• Advances in Traditional Medicine
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• v.9 no.2
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• pp.115-127
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• 2009

Samsoeum (SSE) is used in traditional oriental medicine for various medicinal purposes. However, the exact mechanism that accounts for the anti-allergy and anti-inflammatory effects of the SSE is still not fully understood. The aim of the present study is to elucidate whether and how SSE modulates the allergic reactions in vivo, and inflammatory reaction in vitro. In this study, we showed that SSE significantly decreased compound 48/80-induced systemic anaphylaxis, ear-swelling response, histamine release from preparation of rat peritoneal mast cells and anti-dinitropheny IgE-induced passive cutaneous reaction. Also, SSE inhibited the expression of inflammatory cytokine and cyclooxygenase-2 in PMA plus A23187-stimulated human mast cells (HMC-1). In addition, we showed that anti-inflammatory mechanism of SSE is through suppression of nuclear factor-${\kappa}B$ activation and $I{\kappa}B-{\alpha}$ phosphorylation/degradation in HMC-1. These results provided new insight into the pharmacological actions of SSE as a potential molecule for therapy of inflammatory allergic diseases.

• YAKHAK HOEJI
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• v.54 no.6
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• pp.500-506
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• 2010

TNF-${\alpha}$ and VCAM-1 play a pivotal role in the pathogenesis of rheumatoid arthritis, and the development of drugs targeting these molecules has extended the therapeutical approaches to rheumatoid arthritis patients. Bispecific antibodies combine the antigen-binding sites of two antibodies within a single molecule and thus they are able to bind to two different epitopes simultaneously. A specific bispecific antibody format termed "Di-diabody" was made for the efficient approach to anti-inflammation. In this study, the DNA vector construct of Di-diabody was built up against two antigens, VCAM-1 and TNF-${\alpha}$. For evaluating this Di-diabody as a bispecific antibody on the efficacy of anti-inflammation, the proteins were analyzed according to each antigen binding affinity and cell based assay related separate molecules. The 7H/Humira Di-diabody produced in this study interacted with its ligands, VCAM-1 and TNF-${\alpha}$, respectively. Also, this antibody exhibited the similar functional activities as compared to 7H-IgG in respect to inhibition of hVCAM-1-induced cell adhesion and Humira-IgG in respect to inhibition of TNF-${\alpha}$ induced cytotoxicity. Further study to elucidate the pharmacological significance of the Di-diabody is warranted using experimental animals.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.2
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• pp.125-133
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• 2022

Carbon monoxide (CO) is a known gaseous bioactive substance found across a wide array of body systems. The administration of low concentrations of CO has been found to exert an anti-inflammatory, anti-apoptotic, anti-hypertensive, and vaso-dilatory effect. To date, however, it has remained unknown whether CO influences atrial natriuretic peptide (ANP) secretion. This study explores the effect of CO on ANP secretion and its associated signaling pathway using isolated beating rat atria. Atrial perfusate was collected for 10 min for use as a control, after which high atrial stretch was induced by increasing the height of the outflow catheter. Carbon monoxide releasing molecule-2 (CORM-2; 10, 50, 100 μM) and hemin (HO-1 inducer; 0.1, 1, 50 μM), but not CORM-3 (10, 50, 100 μM), decreased high stretch-induced ANP secretion. However, zinc porphyrin (HO-1 inhibitor) did not affect ANP secretion. The order of potency for the suppression of ANP secretion was found to be hemin > CORM-2 >> CORM-3. The suppression of ANP secretion by CORM-2 was attenuated by pretreatment with 5-hydroxydecanoic acid, paxilline, and 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one, but not by diltiazem, wortmannin, LY-294002, or NG-nitro-L-arginine methyl ester. Hypoxic conditions attenuated the suppressive effect of CORM-2 on ANP secretion. In sum, these results suggest that CORM-2 suppresses ANP secretion via mitochondrial K_ATP channels and large conductance Ca²⁺-activated K⁺ channels.

• The Korean Journal of Pharmacology
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• v.27 no.2
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• pp.145-153
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• 1991

Human neutrophil cathepsin-G, which has been known as one of the active enzymes causing inflammatory diseases, was purified by two steps procedure involving one size exclusion (Ultorogel AcA54) and one ion exchange (CM-Sephadex) chromatography. Purified HNCGs were cross-reacted with Anti-HNCathepsin-G antibodies which were radised in rabbits and purified by cathepsin-G labeled Sepharose 4B affinity chromatography. HNCGs were effectively inhibited by NSAIDs including phenylbutazone, sulindac, oxyphenbutazone, salicylic acid and salicyluric acid. $IC_{50}_s$ of these drugs for inhibition of Cathepsin G were 0.3-0.8 mM. Other NSAIDs including aspirin showed little or no inhibition effect on the activity of Cathepsin G. These results strongly indicated that NSAIDs which showed inhibition effect on the activity of HNCGs possibly be at least a part of mechanism of action which might be related to direct inhibition of cathepsin G at the tissue destruction sites beside of their known mechanism of action as an anticyclo-oxygenase in treatment of inflammatory diseases. Lipid soluble component of Korean Red Ginseng which was known as an anti-inflammatory agent inhibited HNCGs strongly, but no other fractions did inhibited HNCGs. Antibiotics including novobiosin and rifamycin showed some inhibition effect on HNCGs, i. e.., $IC_{50}$ of these drugs were 2.6 mM and 1.5 mM respectively, and other antibiotics including penicillin G showed no or negligible inhibition effect on the activity of HNCGs. However. tetracyclines inhibited HNCGs very effectively at the concentration of therapeutic range. The inhibition effect of the activity of HNCGs by tetracycline are not related to the N-dimethyl radical on the 4 position of the tetracycline molecule. Furthermore, N-dedimethylated tetracyclines may have beneficial effect for long term treatment of chronic inflammatory diseases without developing any drug resistance to microorganisms.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.55 no.1
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• pp.65-69
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• 2010

This study was carried out to investigate the antioxidative and anti-inflammatory activity of crude anthocyanin compounds extracted from black soybean. The crude anthocyanin compounds were extracted with 80% methanol and concentrated to powder. The most abundant compound isolated from the extract was C3G(cyanidin-3-glucoside). The superoxide dismutase (SOD) assay was conducted to assess the antioxidative activity of the crude extract. SOD, which catalyzes the dismutation of the superoxide anion into hydrogen peroxide and molecular oxygen, is one of the most important antioxidative enzymes. The black soybean anthocyanin extracts inhibited more than 90% of the superoxide radical at a concentration of 0.1% and 100% at a concentration of 0.5%, indicating that this extract displayed excellent antioxidative activity. To assess the anti-inflammatory activity of the extract, a NO(Nitric oxide) production assay in RAW 264.7 cells was performed. NO is an important physiological messenger and effector molecule in many biological systems, including immunological, neuronal and cardiovascular tissues. In this assay, the anthocyanin extracts showed a high anti-inflammatory potential, where the inhibitory potency for NO production was similar to the positive control, particularly for EGCG(epigallocatechin-3-gallate), which is known to have excellent anti-inflammatory activity. Thus, it can be concluded that the anthocyanin extracts from black soybean have distinctive pharmaceutical activities and may be used as an excellent source materials to supplement the health benefits of various food products.

• Journal of Life Science
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• v.33 no.6
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• pp.463-470
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• 2023

Desmarestia tabacoides Okamura is a brown macroalgae that is found worldwide. Although several genera of Desmarestia have been reported as having anti-tumorigenic, anti-melanogenic, and photoprotective properties, the anti-inflammatory activity of D. tabacoides Okamura has not yet been evaluated. In this study, we analyzed the anti-inflammatory mechanisms of D. tabacoides Okamura ethanol extract (DTEE) via the inhibition of nitric oxide (NO) and prostaglandin (PG) E₂ production and the expression of their corresponding enzymes, inducible NO synthase (iNOS), and cyclooxygenase (COX)-2. In addition, their upstream signaling molecules were evaluated by Western blot analysis, such as nuclear factor (NF)-κB, mitogen-activated protein kinase (MAPK), and phosphoinositide-3-kinase (PI3K)/Akt, in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The DTEE treatment significantly inhibited LPS-induced NO and PGE₂ production as well as the expression of their corresponding enzymes, iNOS, and COX-2 without cytotoxicity. The stimulated transcription factor NF-κB and upstream signaling molecules extracellular signal-regulated kinase (ERK), c-Jun NH₂-terminal kinase (JNK), and p38 were attenuated by the DTEE treatment, which was statistically significant, while Akt did not provide any inhibitory effect. Moreover, the DTEE treatment significantly mitigated the LPS-activated adaptor molecules, toll-like receptor 4 (TLR4), and myeloid differentiation primary response 88 (MyD88) in the RAW 264.7 cells. These results suggest that DTEE attenuates TLR4-mediated inflammatory responses by inhibiting NF-κB activation and suppressing MAPK phosphorylation in LPS-stimulated RAW 264.7 cells.

• Journal of Microbiology and Biotechnology
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• v.27 no.11
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• pp.1916-1924
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• 2017

In this study, we synthesized a glycosylated derivative of caffeic acid phenethyl ester (CAPE) using the amylosucrase from Deinococcus geothermalis with sucrose as a substrate and examined its solubility, chemical stability, and anti-inflammatory activity. Nuclear magnetic resonance spectroscopy showed that the resulting glycosylated CAPE (G-CAPE) was the new compound caffeic acid phenethyl ester-4-O-${\alpha}-{\small{D}}$-glucopyranoside. G-CAPE was 770 times more soluble than CAPE and highly stable in Dulbecco's modified Eagle's medium and buffered solutions, as estimated by its half-life. The glycosylation of CAPE did not significantly affect its anti-inflammatory activity, which was assessed by examining lipopolysaccharide-induced nitric oxide production and using a nuclear factor erythroid 2-related factor 2 reporter assay. Furthermore, a cellular uptake experiment using high-performance liquid chromatography analysis of the cell-free extracts of RAW 264.7 cells demonstrated that G-CAPE was gradually converted to CAPE within the cells. These results demonstrate that the glycosylation of CAPE increases its bioavailability by helping to protect this vital molecule from chemical or enzymatic oxidation, indicating that G-CAPE is a promising candidate for prodrug therapy.

• BMB Reports
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• v.30 no.1
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• pp.37-40
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• 1997

Earthworm extracts are known for anti-inflammatory, analgesic. antipyretic, and anticancer effects but can also influence blood circulation. It was previously shown that an earthworm, Lumbricus rubelius. contained a water-extractable anticoagulant which was a heat- and acid-stable molecule with hydrophilic property. In order to uncover the biochemical nature of this molecule, the anticoagulant was processed with various hydrolases such as trypsin, DNase, RNase. and lysozome. When the digested samples were analyzed with an in vitro coagulation test measuring activated partial thromboplastin time (APTT) and agarose gel electrophoresis, the anticoagulant proved to be a relatively homogeneous DNA fragment with relative molecular size around 72 base pairs. Interestingly, the activity was further stimulated with a trypsin digestion. RNA. on the other hand, did not prolong the APTT. It was also demonstrated that the DNA accelerated the antithrombin III (AT-III) inhibition of thrombin from $IC_{50}$ of 0.34 to 0.16 unit determined with S-2238 as a substrate, whereas heparin, a popular anticoagulant. shifted the value to 0.05. Therefore, it is suggested that the DNA could be considered as an alternative antithrombotic agent to heparin, which would exhibits bleeding side effects.

• Journal of Pharmaceutical Investigation
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• v.12 no.2
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• pp.37-44
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• 1982

In order to enhance water solubility, ketoprofen was made as lysine salt, such as acetylsalicylic acid lysine salt, ibuprofen lysine salt and amino acid salt of phenylbutazone. The purpose of this study was to make a comparison between ketoprofen lysine salt in aspects of analgesic, anti-inflammatory, and antipyretic effect. The experimental results were summerized as followings. 1. Ketoprofen lysinate was composed of one molecule of ketoprofen and one molecule of lysine. The product was water soluble and melting point was $92^{\circ}C{\sim}94^{\circ}C$. 2. Ketoprofen lysinate showed about 2 times stronger analgesic effect than that of ketoprofen while no difference in antipyretic effect was observed. 3. $LD_{50}$ of ketoprofen lysinate was higher than that of ketoprofen, suggesting ketoprofen lysinate as safer drug. 4. Blood concentration of ketoprofen lysinate was $156{\mu}g/ml$ while the concentration of ketoprofen was $116{\mu}g/ml$ in 30 min., suggesting long acting as well as high blood concentration.

• IMMUNE NETWORK
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• v.22 no.1
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• pp.9.1-9.23
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• 2022

In the past few decades, biological drugs and small molecule inhibitors targeting inflammatory cytokines, immune cells, and intracellular kinases have become the standard-of-care to treat autoimmune diseases. Inhibition of TNF, IL-6, IL-17, and IL-23 has revolutionized the treatment of autoimmune diseases, such as rheumatoid arthritis, ankylosing spondylitis, and psoriasis. B cell depletion therapy using anti-CD20 mAbs has shown promising results in patients with neuroinflammatory diseases, and inhibition of B cell survival factors is approved for treatment of systemic lupus erythematosus. Targeting co-stimulatory molecules expressed on Ag-presenting cells and T cells is also expected to have therapeutic potential in autoimmune diseases by modulating T cell function. Recently, small molecule kinase inhibitors targeting the JAK family, which is responsible for signal transduction from multiple receptors, have garnered great interest in the field of autoimmune and hematologic diseases. However, there are still unmet medical needs in terms of therapeutic efficacy and safety profiles. Emerging therapies aim to induce immune tolerance without compromising immune function, using advanced molecular engineering techniques.