• YAKHAK HOEJI
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• v.41 no.5
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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.

• Journal of Life Science
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• v.20 no.4
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• pp.474-480
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• 2010

Rutin, a group II phospholipase $A_2$ ($PLA_2$) inhibitor, was tested on interleukin-1 (IL-1) induced acute lung injury (ALI) in male Sprague-Dawley rats. Rutin did not alter the increased lung myeloperoxidase activity by IL-1. However, the number of neutrophils in bronchoalveolar lavage fluid (BALF) and IL-1 induced lung leak were decreased by rutin (p<0.001). Simultaneously, rutin decreased lung $PLA_2$ activity, which was increased by IL-1 (p<0.001). The reduction of neutrophilic respiratory burst by the inhibition of $PLA_2$ was confirmed by group II $PLA_2$ inhibitors such as rutin, manoalide and scalaradial. The increased level of cytokine-induced neutrophilic chemoattractant (CINC) in BALF by IL-1 was not affected by rutin. Ultrastructural changes of ALI and increased generation of free radicals in the lung by IL-1 were found, and rutin ameliorated these pathological findings. Taken together, rutin seems to be effective in decreasing IL-1 induced ALI through inhibition of group II $PLA_2$.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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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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• v.4 no.3
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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.