• Biomolecules & Therapeutics
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• v.28 no.4
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• pp.344-353
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• 2020

This study aims to develop new potential therapeutic moracin M prodrugs acting on lung inflammatory disorders. Potential moracin M prodrugs (KW01-KW07) were chemically synthesized to obtain potent orally active derivatives, and their pharmacological activities against lung inflammation were, for the first time, examined in vivo using lipopolysaccharide (LPS)-induced acute lung injury model. In addition, the metabolism of KW02 was also investigated using microsomal stability test and pharmacokinetic study in rats. When orally administered, some of these compounds (30 mg/kg) showed higher inhibitory action against LPS-induced lung inflammation in mice compared to moracin M. Of them, 2-(3,5-bis((dimethylcarbamoyl)oxy)phenyl)benzofuran-6-yl acetate (KW02) showed potent and dose-dependent inhibitory effect on the same animal model of lung inflammation at 1, 3, and 10 mg/kg. This compound at 10 mg/kg also significantly reduced IL-1β concentration in the bronchoalveolar lavage fluid of the inflamed-lungs. KW02 was rapidly metabolized to 5-(6-hydroxybenzofuran-2-yl)-1,3-phenylene bis(dimethylcarbamate) (KW06) and moracin M when it was incubated with rat serum and liver microsome as expected. When KW02 was administered to rats via intravenous or oral route, KW06 was detected in the serum as a metabolite. Thus, it is concluded that KW02 has potent inhibitory action against LPS-induced lung inflammation. It could behave as a potential prodrug of moracin M to effectively treat lung inflammatory disorders.

• Journal of Pharmacopuncture
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• v.14 no.1
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• pp.79-86
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• 2011

Objective : This study was performed to compare anti-inflammation, anti-oxidation and anti-bacterial effects of Cuscutae Semen(CS) extracted with two kinds of solvents, ethanol and distilled water. Methods : Two kinds of CS extractions were prepared 20, 50, 100 ${\mu}l/mg$. The cytotoxicity was measured by MTT assay in Raw 264.7 cell. The anti-inflammation effect was measured by inhibitory efficacy of NO Production in Raw 264.7 cell. The anti-oxidation effect was measured by DPPH Radical scavenging ability in HaCaT cell. The anti-bacterial effect was measured by inhibition zone diameter on Propionibacterium acnes. Results : 1. Two kinds(100 ${\mu}l/mg$) of CS extraction groups had 50% cytotoxicity in Raw 264.7 cell. 2. All of CS extraction groups were not showed significantly inhibitory effect on NO production. 3. All of CS extracted with ethanol only showed dose-dependently significantly scavenging effect of DPPH radicals. 4. Two kinds of CS extractions did not have a inhibitory effect on Propionibactrium acnes. Conclusion : Two kinds(100 ${\mu}l/mg$) of CS extraction groups have 50% cytotoxicity. Two kinds of CS extractions have not the inhibitory effect on NO production and Propionibactrium acnes. CS groups extracted with ethanol only have a significantly scavenging ability of DPPH radicals. This study suggests that CS extracted with ethanol was effective in anti-oxidation.

• Journal of Microbiology and Biotechnology
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• v.21 no.6
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• pp.582-589
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• 2011

Bioconversion of timosaponin A-III (TA-III), one of the major steroidal saponins isolated from the rhizomes of Anemarrhenae asphodeloides Bunge (Liliaceae), was investigated in Saccharomyces cerevisiae. Five bioconversion products, denoted compounds 2-6, were obtained. Biotransformation metabolite 2 was a stereoisomer of TAIII with a specific isotype F-ring and ${\beta}$-ranged $CH_3$-21, which rarely occurs in nature. The structure of 2 was elucidated by extensive spectroscopic analysis (H-H COSY, HSQC, HMBC), as well as by high-resolution mass spectral analysis. The growth inhibitory activity of compounds 1-6 was assayed against four human cancer cell lines, HepG2, H-1299, HT-29, and HCT-116. Compounds 1 and 2 obviously inhibited the growth of the four types of cancer cells with $IC_{50}$ values being less than 19${\mu}M$. A structure-activity relationship is discussed, and the spirostane-ring F in compounds 1 and 2 appears to be the critical bioactive moiety for the cell growth inhibitory property.

• The Journal of Pediatrics of Korean Medicine
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• v.20 no.1
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• pp.241-255
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• 2006

Objective : Allergic Inflammation is related with secretion of Cytokine. This study was performed to examine the effects of Woobangja on anti-allergic inflammation. Method : While macrophage 264.7cells was chosen as a normal group a control group was classified into three groups. One was stimulated with LPS. and another was pretreated with Woobangja for 1 hour. The third was pretreated with gydrocortisone for 1 hour. After the pretreatment, macrophage were incubated with lipopolysaccharide(LPS) 100 ng/ml for 12h and media collected and $TNF-{\alpha}$, IL-6, $IL-1{\beta}$, IL-10 concentration in supernatants were measured each by Enzyme linked immuno-sorbent assay. Woobangja were used $50\;{\mu}g/ml$, $100\;{\mu}g/ml$, $250\;{\mu}g/ml$, $500\;{\mu}g/ml$, 1 mg/ml. Hydrocortisones were used respectively $10^{-8}\;M$,$10^{-7}\;M$,$10^{-6}\;M$,$10^{-5}\;M$,$10^{-4}\;M$. Results : Woobangja showed inhibitory effect on $TNF-{\alpha}$ by LPS-stimulated macrophage 264.7. The inhibitory effect was most significant in 1mg/ml(p<0.01), and has increased according to the number of doses. Woobangja also showed inhibitory effect on IL-10 by LPS-stimulated macrophasg 264.7. The inhibitory effect was most significant in $100\;{\mu}g/ml$, and was not in a dose-dependent manner as Hydrocortisone group. Woobangja and Hydrocortison showed contrary effect on $IL-1{\beta}$ in al five concentration(p<0.01), and at the lowest concentration ($50\;{\mu}g/ml$) the level of $IL-1{\beta}$ was the lowest. On the other hand hydrocortison was observed to have inhibitory effect on $IL-1{\beta}$ in all five concentration(p<0.01). IL-6 was inhibited by hydrocortison in a roughly dose-dependent manner, but was not inhibited by Woobangja. On the contrary Woobangja obviously increased the expression of $IL-1{\beta}$ in all five concentration(p<0.01), but it was not related with concentrations. Conclusion : 1. Woobangja does significantly inhibit the expression of $TNF-{\alpha}$ by LPS-stimulated macrophage 264.7. 2. Woobangja does significantly increse the expression of IL-6 by LPS-stimulated macrophage 264.7. 3. Woobangja does significantly increse the expression of $IL-1{\beta}$ by LPS-stimulated macrophage 264.7. 4. Woobangja does significantly inhibit the expression of IL-10 by LPS-stimulated macrophage 264.7. 5. Woobangja is observer to have anti-allergic inflammatory effect through inhibiting inflammatory cytokine.

• Journal of Microbiology and Biotechnology
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• v.28 no.10
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• pp.1614-1625
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• 2018

Periodontitis, which is a severe inflammatory disease caused by endotoxins secreted from oral pathogens, destructs gingival tissue and alveolar bone. Curcuma xanthorrhiza, commonly called Java turmeric, has been shown to possess anti-bacterial and anti-inflammatory activities. The present study evaluated the inhibitory effect of C. xanthorrhiza supercritical extract (CXS) standardized with xanthorrhizol on lipopolysaccharide (LPS)-induced periodontitis in an animal model. LPS was topically injected into the periodontium of Sprague-Dawley rats to induce periodontitis and CXS (30 and $100mg{\cdot}kg^{-1}{\cdot}day^{-1}$) was orally administered after day 12. Histologically, CXS inhibited the collapse of gingival tissue by preventing cell infiltration. CXS significantly downregulated the expression of matrix metalloproteases (MMPs) and inflammation-related biomarkers, such as nuclear factor-kappa B ($NF-{\kappa}B$) and interleukin-1 beta ($IL-1{\beta}$) in gingival tissue. CXS also improved bone remodeling by downregulating osteoclastic transcription factors, such as nuclear factor of activated T-cells c1 (NFATc1), tartrate-resistant acid phosphatase (TRAP), and cathepsin K. In addition, CXS upregulated osteoblast differentiation-related markers, alkaline phosphate (ALP) and collagen type I alpha (COLA1). Thus, CXS can ameliorate periodontitis by inhibiting inflammation and improving bone remodeling.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.15 no.2
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• pp.33-52
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• 2002

The effects of Arctii fructus extract on allegenic inflammation were investigated using in vivo and in vitro test models. Firstly, the cytotoxicity of Arctii fructus extract was validated using MTT assay. As a result, Arctii fructus extract showed no cytotoxic potential, while SDS, a positive control, revealed strong cytotoxic effect. In LLNA assay, Arctii fructus extract showed no skin allergenicity. Next, the anti-allergic actions of Arctii fructus extract were evaluated using rodent experimental models. The oral, intraperitoneal and intradermal administration of Arctii fructus extract significantly inhibited the compound 48／80-induced vascular permeability documented by Evans blue extravasation. In addition, Arctii fructus extract showed potent inhibitory effect on passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) IgE when orally administered. In an in vitro study, Arctii fructus extract revealed to possess inhibitory potential on the compound 48／80-induced histamine release from rat peritoneal mast cells. Moreover, Arctii fructus extract inhibited the IL-4 and TNF-${\alpha}$ mRNA induction by PMA and A23187 in human leukemia mast cells, HMC-1. Finally, it revealed that Arctii fructus extract significantly suppressed histamin-provoked antigenic inflammation reactions in human prick test. Taken together, these results suggest that anti-allergic action of Arctii fructus extract may be due to the inhibition of histamine release and cytokine gene expression in the mast cells.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.31 no.4
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• pp.22-30
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• 2018

Objectives : The aim of this study is to investigate the relationship between chronic low grade inflammation theory, psoriasis, and herbal medicine. Methods : We reviewed recent studies on the relationship between chronic low-grade inflammation, psoriasis, and herbal medicine through Pubmed. Results : The pathological basis for psoriasis is the action of inflammatory mediators by the activation of the immune response, which can be a cause of various cardiovascular, metabolic and psychological symptoms of psoriasis patients, in addition to skin lesions. The herbal medicines improve these inflammatory conditions and improve local lesions through herbal medicine such as Qingdai, which have a strong inhibitory effect on IL-17,22 production. Conclusions : Herbal medicines used in psoriasis are thought to be effective not only for the improvement of local psoriasis lesions through anti-inflammatory effect but also for the improvement of systemic inflammation associated with chronic low grade inflammation.

• Journal of Pharmacopuncture
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• v.14 no.1
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• pp.71-78
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• 2011

Objective : This study was performed to compare anti-inflammation, anti-oxidation and anti-bacterial effects of Ligustici Rhizoma (LR) extracted with two kinds of solvents, ethanol and distilled water. Methods : It is prepared two kinds of LR extracts 20, 50, 100 ${\mu}l/mg$ by first. MTT assay way to measure cytotoxicity is formed in Raw 264.7 cell. The anti-inflammation effect is measured by ability to inhibit production of NO in Raw 264.7 cell. The anti-oxidation effect was measured by DPPH Radical scavenging ability in HaCaT cell. The anti-bacterial effect was measured by inhibition zone diameter on Propionibacterium acnes. Results : 1. LR (20 ${\mu}l/mg$) extracted with ethanol was showed 80% cytotoxicity, LR (50 ${\mu}l/mg$) extracted with ethanol and LR (20, 50 ${\mu}l/mg$) extracted with water were showed 70% cytotoxicity, LR (100 ${\mu}l/mg$) extracted with ethanol and LR (100 ${\mu}l/mg$) extracted with water were showed 60% cytotoxicity in Raw 264.7 cell. 2. LR (100 ${\mu}l/mg$) extracted with ethanol was showed more significantly inhibitory effect on NO production than the water extraction. 3. Two kinds of LR extraction groups did not show significantly scavenging effect of DPPH radicals. 4. Two kinds of LR extractions did not have a inhibitory effect on Propionibactrium acnes. Conclusion : Two kinds of LR extracts have not cytotoxicity, statistically significant ability to scavenge DPPH radicals and effect to inhibit Propionibactrium acnes. LR extracted with ethanol only have a little effect to inhibit NO production. This study proposes that LR extracted with ethanol is more effective in anti-inflammation.

• The Korea Journal of Herbology
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• v.30 no.1
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• pp.85-93
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• 2015

Objectives : Bilobalide (BIL) is a predominant sesquiterpene trilactone constituent that accounts for a partial portion of the standardized Ginkgonis Folium extract, which has been widely used to treat a variety of neurological disorders involving cerebral ischemia and neurodegeneration. In this study, it was tested whether BIL exhibits anti-inflammatory activities on inflammation response, or not. Methods : To elucidate the molecular mechanisms of BIL on pharmacological and biochemical actions in inflammation, we examined the effect of BIL on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated macrophages. The investigation was focused on how BIL affect on inflammation-related mediators including various signals such as nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), inducible NO synthase(iNOS), cyclooxygenase-2(COX-2), interleukin-6(IL-6), tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), mitogen-activated protein kinases(MAPKs) and nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$) in LPS-stimulated RAW 264.7 cells. Results : We found that BIL inhibited LPS-induced NO, $PGE_2$, IL-6 and $TNF-{\alpha}$ productions as well as the expressions of iNOS and COX-2. Furthermore, BIL suppressed the LPS-induced phosphorylation for MAPK activation. Conclusions : These results suggest that BIL has inhibitory effects on LPS-induced $PGE_2$, NO, IL-6 and $TNF-{\alpha}$ production, as well as the expressions of iNOS and COX-2 in the murine macrophage. It seems that these inhibitory effects occur by blocking the phosphorylation of MAPKs for activation. Then, BIL suppressed the activation of nuclear factor $NF-{\kappa}B$ in nucleus. These observations suggest that BIL has anti-inflammatory effect by inhibiting.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.254.2-254.2
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• 2002

Mast cells play an important role in inflammation by functioning as a source of histamine, tryptase, and proinflammatory cytokines. Lonicera Japonica (Caprifoliaceae. Lc) has been used to treat inflammation. We investigated whether the water extract of Lonicera Japonica(Lc) inhibit production of inflammatory mediators such as tryptase and tumor-necrosis factor (TNF)-${\alpha}$, and phosphorylation of extracellular signal-regulated kinase(ERK) in trypsin-stimulated HMC-1. (omitted)