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변세은,Jaehwi Lee,Eunji Lee,Song Yi Lee,Eock Kee Hong,Young Eon Kim,Jae Youl Cho 대한약학회 2009 Archives of Pharmacal Research Vol.32 No.11
Mushroom-derived polysaccharides (β-glucans) are considered as a valuable biopharmaceutical principle without displaying side effects. Although Tricholoma matsutake is well-known mushroom in Korea, Japan and China, the immunoregulatory roles of T. matsutake-derived polysaccharides were not fully elucidated yet. In this study, we continued to evaluate the immunomodulatory effect of T. matsutake-derived polysaccharide fraction (TmC-2) using functional activation models of macrophages, monocytes and splenic lymphocytes. TmC-2 treatment strongly increased the production of NO and TNF-α. Phagocytic uptake and ROS generation was also up-regulated by TmC-2. Interestingly, TmC-2 stimulated CD29-mediated cell-cell or cell-finbronectin adhesions in monocytes, while CD43-mediated cell adhesion was down-regulated. Interestingly, the enhancement of proliferation and IFN-γ production was striking observed in TmC-2-treated splenic lymphocytes. The activation seemed to be mediated by up-regulating intracellular signaling cascades such as PI3K/Akt and MAPK (ERK and p38) and by the involvement of surface receptors (dectin-1 and TLR-2). Therefore, our results suggest that this TmC-2 from T. matsutake can be developed as a promising immunostimulatory principle, applicable to people with lowered immunomodulatory potentials.
Inhibition of cytokine expression by a butanol extract from Cordyceps bassiana.
Byeon, Se Eun,Lee, Song Yi,Kim, Ae Ra,Lee, Jaehwi,Sung, Gi Ho,Jang, Hyun-Jae,Kim, Tae-Woong,Park, Hyoung Jin,Lee, Sang-Jin,Hong, Sungyoul,Cho, Jae Youl Govi-Verlag Pharmazeutischer Verlag [etc.] ; Verla 2011 PHARMAZIE Vol.66 No.1
<P>Cordyceps species have been known since long as a multi-utility ethnomedicinal herbal in Korea, China and Japan. It has been reported to exhibit a number of properties such as anti-oxidative, anti-cancer, antiinflammatory, anti-diabetic, and anti-obesity effects. In a previously conducted study, we had demonstrated that the ethanol extract of Cordyceps bassiana was able to suppress the production of interleukin (IL)-12 and interferon (IFN)-gamma in macrophages and T lymphocytes. In this study, we were able to further explore the molecular basis of its inhibitory mechanism using a butanol fraction of this herbal (Cb-BF) preparation. Similarly, this fraction also blocked the expression of cytokines such as IL-12 and tumor necrosis factor (TNF)-alpha as well as the proliferation of splenic lymphocytes and their production of IFN-gamma but not IL-4. Cb-BF suppressed the luciferase activities that are mediated by nuclear factor (NF)-kappaB, activator protein (AP)-1, and signal transducers and activators of transcription (STAT)-1. In agreement with this, these fractions diminished the translocation of the transcription factors into the nucleus. The study also demonstrated that the upstream signaling events for the activation of these factors such as spleen tyrosine kinase (Syk), janus kinase (JAK)-2, and extracellular signal-regulated kinase (ERK) were suppressed. Therefore, these results suggest that the butanol extract of Cordyceps bassiana may contain more than one active component capable of inhibiting the inflammatory signaling cascade and this can be considered as a potential candidate for treatment of diseases that require suppression of immune system.</P>
The distribution and retention of paclitaxel and doxorubicin in multicellular layer cultures
LEE, JOO-HO,NA, KUN,SONG, SOO-CHANG,LEE, JAEHWI,KUH, HYO-JEONG D.A. Spandidos 2012 Oncology reports Vol.27 No.4
<P>Limited distribution of anticancer drugs has been recognized as a significant hurdle to efficacy. We investigated a detailed penetration/distribution profile of paclitaxel-rhodamine (PTX-rd) and doxorubicin (DOX) in multicellular layer (MCL) cultures of human cancer cells as an <I>in vitro</I> model for avascular regions of solid tumors. MCLs were exposed to drugs and fluorescent images of frozen sections were acquired for determination of drug penetration into MCL under various exposure conditions. PTX-rd and DOX showed drastically different profiles of penetration. DOX showed full penetration after 1 h and accumulation over 3 h, whereas PTX-rd showed slow and limited penetration, with accumulation only within the top 20% of layers by 2 h and insignificant penetration even at 72 h. Drug retention in MCL was more dependent on drug concentration, rather than exposure time, i.e., drug distribution increased by 6.3- and 2.5-fold for PTX-rd and DOX, respectively, when exposed to higher concentrations under comparable AUC exposure (1 μM × 24 h vs. 50 μM × 0.5 h). Anti-proliferative activity of PTX and DOX in MCL, as determined by cell cycle analysis, was minimal and may be attributed, at least in part, to their limited distribution in multicellular cultures. Overall, we demonstrated that penetration and retention of PTX and DOX in MCL was not only concentration- and time-dependent, but also schedule-dependent. It is suggested that slow releasing formulations or a slow infusion regimen may not necessarily be desirable, especially for PTX, due to insufficient penetration and accumulation which may result from a low local concentration at the target site.</P>
Soon Wook Hong,Young Wook Choi,Bong Sang Lee,Su Jun Park,Hong Ryeol Jeon,Ki Young Moon,Mean Hyung Kang,Sang Han Park,최성업,Woo Heon Song,Jaehwi Lee 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.1
In order to enhance the dissolution profile and oral bioavailability of megestrol acetate (MA), solid dispersions of MA (MASDs) were formulated with copovidone and crystal sugar as a hydrophilic polymeric carrier and an inert core bead, respectively. Solvent evaporation method and fluidized bed coating technique were employed. MASDs were categorized as crystalline solid dispersion by the characterization of differential scanning calorimetry and X-ray diffraction. The mass-median diameters of MASDs were in a range of 1.4 to 2.6 μm. Based on drug to polymer ratio, MASD (1:1) and (1:2) were considered as optimized formulations, resulting in a smooth-surfaced homogeneously coated layer with enhanced dissolution rate. Dissolution of MASD was gradually increased up to 15 min, after which it reached a plateau. For the initial period, dissolution rates were in the decreasing order of MASD (1:2) ≥ MASD (1:1) > MASD (1:3) > MASD (1:5) > MASD (1:0.5) > MA powder. In the comparative pharmacokinetic study with Megace OS, a reference drug product, MASD (1:1) showed improved bioavailability of over 220% with 2-fold higher C_max and 30% faster T_max. We conclude that MASD (1:1) is a good candidate for the development of oral solid dosage forms.