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Ginsenoside Rb1 increases macrophage phagocytosis through p38 mitogen-activated protein kinase/Akt pathway

  • Xin, Chun;Quan, Hui;Kim, Joung-Min;Hur, Young-Hoe;Shin, Jae-Yun;Bae, Hong-Beom;Choi, Jeong-Il
    • Journal of Ginseng Research
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    • v.43 no.3
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    • pp.394-401
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    • 2019
  • Background: Ginsenoside Rb1, a triterpene saponin, is derived from the Panax ginseng root and has potent antiinflammatory activity. In this study, we determined if Rb1 can increase macrophage phagocytosis and elucidated the underlying mechanisms. Methods: To measure macrophage phagocytosis, mouse peritoneal macrophages or RAW 264.7 cells were cultured with fluorescein isothiocyanate-conjugated Escherichia coli, and the phagocytic index was determined by flow cytometry. Western blot analyses were performed. Results: Ginsenoside Rb1 increased macrophage phagocytosis and phosphorylation of p38 mitogenactivated protein kinase (MAPK), but inhibition of p38 MAPK activity with SB203580 decreased the phagocytic ability of macrophages. Rb1 also increased Akt phosphorylation, which was suppressed by LY294002, a phosphoinositide 3-kinase inhibitor. Rb1-induced Akt phosphorylation was inhibited by SB203580, (5Z)-7-oxozeaenol, and small-interfering RNA (siRNA)-mediated knockdown of $p38{\alpha}$ MAPK in macrophages. However, Rb1-induced p38 MAPK phosphorylation was not blocked by LY294002 or siRNA-mediated knockdown of Akt. The inhibition of Akt activation with siRNA or LY294002 also inhibited the Rb1-induced increase in phagocytosis. Rb1 increased macrophage phagocytosis of IgG-opsonized beads but not unopsonized beads. The phosphorylation of p21 activated kinase 1/2 and actin polymerization induced by IgG-opsonized beads and Rb1 were inhibited by SB203580 and LY294002. Intraperitoneal injection of Rb1 increased phosphorylation of p38 MAPK and Akt and the phagocytosis of bacteria in bronchoalveolar cells. Conclusion: These results suggest that ginsenoside Rb1 enhances the phagocytic capacity of macrophages for bacteria via activation of the p38/Akt pathway. Rb1 may be a useful pharmacological adjuvant for the treatment of bacterial infections in clinically relevant conditions.

Facile synthesis of optical pure fenoxaprop-p-ethyl[ethyl (R)-2-{4-(chloro-1,3-benzoxazol-2-yloxy)phenoxy}propionate] (광학활성 제초제 fenoxaprop-p-ethyl [ethyl (R)-2-{4-(6-chloro-1,3-benzoxazol-2-yloxy)phenoxy}propionate]의 새로운 합성법)

  • Ryu, Sung-Kon;Ko, Young-Kwan;Chang, Hae-Sung;Ryu, Jae-Wook;Woo, Jae-Chun;Koo, Dong-Wan;Kim, Dae-Whang;Chung, Kun-Hoe
    • The Korean Journal of Pesticide Science
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    • v.8 no.1
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    • pp.1-7
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    • 2004
  • Fenoxaprop-p-ethyl[Ethyl (R)-2-{4-(6-chloro-1,3-benzoxazol-2-yloxy)phenoxy}propionate] is well known as a herbicide for its specific activity against the weed grasses. This compound was synthesized by the reaction of 4-(6-chloro-1,3-benzoxazol-2-yloxy)phenol and ethyl (S)-O-(p-toluenesulfonyl)lactate in good yields with high optical pure(optical purity: 99.9% up). In this process Walden inversion occurs, whereby the S-configuration of the propionic acid derivative is converted to the R-configuration of the final product. 4-(6-Chloro-l,3-benzoxazol-2-yloxy)phenol was obtained by 5 step reactions in over-all 70% yields using inexpensive raw materials.

Distribution of Pseudomonas-Derived Cephalosporinase and Metallo-β-Lactamases in Carbapenem-Resistant Pseudomonas aeruginosa Isolates from Korea

  • Cho, Hye Hyun;Kwon, Gye Cheol;Kim, Semi;Koo, Sun Hoe
    • Journal of Microbiology and Biotechnology
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    • v.25 no.7
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    • pp.1154-1162
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    • 2015
  • The emergence of carbapenem resistance among Pseudomonas aeruginosa is an increasing problem in many parts of the world. In particular, metallo-$\beta$-lactamases (MBLs) and AmpC $\beta$lactamases are responsible for high-level resistance to carbapenem and cephalosporin. We studied the diversity and frequency of $\beta$-lactamases and characterized chromosomal AmpC $\beta$lactamase from carbapenem-resistant P. aeruginosa isolates. Sixty-one carbapenem-resistant P. aeruginosa isolates were collected from patients in a tertiary hospital in Daejeon, Korea, from January 2011 to June 2014. Minimum inhibitory concentrations (MICs) of four antimicrobial agents were determined using the agar-dilution method. Polymerase chain reaction and sequencing were used to identify the various $\beta$-lactamase genes, class 1 integrons, and chromosomally encoded and plasmid-mediated ampC genes. In addition, the epidemiological relationship was investigated by multilocus sequence typing. Among 61 carbapenem-resistant P. aeruginosa isolates, 25 isolates (41.0%) were MBL producers. Additionally, 30 isolates producing PDC (Pseudomonas-derived cephalosporinase)-2 were highly resistant to ceftazidime (MIC50 = $256{\mu}g/ml$) and cefepime (MIC50 = $256{\mu}g/ml$). Of all the PDC variants, 25 isolates harboring MBL genes showed high levels of cephalosporin and carbapenem resistance, whereas 36 isolates that did not harbor MBL genes revealed relatively low-level resistance (ceftazidime, p < 0.001; cefepime, p < 0.001; imipenem, p = 0.003; meropenem, p < 0.001). The coexistence of MBLs and AmpC $\beta$-lactamases suggests that these may be important contributing factors for cephalosporin and carbapenem resistance. Therefore, efficient detection and intervention to control drug resistance are necessary to prevent the emergence of P. aeruginosa possessing this combination of $\beta$-lactamases.

Molecular Characterization of Salmonella Genomic Island 1 in Proteus mirabilis Isolates from Chungcheong Province, Korea

  • Sung, Ji Youn;Kim, Semi;Kwon, GyeCheol;Koo, Sun Hoe
    • Journal of Microbiology and Biotechnology
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    • v.27 no.11
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    • pp.2052-2059
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    • 2017
  • The emergence and dissemination of Salmonella genomic island 1 (SGI1) are strongly associated with the occurrence of multidrug-resistant (MDR) enterobacteria in humans and animals. Diverse SGI1s have been reported among Salmonella enterica and Proteus mirabilis in several countries. We aimed to characterize SGI1 in P. mirabilis isolates from humans and chickens in Chungcheong Province, Korea. A total of 44 P. mirabilis isolates were recovered from humans (n = 20) and chickens (n = 24). Antimicrobial susceptibility was determined by disk diffusion assay. To detect and characterize SGI1s, PCR amplification and PCR mapping experiments were performed. Repetitive extragenic palindromic-PCR (REP-PCR) was performed to assess the clonality of the isolates. The four P. mirabilis strains (16.7%) from chicken harbored a SGI1, whereas none of the isolates from clinical specimens contained SGI1. The SGI1s detected in our study were all confirmed as SGI1-PmABB harboring aminoglycoside-resistant genes (aacCA5 and aadA7). In P. mirabilis isolates, the presence of SGI1-PmABB was significantly correlated with high resistance rates of the isolates to antimicrobial agents, such as gentamicin, streptomycin, and spectinomycin. Moreover, the four SGI1-bearing isolates showed the same REP-PCR patterns and that suggested both horizontal and clonal spread of the isolates. This study is the first attempt to determine SGI1s in P. mirabilis isolates in Korea. We confirmed that P. mirabilis isolates carrying SGI1-PmABB were distributed at poultry farms in Korea. The present study emphasizes the need for continuous monitoring of SGI1s to prevent spreading of the MDR genomic islands among P. mirabilis isolates from humans and animals.

Effect of pH on the ATP-sensitive $K^+$ Channel in Aortic Smooth Muscle Cells from Rats

  • Kim, Se-Hoon;Kim, Il-Su;Kim, Hoe-Suk;Jeon, Byeong-Hwa;Chang, Seok-Jong
    • The Korean Journal of Physiology and Pharmacology
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    • v.1 no.5
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    • pp.555-563
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    • 1997
  • The effects of pH on $K^+$ currents were investigated in single smooth muscle cells isolated from the thoracic aorta of Wistar-Kyoto rats. Whole-cell $K^+$ currents were recorded in the conventional configuration of the voltage-clamp technique. Pinacidil (10uM) activated the whole-cell current and the pinacidil-activated current was completely inhibited by glibenclamide (10uM) , an inhibitor of ATP-sensitive $K^+$ channel ($K_{ATP}$ channel). Pinacidil-activated current was reversed at near the $K^+$ equilibrium potential. This current was time- and voltage-independent and reduced by elevating intracellular ATP. Pinacidil-activated current was reduced by lowering the external pH. However, alteration of internal pH has controversial effects on pinacidil-activated current. When the single cell was dialyzed with 0.1 mM ATP, alteration of internal pH had no effect on pinacidil-activated $K^+$ current. In the contrast, when the single cell was dialyzed with 3 mM ATP, pinacidil-activated current was increased by lowering internal pH. Our results suggest that $K^+$ channel activated by pinacidil may be $K_{ATP}$ channel and internal $H^+$ may reduce the inhibitory effect of ATP on $K_{ATP}$ channel.

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Dependence of the Heterojunction Diode Characteristics of ZnO/ZnO/p-Si(111) on the Buffer Layer Thickness (버퍼막 두께에 따른 ZnO/ZnO/p-Si(111) 이종접합 다이오드 특성 평가)

  • Heo, Joo-Hoe;Ryu, Hyuk-Hyun;Lee, Jong-Hoon
    • Korean Journal of Materials Research
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    • v.21 no.1
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    • pp.34-38
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    • 2011
  • In this study, the effects of an annealed buffer layer with different thickness on heterojunction diodes based on the ZnO/ZnO/p-Si(111) systems were reported. The effects of an annealed buffer layer with different thickness on the structural, optical, and electrical properties of zinc oxide (ZnO) films on p-Si(111) were also studied. Before zinc oxide (ZnO) deposition, different thicknesses of ZnO buffer layer, 10 nm, 30 nm, 50 nm and 70 nm, were grown on p-Si(111) substrates using a radio-frequency sputtering system; samples were subsequently annealed at $700^{\circ}C$ for 10 minutes in $N_2$ in a horizontal thermal furnace. Zinc oxide (ZnO) films with a width of 280nm were also deposited using a radio-frequency sputtering system on the annealed ZnO/p-Si (111) substrates at room temperature; samples were subsequently annealed at $700^{\circ}C$ for 30 minutes in $N_2$. In this experiment, the structural and optical properties of ZnO thin films were studied by XRD (X-ray diffraction), and room temperature PL (photoluminescence) measurements, respectively. Current-voltage (I-V) characteristics were measured with a semiconductor parameter analyzer. The thermal tensile stress was found to decrease with increasing buffer layer thickness. Among the ZnO/ZnO/p-Si(111) diodes fabricated in this study, the sample that was formed with the condition of a 50 nm thick ZnO buffer layer showed a strong c-axis preferred orientation and I-V characteristics suitable for a heterojunction diode.

Alteration of 4-Aminopyridine-Sensitive, Voltage-Dependent $K^+-Channel$ in Arterial Smooth Muscle Cells of One-Kidney, One-Clip Goldblatt Hypertensive Rats

  • Kim, Hoe-Suk;Kim, Se-Hoon;Jeon, Byeong-Hwa;Chang, Seok-Jong
    • The Korean Journal of Physiology and Pharmacology
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    • v.4 no.5
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    • pp.385-391
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    • 2000
  • Using the patch-clamp technique, we investigated the alteration of 4-aminopyridine(4-AP)-sensitive, voltage-dependent $K^+$ channel (Kv) in the mesenteric arterial smooth muscle cell (MASMC) of renovascular hypertensive model, one-kidney one-clip Goldblatt hypertensive rat (GBH). To isolate $K_V$ current, internal pipette solution contained 5 mM ATP and 10 mM EGTA. Under these condition, MASMC was depolarized by 4-AP, but charybdotoxin did not affect membrane potential. Membrane potential of hypertensive cell $(-40.3{\pm}3.2\;mV)$ was reduced when compared to that of normotensive cell $(-59.5{\pm}2.8\;mV).$ Outward $K^+$ current of hypertensive cell was significantly reduced when compared to normotensive cell. At 60 mV, the outward currents were $19.10{\pm}1.91$ and $14.06{\pm}1.05$ pA/pF in normotensive cell and hypertensive cell respectively. 4-AP-sensitive $K^+$ current was also smaller in hypertensive cell $(4.28{\pm}0.38\;pA/pF)$ than in normotensive cell $(7.65{\pm}0.52\;pA/pF).$ The values of half activation voltage $(V_{1/2})$ and slope factor (k1) as well as the values of half inactivation voltage $(V_{1/2})$ and slope factor (k1) were virtually similar between GBH and NTR. These results suggest that the decrease of 4-AP-sensitive $K^+$ current contributes to a depolarization of membrane potential, which leads to development of vascular tone in GBH.

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Elimination of Harmful Heavy Metals from Sea Lettuce Enteromorpha sp. with Acid Treatment (산 처리에 의한 파래(Enteromorpha sp.)의 유해 중금속 제거)

  • Mok, Jong Soo;Son, Kwang Tae;Lee, Tae Seek;Kwon, Ji Young;Park, Kunbawui;Kim, Ji Hoe
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.50 no.1
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    • pp.1-7
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    • 2017
  • The elimination of harmful heavy metals (Cd, Cr, and Pb) from sea lettuce Enteromorpha sp. was evaluated in filtered seawater over a pH range of 2.0-4.0 using citric, hydrochloric, and nitric acids. We also evaluated the quality of sea lettuce samples after release of their internal constituents into seawater solutions containing acids. The heavy metals that accumulated in raw sea lettuce after incubation for 3 days in seawater containing Cd, Cr, and Pb were, in descending order, Pb ($120.45{\mu}g/g$), Cr ($86.04{\mu}g/g$), and Cd ($18.35{\mu}g/g$). The rate of elimination of heavy metals from sea lettuce was higher at lower pH for all of the acids used. However, the color of the sea lettuce changed adversely at below pH 2.5. The heavy metals in sea lettuce samples after 10 min in seawater at pH 3.0 containing the three acids were eliminated in the order Pb (42.2-78.0%), Cd (51.8-55.3%), and Cr (14.0-32.8%). The quality of the sea lettuce was not affected when it was incubated for 30 min at pH above 3.0. The maximum elimination of heavy metals from sea lettuce occurred when it was soaked for 10 min in seawater at pH 3.0 containing citric acid.

Econazole Induces p53-Dependent Apoptosis and Decreases Metastasis Ability in Gastric Cancer Cells

  • Choi, Eun Kyoung;Park, Eun Jung;Phan, Tien Thuy;Kim, Hea Dong;Hoe, Kwang-Lae;Kim, Dong-Uk
    • Biomolecules & Therapeutics
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    • v.28 no.4
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    • pp.370-379
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    • 2020
  • Econazole, a potent broad-spectrum antifungal agent and a Ca2+ channel antagonist, induces cytotoxicity in leukemia cells and is used for the treatment of skin infections. However, little is known about its cytotoxic effects on solid tumor cells. Here, we investigated the molecular mechanism underlying econazole-induced toxicity in vitro and evaluated its regulatory effect on the metastasis of gastric cancer cells. Using the gastric cancer cell lines AGS and SNU1 expressing wild-type p53 we demonstrated that econazole could significantly reduce cell viability and colony-forming (tumorigenesis) ability. Econazole induced G0/G1 phase arrest, promoted apoptosis, and effectively blocked proliferation- and survival-related signal transduction pathways in gastric cancer cells. In addition, econazole inhibited the secretion of matrix metalloproteinase- 2 (MMP-2) and MMP-9, which degrade the extracellular matrix and basement membrane. Econazole also effectively inhibited the metastasis of gastric cancer cells, as confirmed from cell invasion and wound healing assays. The protein level of p53 was significantly elevated after econazole treatment of AGS and SNU1 cells. However, apoptosis was blocked in econazole-treated cells exposed to a p53-specific small-interfering RNA to eliminate p53 expression. These results provide evidence that econazole could be repurposed to induce gastric cancer cell death and inhibit cancer invasion.

Two dimensional analysis of axial segregation by convection-diffusion model in batchwise and continuous Czochralski process

  • Wang, Jong-Hoe;Kim, Do-Hyun
    • Proceedings of the Korea Association of Crystal Growth Conference
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    • 1997.10a
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    • pp.117-121
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    • 1997
  • It is shown theoretically that uniform axial dopant concentration distribution can be made throughout the crystal by continuous Czochralski process. Numerical simulation are performed for the transient two-dimensional convection-diffusion model. A typical value of the growth and system parameters for Czochralski growth of p-type, 4 inches silicon crystal was used in the numerical calculations. Using this model with proper model parameter, the axial segregation in batchwise Czochralski growth can be described. It is studied by comparing with the experimental data. With this model parameter, the uniform axial concentration distribution of dopant is predicted in continuous Czochralski process.

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