• Herbal Formula Science
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• v.29 no.3
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• pp.127-145
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• 2021

Objectives : The purpose of this study was to evaluate the effects of Daeganghwal-tang on knee cartilage in monosodium iodoacetate(MIA)-induced osteoarthritis rats. Methods : Forty SD rats were randomly divided into five groups(n=8/group): normal group was SD rats group injected with normal saline at left knee joint and administrated orally distilled water, control group was MIA-induced osteoarthritis SD rats group administrated orally distilled water, Indomethacin group was MIA-induced osteoarthritis SD rats group administrated orally indomethacin 2 mg/kg, DGHT(L) group was MIA-induced osteoarthritis SD rats group administrated orally 1280 mg/kg of Daeganghwal-tang, and DGHT(H) group was MIA-induced osteoarthritis SD rats group administrated orally 2560 mg/kg of Daeganghwal-tang. After orally administration of drugs for 4 weeks, gross appearance and histological analysis were used to evaluate the degree of knee cartilage damage. In addition, pro-inflammatory cytokines, bone degrade factor and bone defence factors were analyzed to investigate the anti-inflammatory and cartilage protection effects of Daeganghwal-tang. Also, hematological test, biochemical test, and liver and kidney tissue were analyzed to determine the safety of Daeganghwal-tang. Results : Daeganghwal-tang inhibited the damage of the knee cartilage, and significantly prevented the reduction in cartilage thickness. In addition, the pro-inflammatory cytokines and the bone degrade factor significantly decreased, and the bone defence factors significantly increased. In the safety assessment of Daeganghwal-tang, there were no significant differences among the experimental groups and no abnormal findings were observed. Conclusions : Daeganghwal-tang has anti-inflammatory effect, inhibits cartilage damage, and protects cartilage in MIA-induced osteoarthritis rats.

• Nutrition Research and Practice
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• v.15 no.6
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• pp.686-702
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• 2021

BACKGROUND/OBJECTIVES: Schisandrae Fructus, the fruit of Schisandra chinensis Baill., has traditionally been used as a medicinal herb for the treatment of various diseases, and has proven its various pharmacological effects, including anti-inflammatory and antioxidant activities. In this study, we investigated the inhibitory effect of Schisandrae Fructus ethanol extract (SF) on inflammatory and oxidative stress in particulate matter 2.5 (PM2.5)-treated RAW 264.7 macrophages. MATERIALS/METHODS: To investigate the anti-inflammatory and antioxidant effects of SF in PM2.5-stimulated RAW 264.7 cells, the levels of pro-inflammatory mediator such as nitric oxide (NO) and prostaglandin E₂ (PGE₂), cytokines including interleukin (IL)-6 and IL-1β, and reactive oxygen species (ROS) were measured. To elucidate the mechanism underlying the effect of SF, the expression of genes involved in the generation of inflammatory factors was also investigated. We further evaluated the anti-inflammatory and antioxidant efficacy of SF against PM2.5 in the zebrafish model. RESULTS: The results indicated that SF treatment significantly inhibited the PM2.5-induced release of NO and PGE₂, which was associated with decreased inducible NO synthase and cyclooxygenase-2 expression. SF also attenuated the PM2.5-induced expression of IL-6 and IL-1β, reducing their extracellular secretion. Moreover, SF suppressed the PM2.5-mediated translocation of nuclear factor-kappa B (NF-κB) from the cytosol into nuclei and the degradation of inhibitor IκB-α, indicating that SF exhibited anti-inflammatory effects by inhibiting the NF-κB signaling pathway. In addition, SF abolished PM2.5-induced generation of ROS, similar to the pretreatment of a ROS scavenger, but not by an inhibitor of NF-κB activity. Furthermore, SF showed strong protective effects against NO and ROS production in PM2.5-treated zebrafish larvae. CONCLUSIONS: Our findings suggest that SF exerts anti-inflammatory and antioxidant effects against PM2.5 through ROS-dependent down-regulating the NF-κB signaling pathway, and that SF can be a potential functional substance to prevent PM2.5-mediated inflammatory and oxidative damage.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.6
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• pp.533-543
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• 2021

Myocardial fibrosis (MF) is the result of persistent and repeated aggravation of myocardial ischemia and hypoxia, leading to the gradual development of heart failure of chronic ischemic heart disease. Triptolide (TPL) is identified to be involved in the treatment for MF. This study aims to explore the mechanism of TPL in the treatment of MF. The MF rat model was established, subcutaneously injected with isoproterenol and treated by subcutaneous injection of TPL. The cardiac function of each group was evaluated, including LVEF, LVFS, LVES, and LVED. The expressions of ANP, BNP, inflammatory related factors (IL-1β, IL-18, TNF-α, MCP-1, VCAM1), NLRP3 inflammasome factors (NLRP3, ASC) and fibrosis related factors (TGF-β1, COL1, and COL3) in rats were dete cted. H&E staining and Masson staining were used to observe myocardial cell inflammation and fibrosis of rats. Western blot was used to detect the p-P65 and t-P65 levels in nucleoprotein of rat myocardial tissues. LVED and LVES of MF group were significantly upregulated, LVEF and LVFS were significantly downregulated, while TPL treatment reversed these trends; TPL treatment downregulated the tissue injury and improved the pathological damage of MF rats. TPL treatment downregulated the levels of inflammatory factors and fibrosis factors, and inhibited the activation of NLRP3 inflammasome. Activation of NLRP3 inflammasome or NF-κB pathway reversed the effect of TPL on MF. Collectively, TPL inhibited the activation of NLRP3 inflammasome by inhibiting NF-κB pathway, and improved MF in MF rats.

• The Korea Journal of Herbology
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• v.33 no.3
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• pp.45-53
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• 2018

Objectives : In cases of osteoarthritis, the hypofunction of the cartilage and joint leads to a limited range of joint motion, swelling, and pain, which is generally treated using pharmaceutical drugs (e.g., anti-inflammatory agents, cartilage protectants, and nonsteroidal anti-inflammatory drugs) or replacement arthroplasty. However, long-term drug treatment is associated with adverse effects on the gastrointestinal systems. The present study aimed to evaluate the ability of Giheolsotong-hwan to treat of osteoarthritis symptoms in the MIA-induced rat model based on histological analysis, and factors that are associated with inflammation and bone mineral metabolism. Methods : Giheolsotong-hwan was administered orally at doses of 200 mg/kg/day or 400 mg/kg/day for 2 weeks before direct injection of monosodium iodoacetate ($3mg/50{\mu}{\ell}$ of 0.9% saline) into the intra-articular space of the rats' right knee. The rats subsequently received the same doses of oral Giheolsotong-hwan for another 4 weeks. We evaluated the treatment effects based on serum biomarkers and histopathological analysis of the knee joints. Results : Compared to those in control rats, the Giheolsotong-hwan treatments significantly decreased the serum concentration of inflammation factors (i.e., $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, $PGE_2$, and $LTB_4$), and bone degrade factors (i.e., MMP-9, CTX-II, and COMP). In addition, the Giheolsotong-hwan treatments significantly increased the concentration of glycosaminoglycans of bone defence factors, but no chage the TIMP-1. Furthermore, the Giheolsotong-hwan treatments effectively preserved the knee cartilage and proteoglycan. Conclusion : The results indicate that Giheolsotong-hwan treated osteoarthritis symptoms. Thus, Giheolsotong-hwan may be a novel oriental therapeutic option for the management of osteoarthritis.

• Korean Journal of Exercise Nutrition
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• v.24 no.3
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• pp.25-31
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• 2020

[Purpose] Epidemiological evidence has shown that leisure-time physical activity and structured exercise before and after breast cancer diagnosis contribute to reducing the risk of breast cancer recurrence and mortality. Thus, in this review, we aimed to summarize the physical activity-dependent regulation of systemic factors to understand the biological and molecular mechanisms involved in the initiation, progression, and survival of breast cancer. [Methods] We systematically reviewed the studies on 1) the relationship between physical activity and the risk of breast cancer, and 2) various systemic factors induced by physical activity and exercise that are potentially linked to breast cancer outcomes. To perform this literature review, PubMed database was searched using the terms "Physical activity OR exercise" and "breast cancer", until August 5th, 2020; then, we reviewed those articles related to biological mechanisms after examining the resulting search list. [Results] There is strong evidence that physical activity reduces the risk of breast cancer, and the protective effect of physical activity on breast cancer has been achieved by long-term regulation of various circulatory factors, such as sex hormones, metabolic hormones, inflammatory factors, adipokines, and myokines. In addition, physical activity substantially alters wholebody homeostasis by affecting numerous other factors, including plasma metabolites, reactive oxygen species, and microRNAs as well as exosomes and gut microbiota profile, and thereby every cell and organ in the whole body might be ultimately affected by the biological perturbation induced by physical activity and exercise. [Conclusion] The understanding of integrative mechanisms will enhance how physical activity can ultimately influence the risk and prognosis of various cancers, including breast cancer. Furthermore, physical activity could be considered an efficacious non-pharmacological therapy, and the promotion of physical activity is probably an effective strategy in primary cancer prevention.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.2
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• pp.183-189
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• 2015

Foeniculum vulgare Mill. (fennel) is used to flavor food, in cosmetics, as an antioxidant, and to treat microbial, diabetic and common inflammation. No study to date, however, has assessed the anti-inflammatory effects of fennel in experimental models of inflammation. The aims of this study were to investigate the anti-inflammatory effects of fennel in model of lipopolysaccharide (LPS)-induced acute lung injury. Mice were randomly assigned to seven groups (n=7~10). In five groups, the mice were intraperitoneally injected with 1% Tween 80-saline (vehicle), fennel (125, 250, $500{\mu}l/kg$), or dexamethasone (1 mg/kg), followed 1 h later by intratracheal instillation of LPS (1.5 mg/kg). In two groups, the mice were intraperitoneally injected with vehicle or fennel ($250{\mu}l/kg$), followed 1 h later by intratracheal instillation of sterile saline. Mice were sacrificed 4 h later, and bronchoalveolar lavage fluid (BALF) and lung tissues were obtained. Fennel significantly and dose-dependently reduced LDH activity and immune cell numbers in LPS treated mice. In addition fennel effectively suppressed the LPS-induced increases in the production of the inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, with $500{\mu}l/kg$ fennel showing maximal reduction. Fennel also significantly and dose-dependently reduced the activity of the proinflammatory mediator matrix metalloproteinase 9 and the immune modulator nitric oxide (NO). Assessments of the involvement of the MAPK signaling pathway showed that fennel significantly decreased the LPS-induced phosphorylation of ERK. Fennel effectively blocked the inflammatory processes induced by LPS, by regulating pro-inflammatory cytokine production, transcription factors, and NO.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.23 no.2
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• pp.125-138
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• 2010

Objective : The present study was examined to evaluate the effects of Ecliptae Herba on the production of inflammatory mediators in vivo and in vitro. Methods : In cell viability, all three doses of Ecliptae Herba extract (25, 50 and $100\;{\mu}g/ml$) had no significant cytotoxicity during the experimental period. The increases of NO production and iNOS expression were detected in LPS-activated cells compared to control, but these increases were dose-dependently attenuated by pre-treatment with Ecliptae Herba extract. Results : 1. LPS plays a pivotal roles in inducing to the massive production of pro-inflammatory cytokines such as TNF-$\alpha$, IL-$1{\beta}$ and IL-6 in macrophages. 2. Ecliptae Herba extract reduced the elevated production of cytokines by LPS. 3. Ecliptae Herba extract reduced $PGE_2$ levels in a dose-dependent manner as a consequence of inhibition of COX-2 activity. 4. Ecliptae Herba extract significantly reduced the nuclear translocation of $NF-{\kappa}B$ induced by LPS. 5. In histopathological study, Ecliptae Herba effectively inhibited the increases of hind paw edema, skin thicknesses and inflammatory cell infiltrations induced by carrageenan treatment. Conclusions : These results provide evidences that therapeutic effect of Ecliptae Herba on the acute inflammation is partly due to the reduction of some of inflammatory factors by inhibiting iNOS and COX-2 through the suppression of $NF-{\kappa}B$.

• Development and Reproduction
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• v.21 no.1
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• pp.35-46
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• 2017

The process of spontaneous abortion involves a complex mechanism with various cytokines, growth factors, and hormones during the pregnancy. However, the mechanism underlying spontaneous abortion by pro- and anti-inflammatory cytokines in the serum during the pregnancy is not fully understood. Therefore, the purpose of this study was to examine the relationship between the serum levels of pro- and anti-inflammatory cytokines and spontaneous abortion using the $CBA/j{\times}DBA/2$ mouse model. Serum levels of pro-inflammatory cytokines, such as $IFN-{\gamma}$, $IL-1{\alpha}$ and $TNF-{\alpha}$ were not increased in abortion model mice, but anti-inflammatory cytokines, such as IL-4, IL-13 and IL-1ra were decreased compared to normal pregnant mice. In addition, serum levels of chemokine, such as SDF-1, G-CSF, M-CSF, IL-16, KC and MCP-1 were decreased in abortion model mice compared to normal pregnant mice. However, the expression levels of nesfatin-1/NUCB2 mRNA and protein in the uteri of implantation sites were significantly higher in abortion model mice than normal pregnant mice. These results suggest that uterine nesfatin-1/NUCB2 expression may be down-regulated by inflammatory cytokines and chemokines in the serum of pregnant mice. Moreover, this study suggests the possibility that nesfatin-1/NUCB2 expressed in the implantation sites may be associated with the maintenance of pregnancy.

• Nutrition Research and Practice
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• v.8 no.4
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• pp.352-359
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• 2014

BACKGROUND/OBJECTIVES: In this study, we determined the anti-inflammatory activities and the underlying molecular mechanisms of the methanol extract from Erigeron Canadensis L. (ECM) in LPS-stimulated RAW264.7 macrophage cells. MATERIALS/METHODS: The potential anti-inflammatory properties of ECM were investigated by using RAW264.7 macrophages. We used western blot assays and real time quantitative polymerase chain reaction to detect protein and mRNA expression, respectively. Luciferase assays were performed to determine the transactivity of transcription factors. RESULTS: ECM significantly inhibited inducible nitric oxide synthase (iNOS)-derived NO and cyclooxygenase-2 (COX-2) derived PGE2 production in LPS-stimulated RAW264.7 macrophages. These inhibitory effects of ECM were accompanied by decreases in LPS-induced nuclear translocations and transactivities of $NF{\kappa}B$. Moreover, phosphorylation of mitogen-activated protein kinase (MAPKs) including extracellular signal-related kinase (ERK1/2), p38, and c-jun N-terminal kinase (JNK) was significantly suppressed by ECM in LPS-stimulated RAW264.7 macrophages. Further studies demonstrated that ECM by itself induced heme oxygenase-1 (HO-1) protein expression at the protein levels in dose-dependent manner. However, zinc protoporphyrin (ZnPP), a selective HO-1 inhibitor, abolished the ECM-induced suppression of NO production. CONCLUSIONS: These results suggested that ECM-induced HO-1 expression was partly responsible for the resulting anti-inflammatory effects. These findings suggest that ECM exerts anti-inflammatory actions and help to elucidate the mechanisms underlying the potential therapeutic values of Erigeron Canadensis L.

• Journal of Dental Anesthesia and Pain Medicine
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• v.22 no.5
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• pp.369-376
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• 2022

Background: Nonobstetric surgery is sometimes required during pregnancy, and neck abscess or facial bone fracture surgery cannot be postponed in pregnant women. However, dental surgery can be stressful and can cause inflammation, and the inflammatory response is a well-known major cause of preterm labor. Propofol is an intravenous anesthetic commonly used for general anesthesia and sedation. Studies investigating the effect of propofol on human amnion are rare. The current study investigated the effects of propofol on lipopolysaccharide (LPS)-induced inflammatory responses in human amnion-derived WISH cells. Methods: WISH cells were exposed to LPS for 24 h and co-treated with various concentrations of propofol (0.01-1 ㎍/ml). Cell viability was measured using the MTT assay. Nitric oxide (NO) production was analyzed using a microassay based on the Griess reaction. The protein expression of cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE 2), p38, and phospho-p38 was analyzed using western blotting. Results: Propofol did not affect the viability and NO production of WISH cells. Co-treatment with LPS and propofol reduced COX-2 and PGE₂ protein expression and inhibited p38 phosphorylation in WISH cells. Conclusion: Propofol does not affect the viability of WISH cells and inhibits LPS-induced expression of inflammatory factors. The inhibitory effect of propofol on inflammatory factor expression is likely mediated by the inhibition of p38 activation.