• Food Science and Biotechnology
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• v.17 no.4
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• pp.745-750
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• 2008

Anti-inflammatory potential of the enzymatic extract prepared by Kojizyme (ECK), a component of brown seaweeds Ecklonia cava (Alariaceae, Phaeophyta) in vivo was investigated. For the application of mouse ear edema model, 12-O-tetradecanoylphorbol acetate (TPA) was used, a topical inducer of a long-lasting inflammatory response. Our results demonstrated that ECK inhibited ear edema when topically applied to mouse ear skin. In histological evaluation, the inhibition activity of ECK on TPA-induced inflammation is similar to that of dexamethasone, although less strong. In addition, the mRNA expression levels of IL-$1{\beta}$, IFN-$\gamma$, TNF-$\alpha$, and cyclooxygenase-2 (COX2) and the immunoreactivity to inducible nitric oxide synthase (iNOS) and COX2 expressed mainly in inflammatory cells were down-regulated by ECK. These results indicate that ECK has anti-inflammatory effects through the inhibition of Th1 cytokines and 2 inducers of inflammation in TPA-induced ear skin edema.

• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.1.1-1.10
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• 2018

Bone marrow-derived mesenchymal stem cells (BMMSCs) are used extensively for cardiac repair and interact with immune cells in the damaged heart. Macrophages are known to be modulated by stem cells, and we hypothesized that priming macrophages with BMMSCs would enhance their therapeutic efficacy. Rat bone marrow-derived macrophages (BMDMs) were stimulated by lipopolysaccharide (LPS) with or without coculture with rat BMCs. In the LPS-stimulated BMDMs, induction of the inflammatory marker iNOS was attenuated, and the anti-inflammatory marker Arg1 was markedly upregulated by coculture with BMMSCs. Myocardial infarction (MI) was induced in rats. One group was injected with BMMSCs, and a second group was injected with MIX (a mixture of BMMSCs and BMDMs after coculture). The reduction in cardiac fibrosis was greater in the MIX group than in the BMC group. Cardiac function was improved in the BMMSC group and was substantially improved in the MIX group. Angiogenesis was better in the MIX group, and anti-inflammatory macrophages were more abundant in the MIX group than in the BMMSC group. In the BMMSCs, interferon regulatory factor 5 (IRF5) was exclusively induced by coculture with macrophages. IRF5 knockdown in BMMSCs failed to suppress inflammatory marker induction in the macrophages. In this study, we demonstrated the successful application of BMDMs primed with BMMSCs as an adjuvant to cell therapy for cardiac repair.

• Proceedings of the Ginseng society Conference
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• 2002.10a
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• pp.266-276
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• 2002

A red ginseng acidic polysaccharide(RGAP) with immunomodulating antitumor activities was isolated from Korean red ginseng, The molecular weight of RGAP was estimated to be 12-450 kDa by gel filtration chromatography, RGAP was found to increase survival rate and to inhibit of tumor growth significantly in a dose dependent manner in mice transplanted with tumor cells. RGAP significantly promoted nitric oxide(NO) production from peritoneal macrophages bothin vivo and in vitro. Western blot analysis exhibited a newly synthesized inducible nitric oxide synthase(iNOS) protein band in the RGAP treated group. It seems likely that immunomodulating antitumor activities of RGAP are mainly mediated by NO production of macrophage. RGAP was further purified by ultrafiltration and anion exchange chromatography on DEAE-sepharose, followed by gel filtration on Sephacryl S-300 to give an active fraction(GFP) with stronger NO production in murine macrophages. GFP increased survival rate ten times compared to RGAP in male ICR mice transplanted with sarcoma 180 and also showed more potent tumoricidal activities of natural killer cells than RGAP. Sugar $composition(mol\%)$ of GFP was found to be arabinose:rhamnose:xylose:galacturonic acid:mannose:galactose:glucose(10:9:1:25:8:20:27) by GC/MS. The results suggest that clinical trials of RGAP in immunotherapy against cancer are highly feasible.

• The Journal of Korean Obstetrics and Gynecology
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• v.28 no.1
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• pp.113-127
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• 2015

Objectives: This study was performed to analyze the trend of acne-related experimental studies in Korean medicine. Methods: We searched 17 articles related with experimental study of acne, published Korean medical journals from 2005 to 2014. We classified all articles according to the journal and checked on the kind of herbs. All articles were categorized into two types: cell experimental study and animal experimental study. Results: 1. Total 17 papers were searched; 7 articles (41.2%) were published in the Journal of Korean Medical Ophthalmology, Otolaryngology, Dermatology, 4 articles (23.5%) were published in the Journal of Korean Institute of Pharmacopuncture, 3 articles (17.6%) were published in Korean Journal of Oriental Physiology and Pathology, 2 articles (11.8%) were published in Korean Journal of Herbology, and 1 article (5.9%) was published in the Journal of Korean Medicine. 2. Total 17 kind of herbs were used in the studies; 10 articles (58.8%) used single herb, 7 articles (41.2%) used complex herbs. 3. Total 17 articles were categorized 2 types; 16 cell experimental studies (94.1%), 1 animal experimental study (5.9%). 4. Experimental researches were mainly investigated using Raw 264.7 cell line and P. acnes. The levels of NO, iNOS, $TNF-{\alpha}$, PGE, COX-2, $IL-1{\beta}$, IL-6, NF-kB were analyzed to confirm of herbs' antibacterial, anti-inflammatory, antioxidant activity. Conclusions: Searching for natural antibiotics, it is needed to do experimental studies continuously, and also needed to diversify the kind herbs and experimental bacteria.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.23 no.1
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• pp.118-134
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• 2010

Objective: Yang Geouk San Hwa - Tang (YGSHT) has been widely used in Sasang Constitutional Medicine of Korea for treatment of acute inflammatory symptom, such as palatine tonsillitis, polydipsia, headache, papule, pimple however, the mechanism of its anti-inflammatory activity has not been clarified. In this study, therefore, we investigated the mechanism of the inhibitory effect of YGSHT on LPS-induced inflammation. Materials and methods: The effect of YGSHT was analyzed by ELISA, RT-PCR and Western blotting in LPS-stimulated RAW264.7 cells. Results: We found that YGSHT suppressed not only the production of pre-inflammatory cytokines (IL-$1{\beta}$ and TNF-$\alpha$), the generation of nitric oxide (NO) and prostaglandin E (PGE)2, but also the mRNA expression of pre-inflammatory cytokines, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2. Furthermore, YGSHT was shown to inhibit the phosphorylation of ERK1/2 and JNK1/2 and the activation and translocation of NF-kB from cytosol to nuclear in LPS-stimulated RAW264.7 cells. Conclusions: These results suggest that YGSHT exerts an anti-inflammatory effect through the regulation of the ERK1/2 and JNK1/2 pathway and NF-kB pathway, thereby decreasing production of pre-inflammatory cytokines, NO, and PGE2.

• Archives of Pharmacal Research
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• v.27 no.7
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• pp.683-692
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• 2004

Curcumin (diferuloylmethane) is a major naturally-occurring polyphenol of Curcuma species, which is commonly used as a yellow coloring and flavoring agent in foods. Curcumin has shown anti-carcinogenic activity in animal models. Curcumin possesses anti-inflammatory activity and is a potent inhibitor of reactive oxygen-generating enzymes such as lipoxygenase/cyclooxygenase, xanthine dehydrogenase/oxidase and inducible nitric oxide synthase; and an effective inducer of heme oxygenase-1. Curcumin is also a potent inhibitor of protein kinase C(PKC), EGF(Epidermal growth factor)-receptor tyrosine kinase and LĸB kinase. Subsequently, curcumin inhibits the activation of NF(nucleor factor)KB and the expressions of oncogenes including c-jun, c-fos, c-myc, NIK, MAPKs, ERK, ELK, PI3K, Akt, CDKs and iNOS. It is proposed that curcumin may suppress tumor promotion through blocking signal transduction path-ways in the target cells. The oxidant tumor promoter TPA activates PKC by reacting with zinc thiolates present within the regulatory domain, while the oxidized form of cancer chemopreventive agent such as curcumin can inactivate PKC by oxidizing the vicinal thiols present within the catalytic domain. Recent studies indicated that proteasome-mediated degradation of cell proteins playa pivotal role in the regulation of several basic cellular processes including differentiation, proliferation, cell cycling, and apoptosis. It has been demonstrated that curcumin-induced apoptosis is mediated through the impairment of ubiquitin-proteasome pathway. Curcumin was first biotransformed to dihydrocurcumin and tetrahydrocurcumin and that these compounds subsequently were converted to monoglucuronide conjugates. These results suggest that curcumin-glucuronide, dihydrocurcumin-glucuronide, tetrahydrocurcumin-glucuronide and tetrahydrocurcumin are the major metabolites of curcumin in mice, rats and humans.

• Journal of Chitin and Chitosan
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• v.22 no.3
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• pp.185-193
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• 2017

Red tide Heterosigma akashiwo (H. akashiwo), a microscopic alga of the class Raphidophyceae, causes extensive damage to all marine ecosystems. It is essential to reduce the damage to marine ecosystems for them to be used as a resource. In this study, we used organic solvent fractionation to obtain an ethyl acetate-methanol extract from H. akashiwo (HAEM80) and then evaluated its anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and a zebrafish model. HAME80 markedly inhibited the production of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$). It also down-regulated the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and decreased the secretion of interleukin-$1{\beta}$ ($IL-1{\beta}$) in LPS-stimulated RAW 264.7 cells. HAME80 reduced yolk edema and improved the survival rate of LPS-stimulated zebrafish embryos; in addition, the extract significantly reduced the production of ROS and NO and attenuated cell death in this model. Gas chromatography-mass spectrometry (GC-MS) of the extract was used to confirm the identity of peaks 1-20. Taken together, our data suggest that H. akashiwo is a beneficial anti-inflammatory agent.

• Journal of Ginseng Research
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• v.45 no.5
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• pp.575-582
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• 2021

Background: In ginseng, there exists a glycolipoprotein complex with a special form of lipid LPAs called Gintonin. The purpose of this study is to show that Gintonin has a therapeutic effect on rheumatoid arthritis through LPA2 receptors. Methods: Fibroblast-like synoviocytes (FLS) were treated with Gintonin and stimulated with interleukin (IL)-1β. 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, phosphorylation of mitogen-activated protein kinase (MAPK) pathways, and translocation of nuclear factor kappa B (NF-κB)/p65 into the nucleus through western blot. Next, after treatment with LPAR2 antagonist, western blot analysis was performed to measure inflammatory mediator expression levels, and NF-κB signaling pathway. Carrageenan/kaolin-induced arthritis rat model was used. Rats were orally administered with Gintonin (25, 50, and 100 mg/kg) every day for 6 days. The knee joint thickness, squeaking score, and weight distribution ratio (WDR) were measured as the behavioral parameters. After sacrifice, H&E staining was performed for histological analysis. Results: Gintonin significantly inhibited the expression of iNOS, TNF-α, IL-6 and COX-2. Gintonin prevented NF-κB/p65 from moving into the nucleus through the JNK and ERK MAPK phosphorylation in FLS cells. However, pretreatment with an LPA2 antagonist significantly reversed these effects of Gintonin. In the arthritis rat model, Gintonin suppressed all parameters that were measured. Conclusion: This study suggests that LPA2 receptor plays a key role in mediating the anti-arthritic effects of Gintonin by modulating inflammatory mediators, the MAPK and NF-κB signaling pathways.

• Journal of Veterinary Clinics
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• v.36 no.2
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• pp.102-105
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• 2019

Nitrotyrosine was found to be dependent on the severity of myxomatous mitral valve disease (MMVD). However, a correlation of serum nitrotyrosine concentration in dogs with MMVD and the progression of the disease has not been investigated. This study compared changes in serum nitrotyrosine concentration with the progression of MMVD. Nine client-owned dogs were recruited for the study. Dogs were classified by measuring the amount of regurgitation using echocardiography into mild, moderate, or severe MMVD groups. Serum nitrotyrosine concentration was measured by an enzyme-linked immunosorbent assay test. Serum nitrotyrosine concentration was significantly higher at 180 days than at 0 day (P < 0.05). However, serum nitrotyrosine concentration at 360 days was lower than that at 180 days (P < 0.05). Serum nitrotyrosine concentration at 540 days was lower than at 180 days (P < 0.05). There was no correlation between serum nitrotyrosine and left atrial to aortic root diameter ratio (LA/Ao ratio) (n = 33, $R^2=0.003$, P = 0.759). Also, there was no correlation between serum nitrotyrosine and vertebral heart score (VHS) (n = 33, $R^2=0.026$, P = 0.368) and left ventricular end-diastolic diameter, normalized for body weight by the formula (LVEDDN) (n = 33, $R^2=0.053$, P = 0.196). The results of the study suggest that the progression of MMVD is correlated with changes in serum nitrotyrosine concentration, which shows potential for use as a cardiac biomarker which can be used to analyze the progression of disease in MMVD.

• Korean Journal of Pharmacognosy
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• v.49 no.4
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• pp.305-311
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• 2018

Osteoarthritis (OA) is the most common form of joint disease, characterized by articular cartilage, osteonecrosis, and osteochondral bone erosion. It is an early, progressive disease that combines joint stiffness and joint pain and reduces cartilage function and condition. Interleukin-1 beta ($IL-1{\beta}$) is thought to be important to the pathogenesis of OA and significantly increases the expression of matrix metalloproteinases (MMPs), which play an important role in cartilage degradation in OA. Sparassis crispa (Wulf.) is an edible / medicinal mushroom that has been reported to variety of biological activities. In this study, investigated the Anti-inflammatory effect of Sparassis crispa (Wulf.) ethanol extract (SCE) on $IL-1{\beta}$ stimulated SW1353 chondrocytes. SCE decreased the expression and activity of MMPs by $IL-1{\beta}$ and decreased the levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) associated with the inhibition of prostaglandin E2($PGE_2$) in $IL-1{\beta}$ stimulated SW-1353 chondrocytes. In addition, SCE inhibits the expression of MAPK (mitogen-activated protein kinase) and $NF-{\kappa}B$ (nuclear factor-kappa B) signaling in $IL-1{\beta}$ stimulated SW-1353 cells, and SCE inhibits the production of reactive oxygen species (ROS) through heme oxygenase-1 (HO-1) expression. Thus, it is suggested that SCE has a potential as an anti-inflammatory agent in osteoarthritis treatments.