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Liu, Qing-Mei,Jung, Hae-Min,Cui, Chang-Hao,Sung, Bong-Hyun,Kim, Jin-Kwang,Kim, Song-Gun,Lee, Sung-Taik,Kim, Sun-Chang,Im, Wan-Taek N.V. Swets en Zeitlinger 2013 Antonie van Leeuwenhoek Vol.103 No.4
<P>A novel α-L-arabinofuranosidase (Abf22-3) that could biotransform ginsenoside Rc into Rd was obtained from the ginsenoside converting Leuconostoc sp. strain 22-3, isolated from the Korean fermented food kimchi. The gene, termed abf22-3, consisting of 1,527 bp and encoding a protein with a predicted molecular mass of 58,486 Da was cloned into the pMAL-c2x (TEV) vector. A BLAST search using the Abf22-3's amino acid sequence revealed significant homology to that of family 51 glycoside hydrolases. The over-expressed recombinant Abf22-3 in Escherichia coli BL21 (DE3) catalyzed the hydrolysis of the arabinofuranoside moiety attached to the C-20 position of ginsenoside Rc under optimal conditions of pH 6.0 and 30 C. This result indicated that Abf22-3 selectively converts ginsenoside Rc into Rd, but did not catalyze the hydrolysis of glucopyranosyl groups from Rc or other ginsenosides such as Rb1 and Rb2. Over-expressed recombinant enzymes were purified by two steps with amylose-affinity and DEAE-cellulose chromatography and then characterized. The kinetic parameters for α-L-arabinofuranosidase showed apparent Km and Vmax values of 0.95 0.02 μM and 1.2 0.1 μmol min(-1) mg of protein(-1) against p-nitrophenyl-α-L-arabinofuranoside, respectively. Using a purified MBP-Abf22-3 (10 μg/ml), 0.1 % of ginsenoside Rc was completely converted to ginsenoside Rd within 20 min.</P>
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Novosphingobium ginsenosidimutans sp. nov., with the Ability to Convert Ginsenoside
( Jin Kwang Kim ),( Dan He ),( Qing Mei Liu ),( Hye Yoon Park ),( Mi Sun Jung ),( Min Ho Yoon ),( Sun Chang Kim ),( Wan Taek Im ) 한국미생물 · 생명공학회 2013 Journal of microbiology and biotechnology Vol.23 No.4
A Gram-negative, strictly aerobic, non-motile, non-sporeforming, and rod-shaped bacterial strain designated FW-6T was isolated from a freshwater sample and its taxonomic position was investigated by using a polyphasic approach. Strain FW-6T grew optimally at 10-42oC and at pH 7.0 on nutrient and R2A agar. Strain FW-6T displayed β- glucosidase activity that was responsible for its ability to transform ginsenoside Rb1 (one of the dominant active components of ginseng) to Rd. On the basis of 16S rRNA gene sequence similarity, strain FW-6T was shown to belong to the family Sphingomonadaceae and was related to Novosphingobium aromaticivorans DSM 12444T (98.1% sequence similarity) and N. subterraneum IFO 16086T (98.0%). The G+C content of the genomic DNA was 64.4%. The major menaquinone was Q-10 and the major fatty acids were summed feature 7 (comprising C18:1 ω9c/ ω12t/ω7c), summed feature 4 (comprising C16:1 ω7c/iso- C15:0 2OH), C16:0, and C14:0 2OH. DNA and chemotaxonomic data supported the affiliation of strain FW-6T to the genus Novosphingobium. Strain FW-6T could be differentiated genotypically and phenotypically from the recognized species of the genus Novosphingobium. The isolate that has ginsenoside converting ability therefore represents a novel species, for which the name Novosphingobium ginsenosidimutans sp. nov. is proposed, with the type strain FW-6T (= KACC 16615T = JCM 18202T).
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Qing Zhao,Xi Jin,Xiao hui Shi,Hui jun Yang,Min Zhang,Junwei Qiao 대한금속·재료학회 2023 METALS AND MATERIALS International Vol.29 No.8
The tribological behavior of TiZrHfNbTa refractory high-entropy alloy (RHEA) sliding against Si3N4ball was investigatedin the air, deionized water and seawater at room temperature as well as under dry condition at high temperature. The resultsshowed that the TiZrHfNbTa RHEA was composed of single BCC phase. The wear rate in air, deionized water and seawaterreached the maximum value of 3.02 × 10−4 mm3/(Nm), 2 × 10−4 mm3/(Nm) and 3.18 × 10−4 mm3/(Nm) at 10 N, respectively. Moreover, the wear rate in deionized water was much lower than that in air, while the wear rate in seawater was close to thatin air. The wear mechanisms were all transitioned from the abrasive wear to adhesive wear with increasing the normal load. At high temperature, the wear rate increased first and then decreased, reached the maximum value of 2.04 × 10–4 mm3/(Nm)at 500 ℃. In addition, oxidation occurred at 400 ℃. The wear mechanism changed from the abrasive wear to oxidation wearat high temperature.
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Choi, Min-Koo,Jin, Qing-Ri,Ahn, Sung-Hoon,Bae, Myung-Ae,Song, Im-Sook Informa Healthcare 2010 Xenobiotica Vol.40 No.12
<OL><LI><P>To assess potential interactions between sitagliptin and metformin, we sought to characterize the <I>in vitro</I> inhibitory potency of sitagliptin on the uptake of MPP<SUP>+</SUP> and metformin, representative substrates for OCTs, and to evaluate the pharmacological pathways that may be affected by the combination of metformin and sitagliptin.</P></LI><LI><P>Among the OATs and OCTs screened, OAT3-mediated salicylate uptake and OCT1- and OCT2-mediated MPP<SUP>+</SUP> uptake were inhibited by sitagliptin. The <I>K</I><SUB>i</SUB> values of sitagliptin for OCT1- and OCT2-mediated metformin uptake were 34.9 and 40.8 μM, respectively.</P></LI><LI><P>As OCT1 is the gate protein for metformin action in the liver, we investigated whether sitagliptin-mediated OCT1 inhibition affected metformin-induced activation of AMPK signalling. Treatment with sitagliptin in MDCK-OCT1 and HepG2 cells resulted in a reduced level of phosphorylated AMPK, with <I>K</I><SUB>i</SUB> values of 38.8 and 43.3 μM, respectively.</P></LI><LI><P>These results suggest that the inhibitory potential of sitagliptin on OCT1 may attenuate the first step of metformin action, that is, the phosphorylation of AMPK. Nevertheless, the likelihood of a drug-drug interaction between sitagliptin and metformin is believed to be remote in usual clinical setting.</P></LI></OL>
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Choi, Min-Koo,Jin, Qing-Ri,Jin, Hyo-Eon,Shim, Chang-Koo,Cho, Doo-Yeoun,Shin, Jae-Gook,Song, Im-Sook WILEY PUBLISHERS 2007 BIOPHARMACEUTICS AND DRUG DISPOSITION Vol.28 No.9
<P>The study sought to investigate the effects of tetraalkylammonium (TAA), inhibitors of the organic cation transporters (OCTs) with different affinities, on the pharmacokinetics of metformin. The inhibitory potentials of TAAs on the uptake of metformin were evaluated by determining IC<SUB>50</SUB> values in MDCK cells over-expressing OCTs and, to assess in vivo drug interactions, metformin and TAAs were coadministered to rats. Uptake of metformin was facilitated by over-expression of hOCT1 and hOCT2 and showed saturable processes, indicating that metformin is a substrate of hOCT1 and hOCT2. The IC<SUB>50</SUB> values of TAAs for hOCT2 were lower than hOCT1 and decreased with increasing alkyl chain length, indicating that the inhibitory potential of TAAs on metformin uptake was greater in hOCT2 than in hOCT1 and increased with increasing alkyl chain length. The plasma concentration of metformin was elevated by the coadministration of tetrapropylammonium (TPrA) and tetrapentylammonium (TPeA), but not by tetramethylammonium (TMA) or tetraethylammonium (TEA). However, the plasma concentrations of TMA, TEA and TPrA were not changed by the coadministration of metformin. In conclusion, in vivo drug interactions between metformin and TAAs were caused only when metformin was coadministered with TAAs showing higher affinities for OCTs. Copyright © 2007 John Wiley & Sons, Ltd.</P>
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Xiao Qing-Hua,Li Wu-Ye,Zhang Jin,Yu Jia-Min,Liu Dong-Yang,Peng Jiang-Nan,Li Mao-Ye,Liu Su 한국응용곤충학회 2024 Journal of Asia-Pacific Entomology Vol.27 No.2
In insects, the transcription factor cap ‘n’ collar isoform C (CncC) plays a critical role in the regulation of multiple genes involved in insecticide detoxification. Knockdown of CncC genes leads to increased susceptibility to different types of insecticides in several insect species. However, the CncC gene has not yet been fully charac terized in the black cutworm Agrotis ipsilon, a notorious insect pest that causes severe damage to field crops. In this study, the CncC gene (designated AiCncC) was identified from A. ipsilon. Exposure to a median lethal con centration (LC 50 ) of chlorantraniliprole (CAP) or phoxim (PHO) strongly increased the expression of AiCncC. Silencing of AiCncC by RNA interference significantly increased the susceptibility of A. ipsilon larvae to both insecticides. Moreover, CncC/Maf binding sites were predicted in the putative promoters of two glutathione S-transferase (GST) genes (AiGSTe1 and AiGSTu1) involved in the detoxification of CAP and PHO. The transcription levels of AiGSTe1 and AiGSTu1 were dramatically decreased by silencing AiCncC. These findings indicate that AiCncC is associated with CAP and PHO susceptibility through the regulation of GST genes.
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Heo, Min-Young,Piao, Zong-Zhu,Kim, Tae-Wan,Cao, Qing-Ri,Kim, Ae-Ra,Lee, Beom-Jin The Pharmaceutical Society of Korea 2005 Archives of Pharmacal Research Vol.28 No.5
Polyethylene glycol (PEG) 6000-based solid dispersions (SDs), by incorporating various pharmaceutical excipients or microemulsion systems, were prepared using a fusion method, t o compare the dissolution rates and bioavailabilities in rats. The amorphous structure of the drug in SDs was also characterized by powder X-ray diffractometry (XRD) and differential scanning calorimetry (DSC). The ketoconazole (KT), as an antifungal agent, was selected as a model drug. The dissolution rate of KT increased when solubilizing excipients were incorporated into the PEG-based SDs. When hydrophilic and lipophilic excipients were combined and incorporated into PEG-based SDs, a remarkable enhancement of the dissolution rate was observed. The PEG-based SDs, incorporating a self microemulsifying drug delivery system (SMEDDS) or microemulsion (ME), were also useful at improving the dissolution rate by forming a microemulsion or dispersible particles within the aqueous medium. However, due to the limited solubilization capacity, these PEG-based SDs showed dissolution rates, below 50% in this study, under sink conditions. The PEG-based SD, with no pharmaceutical excipients incorporated, increased the maximum plasma concentration (C$_{max}$) and area under the plasma concentration curve (AUC$_{0-6h}$) two-fold compared to the drug only. The bioavailability was more pronounced in the cases of solubilizing and microemulsifying PEG-based SDs. The thermograms of the PEG-based SDs showed the characteristic peak of the carrier matrix around 60$^{\circ}C$, without a drug peak, indicating that the drug had changed into an amorphous structure. The diffraction pattern of the pure drug showed the drug to be highly crystalline in nature, as indicated by numerous distinctive peaks. The lack of the numerous distinctive peaks of the drug in the PEG-based SDs demonstrated that a high concentration of the drug molecules was dissolved in the solid-state carrier matrix of the amorphous structure. The utilization of oils, fatty acid and surfactant, or their mixtures, in PEG-based SD could be a useful tool to enhance the dissolution and bioavailability of poorly water-soluble drugs by forming solubilizing and microemulsifying systems when exposed to gastrointestinal fluid.
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Jung, Hae-Min,Liu, Qing-Mei,Kim, Jin-Kwang,Lee, Sung-Taik,Kim, Sun-Chang,Im, Wan-Taek N.V. Swets en Zeitlinger 2013 Antonie van Leeuwenhoek Vol.103 No.4
<P>Biotransformation of ginsenosides was examined using lactic acid bacteria isolated from several kinds of kimchi. A Gram-positive, facultatively anaerobic, non-motile, non-spore-forming, and rod-shaped lactic acid bacterial strain, designated EMML 3041(T), was determined to have ginsenoside-converting activity and its taxonomic position was investigated using a polyphasic approach. Strain EMML 3041(T) displayed β-glucosidase activity that was responsible for its ability to transform ginsenoside Rb1 (one of the dominant active components of ginseng) to F2 via gypenoside XVII, ginsenoside Rb2 to compound Y via compound O, ginsenoside Rc to compound Mc via compound Mc1, and ginsenoside Rd to ginsenoside F2. On the basis of the 16S rRNA gene sequence similarity, strain EMML 3041(T) was shown to belong to the genus Lactobacillus and is closely related to Lactobacillus versmoldensis KU-3(T) (98.3 % sequence similarity). Polyphasic taxonomy study confirmed that the strain EMML 3041(T) represents a novel species, for which the name Lactobacillus ginsenosidimutans sp. nov. is proposed, with EMML 3041(T) (=KACC 14527(T) = JCM 16719(T)) as the type strain.</P>
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