• Journal of Physiology & Pathology in Korean Medicine
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• v.32 no.6
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• pp.396-402
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• 2018

Hataedock (HTD) treatment is a traditional preventive therapy for the fetal toxicosis- the acute allergic disease after childbirth, mainly manifested by a variety of skin allergies such as scab, phlegm. The aim of this study was to investigate the efficacy of HTD treatments for the alleviation of inflammation in Dermatophagoides farinae-induced obese NC/Nga mice. 20 mg/kg of Coptidis Rhizoma, Glycyrrhizae Radix (CRGR) extracts as a remedy of HTD treatments were orally administered to NC/Nga mice. We induced obesity in the mice by high-fat diet. To induce skin allergies, the extracts of Dermatophagoides farinae were topically applied on the NC/Nga mice at 4th-6th and 8th-10th weeks. Structural and molecular changes in the skin tissues were measured by immunohistochemical staining. HTD treatment decreased the atopic dermatitis (AD)-like symptoms including hemorrhage, erythema, erosion, edema, and dryness. HTD treatment suppressed the mast cell activation confirmed by reduction of $Fc{\varepsilon}RI$, substance P, and serotonin. The expression of several inflammatory mediators including nuclear factor-kappa B ($NF-{\kappa}B$) p65, inducible nitric oxide synthase (iNOS), vascular endothelial growth factors (VEGFs) was also decreased by HTD treatment. HTD treatment suppressed the allergic, inflammatory responses in the skin tissues of the NC/Nga mice by reducing mast cells and down-regulating several inflammatory mediators.

• Korean Journal of Plant Resources
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• v.31 no.6
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• pp.612-621
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• 2018

Honey used as conventional medicine has various pharmacological properties. In the honey and anti-inflammatory effect, Gelam honey and Manuka honey has been reported to exert anti-inflammatory activity. However, the anti-inflammatory effect and potential mechanisms of acacia honey (AH) are not well understood. In this study, we investigated anti-inflammatory activity and mechanism of action of AH in LPS-stimulated RAW264.7 cells. AH attenuated NO production through inhibition of iNOS expression in LPS-stimulated RAW264.7 cells. AH also decreased the expressions of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ as pro-inflammatory cytokines, and MCP-1 expression as a pro-inflammatory chemokine. In the elucidation of the molecular mechanisms, AH decreased LPS-mediated $I{\kappa}B$-${\alpha}$ degradation and subsequent nuclear accumulation of p65, which resulted in the inhibition of $NF-{\kappa}B$ activation in RAW264.7 cells. AH dose-dependently suppressed LPS-mediated phosphorylation of ERK1/2 and p38 in RAW264.7 cells. In addition, AH significantly inhibited ATF2 phosphorylation and nuclear accumulation of ATF2 in LPS-stimulated RAW264.7 cells. These results suggest that AH has an anti-inflammatory effect, inhibiting the production of pro-inflammatory mediators such as NO, iNOS, $TNF-{\alpha}$, IL-6, $IL-1{\beta}$ and MCP-1 via interruption of the $NF-{\kappa}B$ and MAPK/ATF2 signaling pathways.

• The Journal of Pediatrics of Korean Medicine
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• v.33 no.2
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• pp.22-31
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• 2019

Objective This study is to learn the effects of Hataedock method using Coptidis rhizoma and Glycyrrhiza uralensis mixed extract on inflammatory response in allergic rhinitis-induced obese NC/Nga mice. Materials and Methods The mice were fed with high fat-diet to be obese, and were divided into 3 groups as follows; allergic rhinitis-induced obese mice group with Hataedock method (CGT, n=10), no treatment group (Ctrl), allergic rhinitis elicited obese mice group (ARE). To induce allergic rhinitis, NC/Nga mice of 3 weeks age were sensitized on 7, 8 and 9 weeks by ovalbumin antigen in intraperitoneal space. After 7 days of final sensitization, allergic rhinitis was initially induced in mice through nasal cavities for 5 days. After 1-week, allergic rhinitis was induced again by the same method. Histological examination was used to identify distribution of IL-4, CD40, STAT6, $Fc{\varepsilon}RI$, substance P, MMP-9, NF-${\kappa}B$ p65, iNOS and COX-2. Results Hataedock method significantly reduced IL-4, STAT6 and CD40 response (p<0.05). In CGT, the inhibition of Th2 differentiation decreased inflammatory mediators such as $Fc{\varepsilon}RI$, substance P, MMP-9, NF-${\kappa}B$ p65, iNOS and COX-2 (all p<0.05). The immunological improvement led reduction of respiratory epithelial damage and mucin secretion in goblet cell. Conclusion The results of this study show that the Hataedock method suppresses the expression of allergic rhinitis by decreasing the inflammatory mediators through the regulation of Th2 differentiation even when the inflammation reaction is increased by obesity. Therefore, Hataedock may have potential preventive measure of allergic rhinitis accompanied by obese.

• Korean Journal of Agricultural Science
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• v.48 no.3
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• pp.607-615
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• 2021

Cytokines are protein mediators that possess the ability to assist cell-to-cell communication in immune system-related activities. In general, pathogen endotoxins activate the release of inflammatory mediators, and with time, there is an increase in the cytokine levels in the body. Interleukin (IL)-6 mediates the acute-phase inflammatory response, and elevated IL-6 levels have been reported in peritoneal fluids of women with pelvic inflammation and endometriosis, thereby associating it with oocyte quality and infertility. To overcome subfertility or infertility in humans and animals, the present study was done to examine the effect of recombinant IL-6 on porcine oocytes matured in vitro and subsequently to determine the fertilization rate and embryo development. Porcine oocytes were incubated with varying concentrations of IL-6 (0 - 2 ㎍·mL^-1) for 44 h followed by in vitro fertilization and culturing of the oocytes. The oocytes or embryos were fixed with 3.7% paraformaldehyde (PFA) and stained with fluorescence dyes, and the meiotic spindle, chromosome organization, fertilization status and embryo development were subsequently assessed under a fluorescence microscope. We observed induction of an abnormal meiotic spindle alignment in the oocytes incubated with IL-6 compared to the control oocytes incubated without IL-6. Moreover, significantly decreased fertilization rates and embryo development were observed for oocytes incubated with IL-6 (p < 0.05). Thus, an increased IL-6 level during oocyte maturation could be associated with fertilization failure due to an aberrant chromosomal alignment and a disruption of the cortical granules. Taken together, our results indicate that successful assisted reproduction can be achieved by controlling the levels of inflammatory cytokines.

• The Korea Journal of Herbology
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• v.36 no.1
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• pp.67-76
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• 2021

Objective : Yukgunja-tang is one of the herbal prescriptions widely used for functional indigestion. In this study, we evaluated the pharmacological effect through the Yukgunja-tang formulation development. Methods : The RAW 264.7 cells were pretreated with Yukgunja-tang tablet (YGJT-T : 50, 100 and 200 ㎍/㎖) and then stimulated with lipopolysaccharide (LPS : 500 ng/㎖). Cell viability, inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2) and inflammatory cytokines (IL-1β, IL-6, and TNF-α) were measured. Also, ICR mice induced acute gastritis by oral administration of 150 mM HCl in 60% ethanol. The YGJT-T (30 mg/kg) was pretreated for 3 days, and 150 mM HCl in 60% ethanol was orally administered 1 hour after the last drug treatment. Mice were sacrificed 1 hour after oral administration of 150 mM HCl in 60% ethanol. The gastric mucosa was observed, and inflammatory cytokines in the gastric tissue were measured. Results : The marker components of YGJT-T were determined by simultaneous analysis using HPLC. In RAW 264.7 cells, pretreatment of YGJT-T was non-toxic and inhibited the production of inflammatory mediators such as NO and PGE2 and suppressed inflammatory cytokines. In addition, pretreatment of YGJT-T improved bleeding and edema due to gastric lesions caused by acute gastritis and suppressed inflammatory cytokines. Conclusion : In summary, our results confirmed that treatment with YGJT-T has anti-inflammatory and anti-gastritis effects in vitro and in vivo. Therefore, in this study, YGJT-T could support a potential strategy for the prevention and treatment of gastritis.

• Journal of Ginseng Research
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• v.45 no.4
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• pp.510-518
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• 2021

Background: Gintonin is a newly derived glycolipoprotein from the roots of ginseng. The purpose of this study is to investigate the anti-arthritic efficacy of Gintonin on various proteases and inflammatory mediators that have an important role in arthritis. Methods: Fibroblast-like synoviocytes (FLS) were treated with Gintonin and stimulated with interleukin (IL)-1β 1 hour later. The antioxidant effect of Gintonin was measured using MitoSOX and H₂DCFDA experiments. The anti-arthritic efficacy of Gintonin was examined by analyzing the expression levels of inflammatory mediators using RT-PCR, western blot, and ELISA. The phosphorylation of mitogen-activated protein kinase (MAPK) pathways and translocation of nuclear factor kappa B (NF-κB)/p65 into the nucleus were also analyzed using western blot, ELISA, and immunocytochemistry. Collagen-induced arthritis (CIA) mice model was used. Mice were orally administered with Gintonin (25, 50, and 100 mg/kg) every 2 days for 45 days. The body weight, arthritis score, squeaking score, and paw volume were measured as the behavioral parameters. After sacrifice, H&E and safranin-O staining were performed for histological analysis. Results: Gintonin significantly inhibited the expression of inflammatory intermediates. Gintonin prevented NF-κB/p65 from moving into the nucleus through the JNK and ERK MAPK phosphorylation in FLS cells. Moreover, Gintonin suppressed the symptoms of arthritis in the CIA mice model. Conclusion: As a result, the antioxidant and anti-inflammatory effects of Gintonin were demonstrated, and ultimately the anti-arthritic effect was proved. Collectively, Gintonin has a great potential as a therapeutic agent for arthritis treatment.

• Biomolecules & Therapeutics
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• v.29 no.2
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• pp.144-153
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• 2021

Astrocytes play various important roles such as maintaining brain homeostasis, supporting neurons, and secreting inflammatory mediators to protect the brain cells. In aged subjects, astrocytes show diversely changed phenotypes and dysfunctions. But, the study of aged astrocytes or astrocytes from aged subjects is not yet sufficient to provide a comprehensive understanding of their important processes in the regulation of brain function. In this study, we induced an in vitro aged astrocyte model through late passage cultivation of rat primary cultured astrocytes. Astrocytes were cultured until passage 7 (P7) as late passage astrocytes and compared with passage 1 (P1) astrocytes as early passage astrocytes to confirm the differences in phenotypes and the effects of serial passage. In this study, we confirmed the morphological, molecular, and functional changes of late passage astrocytes showing aging phenotypes through SA-β-gal staining and measurement of nuclear size. We also observed a reduced expression of inflammatory mediators including IL-1β, IL-6, TNFα, iNOS, and COX2, as well as dysregulation of wound-healing, phagocytosis, and mitochondrial functions such as mitochondrial membrane potential and mitochondrial oxygen consumption rate. Culture-conditioned media obtained from P1 astrocytes promoted neurite outgrowth in immature primary cultures of rat cortices, which is significantly reduced when we treated the immature neurons with the culture media obtained from P7 astrocytes. These results suggest that late passage astrocytes show senescent astrocyte phenotypes with functional defects, which makes it a suitable model for the study of the role of astrocyte senescence on the modulation of normal and pathological brain aging.

• The Journal of Pediatrics of Korean Medicine
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• v.35 no.1
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• pp.76-103
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• 2021

Objectives This study was designed to examine the effect of Gleditsiae Fructus n-hexane (GSF_Hx) on two different groups (on the LPS-induced activation of Raw264.7 cells in vitro, and on the DNCB-induced activation of atopic dermatitis NC/Nga Tnd mice in vivo) to find index components and active components of Gleditsiae Fructus. Methods GSF_Hx was analyzed by HPLC profiling and confirmed echinocystic acid (EA), oleanolic acid (OA) as index components of Gleditsiae Fructus. Using GSF_Hx, EA, OA, we investigated IL-6, TNF-α, NO production by ELISA analysis and evaluated manifestations of MAPKs transcription factors and NF-κB p65 translocation by western blotting. During In vivo study, atopic dermatitis was induced on NC/Nga Tnd mice by DNCB and administered GSF_Hx, EA, OA orally, and checked skin lesions and measured skin clinical score. Serum IgE level, Th1 and Th2 cytokines secretion and modulating molecular mediators and immune cells in the spleenocyte culture supernatant, PBMCs, ALN and dorsal skin were also measured by real-time PCR. Then, skin rash was evaluated and mast cell distribution was verified by H&E and toluidine blue staining on dorsal skin. Results It is possible that GSF_Hx, EA and OA reduce inflammation and allergic response of atopic dermatitis by suppressing Th1 and Th2 cytokines secretion and modulating molecular mediators and immune cells. They also had moisturizing effect by raising vitality of ceramide in dorsal skin of atopic dermatitis NC/Nga Tnd mice. However, EA particularly had better overall activity data than OA, that EA could be a more effective active component of Gleditsiae Fructus than OA. Conclusions Based on the inflammatory reduction property with moisturizing effect, GSF_Hx may play a role in effective treatment for atopic dermatitis.

• Journal of Arbitration Studies
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• v.32 no.1
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• pp.71-91
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• 2022

The legal integration in the European Union that seeks a unified system in consumer disputes and the German Consumer Dispute Mediation Act based on this pursues the procedural fairness of consumer disputes and the equality of results. The role and legal status of the dispute mediator, who plays a very important role in this process, and the stable operation of the dispute resolution system and the guarantee of reasonable results through the guarantee of fairness and independence are very important values. In particular, the dispute mediator under the Act is conceptually different from the existing mediator or mediator, and through this distinction, the duties and contents of the dispute mediator are also distinguished. For this reason, the qualifications of dispute mediators that affect the outcome of dispute mediation are strictly stipulated. There have been some criticisms of this strictness, and such strictness is also seen as an excessive limitation. However, these standards can be understood as one of the efforts to make the dispute mediation procedure more systematic and to operate objectively in accordance with laws and procedures. In addition, in relation to the issue of independence and impartiality of the dispute mediator, the status of the dispute mediator is guaranteed in various aspects. In economic terms, it is not influenced by external factors, and furthermore, in order to guarantee job stability, the results of job security and dispute resolution are not linked. By examining the appropriate level of discipline for these dispute mediators, we expect the developmental growth of the consumer dispute resolution system under our Act.

• BMB Reports
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• v.55 no.8
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• pp.370-379
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• 2022

Human pregnancy is a delicate and complex process where multiorgan interactions between two independent systems, the mother, and her fetus, maintain pregnancy. Intercellular interactions that can define homeostasis at the various cellular level between the two systems allow uninterrupted fetal growth and development until delivery. Interactions are needed for tissue remodeling during pregnancy at both fetal and maternal tissue layers. One of the mechanisms that help tissue remodeling is via cellular transitions where epithelial cells undergo a cyclic transition from epithelial to mesenchymal (EMT) and back from mesenchymal to epithelial (MET). Two major pregnancy-associated tissue systems that use EMT, and MET are the fetal membrane (amniochorion) amnion epithelial layer and cervical epithelial cells and will be reviewed here. EMT is often associated with localized inflammation, and it is a well-balanced process to facilitate tissue remodeling. Cyclic transition processes are important because a terminal state or the static state of EMT can cause accumulation of proinflammatory mesenchymal cells in the matrix regions of these tissues and increase localized inflammation that can cause tissue damage. Interactions that determine homeostasis are often controlled by both endocrine and paracrine mediators. Pregnancy maintenance hormone progesterone and its receptors are critical for maintaining the balance between EMT and MET. Increased intrauterine oxidative stress at term can force a static (terminal) EMT and increase inflammation that are physiologic processes that destabilize homeostasis that maintain pregnancy to promote labor and delivery of the fetus. However, conditions that can produce an untimely increase in EMT and inflammation can be pathologic. These tissue damages are often associated with adverse pregnancy complications such as preterm prelabor rupture of the membranes (pPROM) and spontaneous preterm birth (PTB). Therefore, an understanding of the biomolecular processes that maintain cyclic EMT-MET is critical to reducing the risk of pPROM and PTB. Extracellular vesicles (exosomes of 40-160 nm) that can carry various cargo are involved in cellular transitions as paracrine mediators. Exosomes can carry a variety of biomolecules as cargo. Studies specifically using exosomes from cells undergone EMT can carry a pro-inflammatory cargo and in a paracrine fashion can modify the neighboring tissue environment to cause enhancement of uterine inflammation.