Jin J.-M.,Seoul National University |
Jin J.-M.,Hong Kong Baptist University |
Lee S.,Seoul National University |
Lee J.,Seoul National University |
And 8 more authors.
Molecular Microbiology | Year: 2010
Apicidin is a cyclic tetrapeptide produced by certain isolates of Fusarium semitectum and has been shown to inhibit Apicomplexan histone deacetylase. An apicidin-producing strain (KCTC16676) of the filamentous fungus was mutated using an Agrobacterium tumefaciens-mediated transformation, resulting in 24 apicidin-deficient mutants. Three of the mutants had a T-DNA insertion in a gene that encodes a non-ribosomal peptide synthetase (NRPS). Results of sequence, expression, and gene deletion analyses defined an apicidin biosynthetic gene cluster, and the NRPS gene was named as apicidin synthetase gene 1 (APS1). A 63 kb region surrounding APS1 was sequenced and analysis revealed the presence of 19 genes. All of the genes including APS1 were individually deleted to determine their roles in apicidin biosynthesis. Chemical analyses of the mutant strains showed that eight genes are required for apicidin production and were used to propose an apicidin biosynthetic pathway. The apicidin analogues apicidin E, apicidin D2 and apicidin B were identified from chemical analysis of the mutants. The cluster gene APS2, a putative transcription factor, was shown to regulate expression of the genes in the cluster and overexpression of APS2 increased apicidin production. This study establishes the apicidin biosynthetic pathway and provides new opportunities to improve the production of apicidin and produce new analogues. © 2010 Blackwell Publishing Ltd.
Yang H.,Seoul National University |
Lee D.Y.,Seoul National University |
Jeon M.,Daewon Pharm. Ltd |
Suh Y.,Seoul National University |
Sung S.H.,Seoul National University
Archives of Pharmacal Research | Year: 2014
Five active compounds, chlorogenic acid, 3,5-di-O-caffeoylquinic acid, 4,5-di-O-caffeoylquinic acid, jaceosidin, and eupatilin, in Artemisia princeps (Compositae) were simultaneously determined by ultra-performance liquid chromatography connected to diode array detector. The morphological resemblance between A. princeps and A. capillaris makes it difficult to properly identify species properly. It occasionally leads to misuse or misapplication in Korean traditional medicine. In the study, the discrimination between A. princeps and A. capillaris was optimally performed by the developed validation method, which resulted in definitely a difference between two species. Also, it was developed the most reliable markers contributing to the discrimination of two species by the multivariate analysis methods, such as a principal component analysis and a partial least squares discrimination analysis. © 2013 The Pharmaceutical Society of Korea.
Ryu J.-H.,Kyung Hee University |
Park J.-S.,Kyung Hee University |
Jo M.-H.,Kyung Hee University |
Kim J.-I.,Kyung Hee University |
And 6 more authors.
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2015
A suitable liquid chromatography tandem mass spectrometry (LC-MS/MS) method is required to determine pelubiprofen and its active metabolite, trans-alcohol (M-D), in human plasma for pharmacokinetic studies of pelubiprofen preparations. After one-step liquid-liquid extraction (LLE) using methyl tert-butyl ether (MTBE), pelubiprofen, M-D, and tolbutamide (the internal standard, IS) were eluted from a Capcellpak C18 ACR column using a gradient mobile phase consisting of 0.1% formic acid in water and acetonitrile at a flow rate 0.35mL/min. The achieved lower limits of quantitation (LLOQ) of pelubiprofen and M-D were both 15ng/mL (S/N>10) and the standard calibration curves for pelubiprofen and M-D were linear (correlation coefficients >0.99) over the studied concentration range (15-2000ng/mL). Intra- and inter-day precisions were within 7.62% for all analytes and the deviation of assay accuracies was within ±13.23%. The developed method was successfully applied to a pharmacokinetic study of pelubiprofen in healthy Korean male volunteers. © 2015 Elsevier B.V.
Anti-inflammatory effect of pelubiprofen, 2-[4-(oxocyclohexylidenemethyl)- phenyl]propionic acid, mediated by dual suppression of COX activity and LPS-induced inflammatory gene expression via NF-κB inactivation
Shin J.-S.,Kyung Hee University |
Baek S.R.,Daewon Pharm. Ltd |
Sohn S.-I.,Daewon Pharm. Ltd |
Cho Y.-W.,Kyung Hee University |
Lee K.-T.,Kyung Hee University
Journal of Cellular Biochemistry | Year: 2011
Pelubiprofen is a non-steroidal anti-inflammatory drugs (NSAIDs) that is related both structurally and pharmacologically to ibuprofen. Anti-inflammatory properties of ibuprofen are due to its ability to both decrease prostaglandin synthesis by inhibiting the activities of cyclooxygenases (COXs) and IκB kinase-β (IKK-β). However, the exact mechanisms that accounts for the anti-inflammatory effects of pelubiprofen are not reported. In this study, we investigated the molecular mechanisms how pelubiprofen modulates the inflammatory mediators in LPS-induced macrophages and carrageenan-induced acute inflammatory rat model. Pelubiprofen potently diminished PGE 2 productions through inhibition of COX enzyme activity (IC 50 values for COX-1 and COX-2 are 10.66 ± 0.99 and 2.88 ± 1.01 μM, respectively), but also reduced the expressions of COX-2, inducible nitric oxide (iNOS), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 at transcriptional level in LPS-induced RAW 264.7 cells. In addition, pelubiprofen attenuated the LPS-induced transcription activity and the DNA binding activity of NF-κB, which was accompanied by a parallel reduction of degradation and phosphorylation of inhibitory kappa B-α (IκB-α) and consequently by decreased nuclear translocation of NF-κB. Furthermore, pelubipofen inhibited the LPS-induced phosphorylation of IKK-β and transforming growth factor-β activated kinase-1 (TAK1). In acute inflammatory rat model, pretreatment with pelubiprofen inhibited carrageenan-induce edema, neutrophil migration, PGE 2 production, and p65, a subunit of NF-κB, nuclear translocation in inflamed paw. Taken together, our data indicated that pelubiprofen is involved in the dual inhibition of COX activity and TAK1-IKK-NF-κB pathway, revealing molecular basis for the anti-inflammatory properties of pelubiprofen. © 2011 Wiley Periodicals, Inc.
Daewon Pharm Co. | Date: 2012-10-23
Antioxidant pills, Chemico-pharmaceutical preparations, Medicines for human purposes, Mineral food-supplements, Nutritional additives for medical purposes, Pharmaceutical preparations , Royal jelly, vitamin preparations, Aloe vera preparations for pharmaceutical purposes, Capsules for pharmaceutical purposes, Lecithin for medical purposes, Magnesia for pharmaceutical purposes , Phosphates for pharmaceutical purposes, Potassium salts for medical purposes, Medicinal roots, Gelatine for medical purposes, Tonics.