• 약학회지
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• 제41권5호
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• pp.565-570
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• 1997

High levels of extracellular phospholipase $A_2$ (Plase $A_2$) associated with inflammatory process in man and animal models have been extensively reported elsew here. Thus, a logical approach to the treatment of inflammatory diseases should involve the inhibitors of Plase $A_2$. To develop new Plase $A_2$ inhibitors from natural products, two hundred crude drugs were screened using group II PLA$A_2$ inhibitory activity. Among them, methanol extract of 5 medicinal plants such as, Raphani Semen, Moutan cortex radicis, Arecae semen, Caryophylli Cortex and Betulae Cortex inhibited more than 90% of PLase $A_2$ activity at a concentration 2.5${\mu}g/ml$. Then, 10 methanol extracts sample were transferred into organic solvents, PLase $A_2$ inhibitory effects were found mainly in CHCl3 and EtoAc fractions.

• 생명과학회지
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• 제20권4호
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• pp.474-480
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• 2010

흰쥐에서 Interleukin-1 (IL-1)으로 유도된 급성폐손상에서의 group II phospholipase $A_2$ ($PLA_2$) 억제제인 rutin의 효과를 알아보기 위하여 본 연구를 시행하였다. Rutin은 IL-1에 의해 증가한 폐장내의 myeloperoxidase의 활성도를 감소시키지는 못하였으나 폐포세척액 내의 호중구의 수 및 모세혈관의 손상지표로 알려져 있는 폐장 모세혈관에서의 단백질 누출양을 감소시켰다. 동시에 rutin은 IL-1에 의하여 증가한 폐장의 염증조절효소인 $PLA_2$의 활성도를 감소시키고 결과적으로 호중구에서의 산소기의 생성을 감소시켰다. Rutin 뿐만 아니라 manoalide, scalaradial 같은 group II $PLA_2$의 억제제도 호중구의 respiratory burst를 감소시킴을 확인하였다. IL-1에 의하여 증가한 폐포세척액 내에서의 cytokine induced neutrophil chemoattractant의 농도는 rutin에 의해 영향을 받지 않았다. 형태학적으로는 IL-1에 의한 폐장조직에서의 산소기의 형성이 관찰되었고 rutin은 이러한 산소기의 생성을 현저히 감소시켰다. 이러한 결과로 미루어 group II $PLA_2$ 억제제인 rutin은 호중구에서의 활성 산소기의 생성을 효과적으로 억제함으로써 IL-1에 의한 급성폐손상의 감소를 가져 오는 것으로 결론지을 수 있다.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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• pp.195-195
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• 1998

Ginkgetin was previously reported as an inhibitor of group II phospholipase A$_2$. It also inhibited in vitro arachidonate release from the activated macrophages and lymphocyte proliferation. These previous studies suggested an anti-inflammatory nature of ginkgetin, especially on chronic inflammation. In fact, ginkgetin showed potent anti-inflammatory activity against rat adjuvant-induced arthritis, a chronic inflammatory animal model, with comparable analgesic activity. In order to investigate the action mechanisms, tumor necrosis factor and interferone release were studied from human PMMC. It was found that ginkgetin clearly inhibited release of these cytoknes from human PMMC. Ginkgetin was also found to inhibit immunoglobulin M production at 1 - 10 uM. These results may contribute to antiarthritic activity of ginkgetin in vivo.

• The Korean Journal of Physiology and Pharmacology
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• 제4권3호
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• pp.219-226
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• 2000

In order to elucidate the role of platelet activating factor (PAF) in the acute lung injury induced by endotoxin (ETX), activities of phospholipase A2, lyso PAF acetyltransferase and oxidative stress by neutrophilic respiratory burst were probed in the present study. To induce acute lung injury, $100\;{\mu}g$ of E.coli ETX (type 0127; B8) was instilled directly into the tracheae of Sprague-Dawley rats. Five hours after the ETX instillation, induction of acute lung injury was confirmed by lung leak index and protein contents in the bronchoalveolar lavage (BAL) fluid. At the same time, lung phospholipase A2 (PLA2) activity and expression of group I and II secretory type PLA2 were examined. In these acutely injured rats, ketotifen fumarate, known as lyso PAF acetyltransferase inhibitor and mepacrine were administered to examine the role of PAF in the pathogenesis of the acute lung injury. To know the effect of the ETX in the synthesis of the PAF in the lungs, lyso PAF acetyltransferase activity and PAF content in the lungs were measured after treatments of ETX, ketotifen fumarate and mepacrine. In addition, the role of neutrophils causing the oxidative stress after ETX was examined by measuring lung myeloperoxidase (MPO) and enumerating neutrophils in the BAL fluid. To confirm the oxidative stress in the lungs, pulmonary contents of malondialdehyde (MDA) were measured. After instillation of the ETX in the lungs, lung leak index increased dramatically (p＜0.001), whereas mepacrine and ketotifen decreased the lung leak index significantly (p＜0.001). Lung PLA2 activity also increased (p＜0.001) after ETX treatment compared with control, which was reversed by mepacrine and ketotifen (p＜0.001). In the examination of expression of group I and II secretory PLA2, mRNA synthesis of the group II PLA2 was enhanced by ETX treatment, whereas ketotifen and WEB 2086, the PAF receptor antagonist, decreased the expression. The activity of the lysoPAF acetyltransferase increased (p＜0.001) after treatment of ETX, which implies the increased synthesis of PAF by the remodelling of lysoPAF in the lungs. Consequently, the contents of the PAF in the lungs were increased by ETX compared with control (p＜0.001), while mepacrine (p＜0.001) and ketotifen (p＜0.01) decreased the synthesis of the PAF in the lungs of ETX treated rats. The infiltration of the neutrophils was confirmed by measuring and enumerating lung MPO and the neutrophils in the BAL fluid respectively. Compared with control, ETX increased lung MPO and number of neutrophils in BAL significantly (p＜0.001) whereas mepacrine and ketotifen decrerased number of neutrophils (p＜0.001) and MPO (p＜0.05, p＜0.001, respectively). The lung MDA contents were also increased (p＜0.001) by ETX treatment, but treatment with mepacrine (p＜0.001) and ketotifen (p＜0.01) decreased the lung MDA contents. Collectively, we conclude that ETX increases PLA2 activity, and that the subsequently increased production of PAF was ensued by the remodelling of the lyso PAF resulting in tissue injury by means of oxidative stress in the lungs.