• Parasites, Hosts and Diseases
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• v.60 no.5
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• pp.309-315
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• 2022

Inflammatory bowel disease (IBD) is a chronic and recurrent illness of the gastrointestinal tract. Treatment of IBD traditionally involves the use of aminosalicylic acid and steroids, while these drugs has been associated with untoward effects and refractoriness. The absence of effective treatment regimen against IBD has led to the exploration of new targets. Parasites are promising as an alternative therapy for IBD. Recent studies have highlighted the use of parasite-derived substances, such as excretory secretory products, extracellular vesicles (EVs), and exosomes, for the treatment of IBD. In this report, we examined whether EVs secreted by Giardia lamblia could prevent colitis in a mouse model. G. lamblia EVs (GlEVs) were prepared from in vitro cultures of Giardia trophozoites. Clinical signs, microscopic colon tissue inflammation, and cytokine expression levels were detected to assess the effect of GlEV treatment on dextran sulfate sodium (DSS)-induced experimental murine colitis. The administration of GlEVs prior to DSS challenge reduced the expression levels of pro-inflammatory cytokines, including tumor necrosis factor alpha, interleukin 1 beta, and interferon gamma. Our results indicate that GlEV can exert preventive effects and possess therapeutic properties against DSS-induced colitis.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.3
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• pp.201-208
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• 2022

Neuroinflammation is defined as a neurological inflammation within the brain and the spinal cord. In neuroinflammation, microglia are the tissue-resident macrophages of the central nervous system, which act as the first line of defense against harmful pathogens. Dexmedetomidine (Dex) has an anti-inflammatory effect in many neurological conditions. Additionally, the microRNA-30a-5p (miR-30a-5p) mimic has been proven to be effective in macrophages in inflammatory conditions. This study aimed to investigate the synergistic anti-inflammatory effects of both miR-30a-5p and Dex in lipopolysaccharide (LPS)-induced BV2 cells. This study showed that miR-30a-5p and Dex decreased nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) translocation in LPS-induced BV2 cells. MiR-30a-5p and Dex alleviated tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), LPS-induced phosphorylation c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinase (ERK) and p38. Also, the expression of the NOD-like receptor pyrin domain containing 3 inflammasome (NLRP3), cleaved caspase-1, and ASC was inhibited. Furthermore, LPS-stimulated nitric oxide (NO) production, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) expression were attenuated by Dex and miR-30a-5p. Our results indicate that a combination of Dex and miR-30a-5p, attenuates NF-κB activation, the mitogen-activated protein kinase (MAPK) signaling pathway, and inflammatory mediators involved in LPS-induced inflammation and inhibits the activation of the NLRP3 inflammasome in LPS-activated BV2 cells.

• The Korea Journal of Herbology
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• v.37 no.5
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• pp.17-26
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• 2022

Objective : The aim of the present study is to examine hepatic lipid-lowering and anti-inflammatory effects of silymarin combined with Jakyakgamcho-tang on non-alcoholic fatty liver disease in a high fat diet-induced obese mice model. Methods : C57BL/6 mice were divided into four dietary groups: (1) Normal, (2) Control (60% high-fat diet), (3) Control + silymarin 50 mg/kg/day (Silymarin), (4) Control + Silymarin 50 mg/kg/day + Jakyakgamcho-tang 100 mg/kg/day (SPG). After 12 weeks administration, mice were sacrificed and lipids and inflammation-related biomarkers were analyzed liver and plasma. Results : Silymarin and SPG treatments significantly lowered body and liver weights compared to the Control. Serumlipids (triglyceride (TG), total cholesterol) and pro-inflammatory cytokines (tumor necrosis factor alpha, interleukin 1𝛽, and IL-6) concentrations were significantly lowered in the Silymarin and SPG groups than the Control group. Silymarin and SPG treatments suppressed hepatic TG level and hepatic lipid droplets compared to the Control. Theses two treatments significantly increased hepatic kinase B1 and AMP-activated protein kinase protein levels, and significantly decreased hepatic key lipogenic enzymes (acetyl-CoA carboxylase, fatty acid synthase and stearyl coenzyme A desaturase 1) protein levels than the Control. SPG also significantly increased hepatic fatty acid oxidation-related protein (peroxisome proliferator-activated receptor alpha and uncoupling protein 2) levels than the Control. Conclusions: Silymarin and SPG suppressed hepatic lipid accumulation by regulating hepatic protein expression, and lowered blood pro-inflammatory cytokines concentrations though the synergic effect of silymarin and Jakyakgamchotang was not clear.

• BMB Reports
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• v.54 no.5
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• pp.278-283
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• 2021

Our understanding of the differential effects between specific omega-3 fatty acids is incomplete. Here, we aimed to evaluate the effects of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on T-helper type 1 (Th1) cell responses and identify the pathways associated with these responses. Naïve CD4⁺ T cells were co-cultured with bone marrow-derived dendritic cells (DCs) in the presence or absence of palmitate (PA), DHA, or EPA. DHA or EPA treatment lowered the number of differentiated IFN-γ-positive cells and inhibited the secretion of IFN-γ, whereas only DHA increased IL-2 and reduced TNF-α secretion. There was reduced expression of MHC II on DCs after DHA or EPA treatment. In the DC-independent model, DHA and EPA reduced Th1 cell differentiation and lowered the cell number. DHA and EPA markedly inhibited IFN-γ secretion, while only EPA reduced TNF-α secretion. Microarray analysis identified pathways involved in inflammation, immunity, metabolism, and cell proliferation. Moreover, DHA and EPA inhibited Th1 cells through the regulation of diverse pathways and genes, including Igf1 and Cpt1a. Our results showed that DHA and EPA had largely comparable inhibitory effects on Th1 cell differentiation. However, each of the fatty acids also had distinct effects on specific cytokine secretion, particularly according to the presence of DCs.

• Journal of Animal Science and Technology
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• v.64 no.6
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• pp.1117-1131
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• 2022

Previous studies reported that Bifidobacterium animalis ssp. lactis HY8002 (HY8002) improved intestinal integrity and had immunomodulatory effects. Lactobacillus plantarum HY7717 (HY7717) was screened in vitro from among 21 other lactic acid bacteria (LAB) and demonstrated nitric oxide (NO) production. The aims of this study were to investigate the individual and combined ex vivo and in vivo effects of LAB strains HY8002 and HY7717 at immunostimulating mice that have been challenged with an immunosuppressant drug. The combination of HY8002 and HY7717 increased the secretion of cytokines such as interferon (IFN)-γ, interleukin (IL)-12, and tumor necrosis factor (TNF)-α in splenocytes. In a cyclophosphamide (CTX)-induced immunosuppression model, administration of the foregoing LAB combination improved the splenic and hematological indices, activated natural killer (NK) cells, and up-regulated plasma immunoglobulins and cytokines. Moreover, this combination treatment increased Toll-like receptor 2 (TLR2) expression. The ability of the combination treatment to upregulate IFN-γ and TNF-α in the splenocytes was inhibited by anti-TLR2 antibody. Hence, the immune responses stimulated by the combination of HY8002 and HY7717 are associated with TLR2 activation. The preceding findings suggest that the combination of the HY8002 and HY7717 LAB strains could prove to be a beneficial and efficacious immunostimulant probiotic supplement. The combination of the two probiotic strains will be applied on the dairy foods including yogurt and cheese.

• The Korea Journal of Herbology
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• v.27 no.6
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• pp.55-61
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• 2012

Objectives : Allium Hookeri (AH) is a traditional herb to treat inflammatory diseases in India and Myanmar. Recently, AH cultivation was succeeded in South Korea. This study was performed to evaluate the anti-inflammatory effects of Korean AH in RAW264.7 cells, mouse macrophage cell line. Methods : To evaluate the anti-inflammatory effects of root of AH, we prepared the 70% ethanol extract, then we examined the productions of nitrite, and pro-inflammatory cytokines. To examine the nitrite, and cytokines, the RAW264.7 cells were treated with AH, then stimulated with lipopolysaccharide (LPS, 500 ng/ml) for 24 h. Then the cells were harvested for griess assay, ELISA and real-time reverse transcription polymerase chain reaction (RT-PCR). Also to detect the ability of AH to induce heme oxygenase-1 (HO-1), we examined the HO-1 expression using real time RT-PCR and western blot. Furthermore, we examined the mitogen activated-protein kinases (MAPKs) and nuclear factor kappa B (NF-${\kappa}B$) activation to find out the underlying mechanisms. Results : AH ethanol extract significantly inhibited the productions of nitrite and interleukin (IL)-$1{\beta}$. AH treatment increased the HO-1 expression dramatically at 1 h, then peaked at 3 h. When the HO-1 was inhibited by tin (Sn) protoporphryin-IX (SnPP), the anti-inflammatory action of AH was reversed. AH treatment inhibited the activation of p38, but not extracelluar signal-regulated kinase (ERK 1/2) and c-Jun $NH_2$-terminal kinase (JNK) and also the degradation of inhibitory kappa B a (Ik-$B{\alpha}$) in the LPS-stimulated RAW 264.7 cells. Conclusions : These data could suggest that AH exerts anti-inflammatory influences through up-regulation of HO-1 and deactivation of p38.

• The Korea Journal of Herbology
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• v.34 no.6
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• pp.117-124
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• 2019

Objective : Broccoli is edible green plant that has a wide variety of health benefits including cancer prevention and cholesterol reduction. However, leaves of broccoli are not eaten and are mostly left as waste. This study was conducted to evaluate the effects of the broccoli leaf extract (BLE) on prostaglandin E₂ (PGE₂) production related to nuclear factor kappa B (NF-κB) signaling in lipopolysaccharide (LPS)-activated macrophages. Methods : BLE was prepared by extracting dried leaf with ethanol. Cell viability was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. PGE₂ and inflammatory cytokines were detected by enzyme-linked immunosorbent assay (ELISA). Expression level of each protein was monitored by Western blot analysis. Results : In LPS-activated Raw264.7 cells, PGE₂ release into culture medium was dramatically enhanced compared to control cells. However, increased PGE₂ was attenuated dose-dependently by treatment with BLE. Inhibition of PGE₂ production by BLE was due to the suppression of cyclooxygenase-2 (COX-2) expression determined by Western blot analysis. BLE also inhibited the production of inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Inhibition at PGE₂ and cytokine was mediated from inhibition of nuclear translocation of NF-κB due to the repression of inhibitory kappa B alpha (IκBα) phosphorylation and degradation. Conclusion : This study showed that BLE exerted inhibitory activities against PGE₂, which is critical for the initiation and resolution of inflammatory responses, and that inhibition of PGE₂ was mediated by suppression of NF-κB signaling. These results suggest that the waste broccoli leaves could be used for controlling inflammation.

• Korean Journal of Exercise Nutrition
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• v.25 no.1
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• pp.42-55
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• 2021

[Purpose] This study investigated the effects of marine phytoplankton supplementation (Oceanix®, Tetraselmis chuii) on 1) maximal isometric strength and immune function in healthy humans following a oneweek high-intensity resistance-training program and 2) the proinflammatory cytokine response to exercise in a rat model. [Methods] In the human trial, 22 healthy male and female participants were randomly divided into marine phytoplankton and placebo groups. Following baseline testing, participants underwent a 14-day supplement loading phase before completing five consecutive days of intense resistance training. In the rat model, rats were randomly divided into four groups (n=7 per condition): (i) control, (ii) exercise, (iii) exercise + marine phytoplankton (2.55 mg/kg/day), or (iv) exercise + marine phytoplankton (5.1 mg/kg/day). Rats in the exercising groups performed treadmill exercise 5 days per week for 6 weeks. [Results] In the human model, marine phytoplankton prevented significant declines in the isometric peak rate of force development compared to placebo. Additionally, salivary immunoglobulin A concentration was significantly lower following the resistance training protocol in the placebo group but not in the marine phytoplankton group. Marine phytoplankton in exercising rats decreased intramuscular levels and serum concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) and intramuscular concentrations of malondialdehyde. [Conclusion] Marine phytoplankton prevented decrements in indices of functional exercise recovery and immune function. Mechanistically, these outcomes could be prompted by modulating the oxidative stress and proinflammatory cytokine response to exercise.

• Biomolecules & Therapeutics
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• v.31 no.2
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• pp.161-167
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• 2023

Despite the various medications used in clinics, the efforts to develop more effective treatments for depression continue to increase in the past decades mainly because of the treatment-resistant population, and the testing of several hypotheses- and target-based treatments. Undesirable side effects and unresponsiveness to current medications fuel the drive to solve this top global health problem. In this study, we focused on neuroinflammatory response-mediated depression which represents a cluster of depression etiology both in animal models and humans. Several meta-analyses reported that proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were increased in major depressive disorder patients. Inflammatory mediators implicated in depression include type-I interferon and inflammasome pathways. To elucidate the molecular mechanisms of neuroinflammatory cascades underlying the pathophysiology of depression, we introduced hycanthone, an antischistosomal drug, to check whether it can counteract depressive-like behaviors in vivo and normalize the inflammation-induced changes in vitro. Lipopolysaccharide (LPS) treatment increased proinflammatory cytokine expression in the murine microglial cells as well as the stimulation of type I interferon-related pathways that are directly or indirectly regulated by Janus kinase-signal transducer and activator of transcription (JAK-STAT) activation. Hycanthone treatment attenuated those changes possibly by inhibiting the JAK-STAT pathway and inflammasome activation. Hycanthone also ameliorated depressive-like behaviors by LPS. Taken together, we suggest that the inhibitory action of hycanthone against the interferon pathway leading to attenuation of depressive-like behaviors can be a novel therapeutic mechanism for treating depression.

• Journal of Ginseng Research
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• v.47 no.2
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• pp.291-301
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• 2023

Introduction: Non-small cell lung cancer (NSCLC) patients are particularly vulnerable to the Coronavirus Disease-2019 (COVID-19). Currently, no anti-NSCLC/COVID-19 treatment options are available. As ginsenoside Rg3 is beneficial to NSCLC patients and has been identified as an entry inhibitor of the virus, this study aims to explore underlying pharmacological mechanisms of ginsenoside Rg3 for the treatment of NSCLC patients with COVID-19. Methods: Based on a large-scale data mining and systemic biological analysis, this study investigated target genes, biological processes, pharmacological mechanisms, and underlying immune implications of ginsenoside Rg3 for NSCLC patients with COVID-19. Results: An important gene set containing 26 target genes was built. Target genes with significant prognostic value were identified, including baculoviral IAP repeat containing 5 (BIRC5), carbonic anhydrase 9 (CA9), endothelin receptor type B (EDNRB), glucagon receptor (GCGR), interleukin 2 (IL2), peptidyl arginine deiminase 4 (PADI4), and solute carrier organic anion transporter family member 1B1 (SLCO1B1). The expression of target genes was significantly correlated with the infiltration level of macrophages, eosinophils, natural killer cells, and T lymphocytes. Ginsenoside Rg3 may benefit NSCLC patients with COVID-19 by regulating signaling pathways primarily involved in anti-inflammation, immunomodulation, cell cycle, cell fate, carcinogenesis, and hemodynamics. Conclusions: This study provided a comprehensive strategy for drug discovery in NSCLC and COVID-19 based on systemic biology approaches. Ginsenoside Rg3 may be a prospective drug for NSCLC patients with COVID-19. Future studies are needed to determine the value of ginsenoside Rg3 for NSCLC patients with COVID-19.