• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.187-187
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• 1996

세포질에 존재하는 100 kDa Phospholipase $A_2$(cPLA$_2$)는 인지질의 sn-2 위치의 에스테르결합을 가수분해함으로서 Prostaglandin과 Leukotriene등 Eicosanoids 생합성의 전구체인 아라키돈산과 Platelet activating factor(PAF)를 생합성하는 전구체를 동시에 생성시키는 효소로 염증과 세포손상등에 중요한 역할이 기대된다. 본 효소의 활성화 기전을 규명하고자 하는 최근의 활발한 연구에도 불구하고 불명확한 점이 많은 것이 현실이다. 특히 세포를 자극하였을 때 유리되는 아라키돈산의 증가율과 세포를 파괴한 후 조제한 가용성분획에서 측정한 활성의 증가율과는 많은 차이를 나타냈다. 이러한 결과부터 cPLA$_2$ 효소 자체를 활성화시키는 어떤 인자를 가정하였다. 최근, PLA$_2$의 또다른 형태인 14 kDa의 분비성 PLA$_2$의 in vitro 활성을 증가시키는 인자가 동정되어 그 생화학적 특성이 규명되고 있으나 이 인자는 cPLA$_2$의 활성에는 아무런 증가효과를 나타내지 않았다. 본 연구자들은 소의 뇌조직에서 cPLA$_2$의 활성을 증가시키는 인자를 발견하고 그의 생화학적인 특성을 규명하였다. 돼지 비장에서 정제한 cPLA$_2$를 사용하였으며 소의 뇌 조직의 가용성 분획으로부터 본 활성화 인자를 동정하였으며 그 활성분획을 양이온 크로마토그라피로서 Mono S EPLC와 Superose 12 Sepharose gel filtration 크로마토그라피를 이용하여 더욱 분리한 결과 약 70 kDa과 25 kDa에서 각각 용출되었다. 이렇게 부분정제한 활성은 췌장에서 분리한 group I과 흰주의 group I과 흰주의 혈소판에서 분리한 group II PLA$_2$에 대해서는 아무런 증가효과를 나타내지 않는 반면, cPLA$_2$의 활성만을 약 5배 증가시켰다. 본 활성은 cPLA$_2$ 효소량의 증가에 따라 활성의 증가효과가 정차 감소하므로 화학량적인 반응(Stoichiometric reaction)일 것으로 예상되었다.

• Clinical and Experimental Pediatrics
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• v.49 no.6
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• pp.593-601
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• 2006

Allergic rhinitis is a common disease of childhood characterized by nasal, throat, and ocular itching, rhinorrhea, sneezing, nasal congestion. Those affected with allergic rhinitis often suffer from associated inflammatory conditions of the mucosa, such as allergic conjunctivitis, rhinosinusitis, asthma, otitis media with effusion, and other atopic conditions, such as eczema and food allergies. Allergic rhinitis must be diagnosed and treated properly to prevent complications and impaired quality of life. Despite a high prevalence, allergic rhinitis isoften undiagnosed and inadequately treated, especially in the pediatric population. The first step in treatment is environmental control when appropriate. It may be difficult to eliminate all offending allergens effectively to reduce symptoms, so medications are often required. Many different classes of medications are now available, and they have been shown to be effective and safe in a large number of well-designed, clinical trials. Antihistamines are effective in treating immediate symptoms of sneezing, pruritus, watery eyes, and rhinorrhea. Second generation antihistamines are the preferred antihistamines because of their superior side effect profile. Thus, decongestants are commonly used with oral antihistamines. Intranasal corticosteroids are the most effective therapy for allergic rhinitis. Leukotriene modifier may be as effective as antihistamines in treating allergic rhinitis symptoms. Cromolyn sodium is an option for mild disease when used prophylactically, and ipratropium bromide is effective when rhinorrhea is the predominant symptom. When avoidance measures and medications are not effective, specific immunotherapy is an effective alternative. Only immunotherapy results in sustained changes in the immune system. Because of improved understanding of the pathogenesis, new and better therapies may be forthcoming. The effective treatment of allergic rhinitis in children will reduce symptoms and will improve overall health and quality of life, making a happier, healthier child.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.5
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• pp.313-320
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• 2012

In this study, we focused to identify whether eupatilin (5,7-dihydroxy-3',4',6-trimethoxyflavone), an extract from Artemisia argyi folium, prevents $H_2O_2$-induced injury of cultured feline esophageal epithelial cells. Cell viability was measured by the conventional MTT reduction assay. Western blot analysis was performed to investigate the expression of 5-lipoxygenase by $H_2O_2$ treatment in the absence and presence of inhibitors. When cells were exposed to 600 ${\mu}M$ $H_2O_2$ for 24 hours, cell viability was decreased to 40%. However, when cells were pretreated with 25~150 ${\mu}M$ eupatilin for 12 hours, viability was significantly restored in a concentration-dependent manner. $H_2O_2$-treated cells were shown to express 5-lipoxygenase, whereas the cells pretreated with eupatilin exhibited reduction in the expression of 5-lipoxygenase. The $H_2O_2$-induced increase of 5-lipoxygenase expression was prevented by SB202190, SP600125, or NAC. We further demonstrated that the level of leukotriene $B_4$ ($LTB_4$) was also reduced by eupatilin, SB202190, SP600125, NAC, or nordihydroguaiaretic acid (a lipoxygenase inhibitor) pretreatment. $H_2O_2$ induced the activation of p38MAPK and JNK, this activation was inhibited by eupatilin. These results indicate that eupatilin may reduce $H_2O_2$-induced cytotoxicity, and 5-lipoxygenase expression and $LTB_4$ production by controlling the p38 MAPK and JNK signaling pathways through antioxidative action in feline esophageal epithelial cells.

• YAKHAK HOEJI
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• v.56 no.2
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• pp.126-135
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• 2012

Purpose: To develop therapeutic duplication criteria for the drugs used for respiratory diseases. Method: Therapeutic duplication was defined as "more than 2 drug ingredient-usage in which each has the same therapeutic effect and combination therapy does not confer additional therapeutic benefit". Respiratory system drugs approved in Korea were examined for the study. The WHO's Anatomical Therapeutic Chemical Classification System was used for grouping of the corresponding drug ingredients. The principles and recommendations on combination usage or multiple drug regimens were reviewed by using the clinical practice guidelines, textbooks, product labelings, and clinical articles. Clinical expert group consultation was performed and expert opinions were incorporated into the final criteria. Results: Nine hundred sixty two drug products with Korean Food and Drug Administration classification codes of 141, 149, 222, and 229 were evaluated, of which 87 active ingredients were composed. The drug ingredients were classified into 12 groups (antihistamines, oral nasal decongestants, leukotriene receptor antagonists, inhaled anticholinergics, inhaled corticosteroids, oral ${\beta}2$-agonists, long-acting ${\beta}2$-agonists, short-acting ${\beta}2$-agonists, xanthines, antiallergics, mucolytics and cough suppressants). The use of more than 2 drug ingredients including the same group was therapeutic duplication, and thus combination should be recommended not to be used. Conclusion: Twelve drug groups were identified as therapeutic duplication criteria. Combination therapy within each group should not be used otherwise therapeutic benefits outweigh potential risks.

• Korean Journal of Medicinal Crop Science
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• v.15 no.2
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• pp.132-137
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• 2007

Inhibitory effect of Scutellaria baicalensis ethanol extracts (SR) on chemical mediator release and immunoglobulin (Ig) production from Sprague-Dawley rats originated cells as type I allergic reaction was examined. SR showed concentration-dependent inhibition on basal and concanavalin A (ConA)-stimulated Ig production. In the mesenteric lymph node lymphocytes, the inhibitory effect of SR on the IgE production in the presence of Con A was stronger than these on IgA and IgG production. Moreover, tumor necrosis factor-alpha $(TNF-{\alpha})$ production-inhibiting effect of SR in the presence ConA was observed. However, SR did not affect the production of $interferon-{\gamma}$. SR also inhibited histamine release from the peritoneal exudate cells stimulated with a calcium ionophore A23187. In the case of leukotriene B4, SR markedly inhibited it at the concentration of 100 mg/ml. From these results, ethanol extracts obtained from Scutellaria baicalensis may have an anti-allergic effect on the intestinal system of rats.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.4
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• pp.469-474
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• 2012

Fagopyrum esculentum(FE) is an important food crop and medicinal plant that is used to improve diabetes, obesity, hypertension, hypercholesterolemia and constipation in Korea, but the underlying mechanisms involved in its anti-allergic activity are not fully understood. We investigated the effects on the release of inflammatory mediator and proximal signal events in $Fc{\varepsilon}RI$-mediated RBL-2H3 cell activation. FE reduced antigen (DNP-HSA)-induced release of histamine, prostaglandin D2 (PGD2) and cysteinyl Leukotriene (cysLT) in IgE-sensitized RBL-2H3 cells. In addition, it inhibited antigen-induced HDC2 and COX-2 and 5-LO mRNA expression in IgE-sensitized RBL-2H3 cells. FE also suppressed antigen-induced $Fc{\varepsilon}RI{\beta}$ and $Fc{\varepsilon}RI{\gamma}$ subunit mRNA expression in these cells. To identify the mechanisms underpinning the inhibition of release of inflammatory mediators such as histamine and PGD2 and cysLT by FE, we examined the proximal signal events of intracellular FceRI signaling molecules. FE suppressed antigen-induced phosphorylation of Lyn, Syk, LAT, $PLC{\gamma}1$, PI3K, Akt and cPLA2. Collectively, the anti-allergic effects of FE in vitro suggest its possible therapeutic application to inflammatory allergic diseases, in which its inhibition of inflammatory mediator and FceRI-dependent signaling events in mast cells may be hugely beneficial.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.4
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• pp.379-389
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• 2018

A nucleobase adenine is a fundamental component of nucleic acids and adenine nucleotides. Various biological roles of adenine have been discovered. It is not produced from degradation of adenine nucleotides in mammals but produced mainly during polyamine synthesis by dividing cells. Anti-inflammatory roles of adenine have been supported in IgE-mediated allergic reactions, immunological functions of lymphocytes and dextran sodium sulfate-induced colitis. However adenine effects on Toll-like receptor 4 (TLR4)-mediated inflammation by lipopolysaccharide (LPS), a cell wall component of Gram negative bacteria, is not examined. Here we investigated anti-inflammatory roles of adenine in LPS-stimulated immune cells, including a macrophage cell line RAW264.7 and bone marrow derived mast cells (BMMCs) and peritoneal cells in mice. In RAW264.7 cells stimulated with LPS, adenine inhibited production of pro-inflammatory cytokines $TNF-{\alpha}$ and IL-6 and inflammatory lipid mediators, prostaglandin $E_2$ and leukotriene $B_4$. Adenine impeded signaling pathways eliciting production of these inflammatory mediators. It suppressed $I{\kappa}B$ phosphorylation, nuclear translocation of nuclear factor ${\kappa}B$ ($NF-{\kappa}B$), phosphorylation of Akt and mitogen activated protein kinases (MAPKs) JNK and ERK. Although adenine raised cellular AMP which could activate AMP-dependent protein kinase (AMPK), the enzyme activity was not enhanced. In BMMCs, adenine inhibited the LPS-induced production of $TNF-{\alpha}$, IL-6 and IL-13 and also hindered phosphorylation of $NF-{\kappa}B$ and Akt. In peritoneal cavity, adenine suppressed the LPS-induced production of $TNF-{\alpha}$ and IL-6 by peritoneal cells in mice. These results show that adenine attenuates the LPS-induced inflammatory reactions.

• Archives of Plastic Surgery
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• v.42 no.5
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• pp.532-543
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• 2015

Capsular contracture is the most common complication following implant based breast surgery and is one of the most common reasons for reoperation. Therefore, it is important to try and understand why this happens, and what can be done to reduce its incidence. A literature search using the MEDLINE database was conducted including search terms 'capsular contracture breast augmentation', 'capsular contracture pathogenesis', 'capsular contracture incidence', and 'capsular contracture management', which yielded 82 results which met inclusion criteria. Capsular contracture is caused by an excessive fibrotic reaction to a foreign body (the implant) and has an overall incidence of 10.6%. Risk factors that were identified included the use of smooth (vs. textured) implants, a subglandular (vs. submuscular) placement, use of a silicone (vs. saline) filled implant and previous radiotherapy to the breast. The standard management of capsular contracture is surgical via a capsulectomy or capsulotomy. Medical treatment using the off-label leukotriene receptor antagonist Zafirlukast has been reported to reduce severity and help prevent capsular contracture from forming, as has the use of acellular dermal matrices, botox and neopocket formation. However, nearly all therapeutic approaches are associated with a significant rate of recurrence. Capsular contracture is a multifactorial fibrotic process the precise cause of which is still unknown. The incidence of contracture developing is lower with the use of textured implants, submuscular placement and the use of polyurethane coated implants. Symptomatic capsular contracture is usually managed surgically, however recent research has focussed on preventing capsular contracture from occurring, or treating it with autologous fat transfer.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.3
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• pp.438-444
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• 2011

Dojuk-San is known to be effective for treating a urinary diseases and stomatitis. However, its effects on the bone marrow-derived mast cell(BMMC) mediated allergy and inflammation mechanism remain unknown. In this study, the biological effects of Dojuk-San ethanol extract(DJS) were evaluated while focusing on its effects on the allergic mediator in phorbol 12-myristate 13-acetate(PMA) plus calcium ionophore A23187(A23187)-stimulated BMMCs. An investigation was also conducted to determine its effects on the production of several allergic mediators including interleukin-6(IL-6), prostaglandin D2($PGD_2$), leukotrieneC4(LTC4) and ${\beta}$-Hexosaminidase(${\beta}$-Hex). The results revealed that DJS inhibited the PMA plus A23187 induced production of IL-6, PGD2, LTC4 and ${\beta}$-Hex. Taken together, these findings indicate that DJS has the potential using in the treatment of allergy.

• Biomolecules & Therapeutics
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• v.20 no.5
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• pp.477-481
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• 2012

The rhizomes of Acorus gramineus have frequently been used in traditional medicine mainly for sedation as well as enhancing brain function. In this study, the anti-allergic activity of A. gramineus was investigated. The 70% ethanol extract of the rhizomes of A. gramineus was found to inhibit the allergic response against 5-lipoxygenase (5-LOX)-catalyzed leukotriene (LT) production from rat basophilic leukemia (RBL)-1 cells and ${\beta}$-hexosaminidase release from RBL-2H3 cells with $IC_{50}$'s of 48.9 and > $200{\mu}g/ml$, respectively. Among the 9 major constituents isolated, ${\beta}$-asarone, (2R,3R,4S,5S)-2,4-dimethyl-1,3-bis (2',4',5'-trimethoxyphenyl)tetrahydrofuran (AF) and 2,3-dihydro-4,5,7-trimethoxy-1-ethyl-2-methyl-3-(2,4,5-trimethoxyphenyl)indene (AI) strongly inhibited 5-LOX-catalyzed LT production in A23187-treated RBL-1 cells, AI being the most potent ($IC_{50}=6.7{\mu}M$). Against ${\beta}$-hexosaminidase release by antigen-stimulated RBL-2H3 cells, only AI exhibited strong inhibition ($IC_{50}=7.3{\mu}M$) while ${\beta}$-asarone and AF showed 26.0% and 39.9% inhibition at $50{\mu}M$, respectively. In addition, the ethanol extract of A. gramineus showed significant inhibitory action against the hapten-induced delayed hypersensitivity reaction in mice by oral administration at 200 mg/kg. Therefore, it is suggested that A. gramineus possesses anti-allergic activity and the constituents including ${\beta}$-asarone and AI certainly contribute to the anti-allergic activity of the rhizomes of A. gramineus.