammatory mediators (IgG2a, IgA, C-reactive protein and Myeloperoxidase) and pro-inflammatory cytokines (tumor necrosis factor (TNF)-${\alpha}$, Interleukin (IL)-6) which are involved in inflammatory responses were increased in the DSS-treated group as compared to those in the control group, and the levels were significantly decreased in the KDC16-2 groups. In addition, we investigated the impact of KDC16-2 on lipopolysaccharide (LPS)-induced inflammatory responses in J774A.1 cells. KDC16-2 inhibited production of prostaglandin E2 (PGE2) and reactive oxygen species (ROS). These results suggested that the KDC16-2 could effectively alleviate the dysfunction of intestinal and inflammatory mediators. Thus, these KDC16-2 can be potentially used as health functional food of intestinal.

• The Journal of Internal Korean Medicine
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• v.40 no.1
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• pp.13-37
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• 2019

Objectives: The purpose of this study was to assess the effects of Korean medicine for non-alcoholic fatty liver disease (NAFLD). We analyzed the result of randomized controlled trials (RCTs) that applied Korean medicine to NAFLD patients through meta analysis and systematic review. Methods: The key question was to the effects of Korean medicine for NAFLD patients according to the PICO-SD (participants, intervention, comparison, outcome, study design) and we included only RCTs. We searched 10 databases including NDSL, KMBASE, KISS, KISTI, KoreaMed, Koreantk, OASIS, Cochrane, Pubmed, EMBASE without a language restriction. We assessed risk of bias by Cochrane group's Risk of Bias tool. Results: The finally selected 12 RCTs were analyzed. Total number of participants was 1189 (male 719, female 470) as 684 and 505 in the oriental medicine group (i.e. herbal drugs, acupuncture, acupoint embedding therapy) and control group (conventional drugs, placebo), respectively. The meta analysis results of examining 7 RCTs comparing the therapeutic efficacy of herbal medicine with that of Western medicine showed statistically significant (p<0.05) differences in the efficacy evaluation, liver function test results, blood lipids, and TNF-${\alpha}$. Furthermore, the meta analysis results of investigating 3 RCTs comparing the therapeutic efficacy of herbal medicine with that of a placebo showed statistically significant (p<0.05) differences in the liver function test results, blood lipids, and waist circumference. Conclusions: The research showed that Korean medicine for NAFLD can be effective treatment. But more studies are required to enhance the level of evidence and we should report on safety.

• Journal of Life Science
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• v.29 no.2
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• pp.256-264
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• 2019

Lymphotoxin ${\beta}$ receptor ($LT{\beta}R$), a member of the tumor necrosis factor receptor family, plays an important role in lymphoid tissue's architecture and organogenesis. In contrast, MLCK and ROCK play critical roles in the regulation of stress fiber (SF) formation in cells. To determine whether $LT{\beta}R$ stimulation in fibroblastic reticular cells (FRCs) is involved in these signaling pathways, myosin light chain kinase inhibitor-7 (ML-7) was used to inhibit them. ML7-treated FRCs completely blocked SFs and showed retraction and shrinkage processes comparable to those observed in agonistic anti-$LT{\beta}R$ antibody-treated cells. The inhibition of ROCK activity with Y27632-induced changes in actin cytoskeleton organization and cell morphology in FRCs. Actin bundles rearranged into SFs, and phospho-myosin light chain (p-MLC) co-localized in FRCs. We checked the level of Rho-guanosine diphosphate (RhoGDP)/guanosine triphosphate (GTP) exchange activity using FRC lysate. When $LT{\beta}R$ was stimulated with agonistic anti-$LT{\beta}R$ antibodies, Rho-GDP/GTP exchange activity was markedly reduced. Regarding $LT{\beta}R$ signaling with a focus on MLCK inhibition, we showed that the phosphorylation of MLCs was reduced by $LT{\beta}R$ stimulation in FRCs. Cytoskeleton components, such as tubulin, b-actin, and phospho-ezrin proteins acting as membrane-cytoskeleton linkers, were produced in de-phosphorylation, and they reduced expression in agonistic anti-$LT{\beta}R$ antibody-treated FRCs. Collectively, the results suggested that MLCK and ROCK were simultaneously responsible for SF regulation triggered by $LT{\beta}R$ signaling in FRCs.

• Korean Journal of Food Science and Technology
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• v.51 no.2
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• pp.182-187
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• 2019

Women who undergo natural menopause transition have increased numbers of risk factors relating to metabolic syndrome due to estrogen deficiency. This study was conducted to investigate the effect of Superhongmi bran extract on metabolic syndrome improvement in menopausal women. Thirty women, who participated in a randomized, double-blind, placebo-controlled trial, were assigned to placebo-control (n=15) or Superhongmi bran extract (n=15) groups and were asked to consume two tablets (350 mg per extract per tablet) per day. After 12 weeks, weight, body mass index (BMI), plasma triglyceride (TG) levels, and total cholesterol (TC) levels were significantly decreased, whereas HDL-cholesterol (HDL-C), apolipoprotein A1 (ApoA1), adiponectin, superoxide dismutase 1 (SOD1), and GSH (glutathione) concentrations were significantly increased in the Superhongmi bran extract group. Moreover, $17{\beta}-estradiol$, and progesterone levels in the Superhongmi group were significantly higher than those in the placebo-control group. These results suggest that Superhongmi bran extract alleviates metabolic symptom in menopausal women.

• Biomolecules & Therapeutics
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• v.29 no.6
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• pp.685-696
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• 2021

In this study, we investigated the inhibitory effect of 5-aminolevulinic acid (ALA), a heme precursor, on inflammatory and oxidative stress activated by lipopolysaccharide (LPS) in RAW 264.7 macrophages by estimating nitric oxide (NO), prostaglandin E2 (PGE2), cytokines, and reactive oxygen species (ROS). We also evaluated the molecular mechanisms through analysis of the expression of their regulatory genes, and further evaluated the anti-inflammatory and antioxidant efficacy of ALA against LPS in the zebrafish model. Our results indicated that ALA treatment significantly attenuated the LPS-induced release of pro-inflammatory mediators including NO and PGE2, which was associated with decreased inducible NO synthase and cyclooxygenase-2 expression. ALA also inhibited the LPS-induced expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, reducing their extracellular secretion. Additionally, ALA abolished ROS generation, improved the mitochondrial mass, and enhanced the expression of heme oxygenase-1 (HO-1) and the activation of nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) in LPS-stimulated RAW 264.7 macrophages. However, zinc protoporphyrin, a specific inhibitor of HO-1, reversed the ALA-mediated inhibition of pro-inflammatory cytokines production and activation of mitochondrial function in LPS-treated RAW 264.7 macrophages. Furthermore, ALA significantly abolished the expression of LPS-induced pro-inflammatory mediators and cytokines, and showed strong protective effects against NO and ROS production in zebrafish larvae. In conclusion, our findings suggest that ALA exerts LPS-induced anti-inflammatory and antioxidant effects by upregulating the Nrf2/HO-1 signaling pathway, and that ALA can be a potential functional agent to prevent inflammatory and oxidative damage.