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Lee, Kiho,Kwon, Byoung-Mog,Kim, Kangjeon,Ryu, Jekyung,Oh, Soo Jin,Lee, Kye Sook,Kwon, Mu-Gil,Park, Song-Kyu,Kang, Jong Soon,Lee, Chang Woo,Kim, Hwan Mook Taylor Francis 2009 Xenobiotica Vol.39 No.3
<P>The pharmacokinetics and metabolism of 2'-benzoyloxycinnamaldehyde (BCA) was characterized in male Sprague-Dawley rats as part of the preclinical evaluations for developing this compound as an antitumour agent. BCA was not detected in the plasma following either intravenous or oral dose, whereas its putative metabolites 2'-hydroxycinnamaldehyde (HCA) and o-coumaric acid were present at considerable levels. In separate pharmacokinetics studies, HCA exhibited a high systemic clearance and a large volume of distribution, whereas both pharmacokinetic parameters were much lower for o-coumaric acid. The terminal half-life of both metabolites was approximately 2 h. BCA was converted rapidly to HCA in rat serum, liver microsomes and cytosol in vitro; HCA was subsequently converted to o-coumaric acid in a quantitative manner only in the liver cytosol. In addition, the formation of o-coumaric acid was inhibited significantly by menadione, a specific inhibitor for aldehyde oxidase. Taken collectively, the results suggest that the rapid systemic clearance of HCA is likely due mainly to hepatic clearance occurring from aldehyde oxidase-catalysed biotransformation to o- coumaric acid. In conclusion, the present work demonstrates that the anticancer drug candidate BCA is highly likely to work as its active metabolite HCA in the body.</P>
Lee, Soon-Tae,Chu, Kon,Jung, Keun-Hwa,Kim, Se-Jeong,Kim, Dong-Hyun,Kang, Kyung-Mook,Hong, Nan Hyung,Kim, Jin-Hee,Ban, Jae-Joon,Park, Hee-Kwon,Kim, Seung U,Park, Chung-Gyu,Lee, Sang Kun,Kim, Manho,Roh, Macmillan ; Oxford University Press 2008 Brain Vol.131 No.3
<P>Neural stem cell (NSC) transplantation has been investigated as a means to reconstitute the damaged brain after stroke. In this study, however, we investigated the effect on acute cerebral and peripheral inflammation after intracerebral haemorrhage (ICH). NSCs (H1 clone) from fetal human brain were injected intravenously (NSCs-iv, 5 million cells) or intracerebrally (NSCs-ic, 1 million cells) at 2 or 24 h after collagenase-induced ICH in a rat model. Only NSCs-iv-2 h resulted in fewer initial neurologic deteriorations and reduced brain oedema formation, inflammatory infiltrations (OX-42, myeloperoxidase) and apoptosis (activated caspase-3, TUNEL) compared to the vehicle-injected control animals. Rat neurosphere-iv-2 h, but not human fibroblast-iv-2 h, also reduced the brain oedema and the initial neurologic deficits. Human NSCs-iv-2 h also attenuated both cerebral and splenic activations of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and nuclear factor-kappa B (NF-kappaB). However, we observed only a few stem cells in brain sections of the NSCs-iv-2 h group; in the main, they were detected in marginal zone of spleens. To investigate whether NSCs interact with spleen to reduce cerebral inflammation, we performed a splenectomy prior to ICH induction, which eliminated the effect of NSCs-iv-2 h transplantation on brain water content and inflammatory infiltrations. NSCs also inhibited in vitro macrophage activations after lipopolysaccharide stimulation in a cell-to-cell contact dependent manner. In summary, early intravenous NSC injection displayed anti-inflammatory functionality that promoted neuroprotection, mainly by interrupting splenic inflammatory responses after ICH.</P>
Anti-inflammatory Activity of Methanolic Extract Isolated from Immature Fruit of Rhus succedanea
Jong Soon Kang,Chang Woo Lee,Ki Hoon Lee,Mi Hwa Han,Hyunju Lee,Sang-Bae Han,Hyoung-Chin Kim,Kiho Lee,Song-Kyu Park,Hwan Mook Kim 한국실험동물학회 2008 Laboratory Animal Research Vol.24 No.3
In this study, we report the anti-inflammatory activity of methanolic extract isolated from immature fruit of Rhus succedanea (RS). RS dose-dependently inhibited lipopolysaccharide (LPS)-induced production of inflammatory mediators, such as interleukin-1β (IL-1β) and nitric oxide in RAW 264.7 cells, a murine macrophage-like cell line. The mRNA expressions of IL-1β and inducible nitric oxide synthase (iNOS) were also suppressed by RS in LPS-stimulated RAW 264.7 cells. Transient transfection and reporter gene assay demonstrated that LPS-induced NF-κB activity was significantly inhibited by RS in RAW 264.7 cells. Further study demonstrated that topical application of RS suppressed ear swelling in TPA-induced skin inflammation model. Moreover, RS also increased survival rate and time in animal model of sepsis. Collectively, these results suggest that RS exerts an anti-inflammatory effect in vitro and in vivo and this might be mediated, at least in part, by blocking NF-κB activation.