Identification of anti-osteoclastogenic compounds from <i>Cleistocalyx operculatus</i> flower buds and their effects on RANKL-induced osteoclastogenesis

Tran, Phuong Thao,Ngo, Thi Quynh-Mai,Lee, Suhyun,Kim, Okwha,Tran, Huynh Nguyen Khanh,Hwangbo, Cheol,Min, Byung Sun,Lee, Jeong-Hyung ELSEVIER SCIENCE B.V.; AMSTERDAM 2019 JOURNAL OF FUNCTIONAL FOODS Vol.60 No.-

<P><B>Abstract</B></P> <P> <I>Cleistocalyx operculatus</I> flower buds are used as a main ingredient in various beverages and herbal tea in tropical areas. The present study was conducted to investigate anti-osteoclastogenic effects of ethanol extract of <I>C. operculatus</I> flower buds (ECB) and to identify anti-osteoclastogenic compounds in these buds. ECB significantly inhibited RANKL-induced osteoclast differentiation and decreased RANKL-induced the activation of NFATc1. We isolated nineteen compounds from <I>C. operculatus</I> flower buds and found that eight compounds, including maslinic acid (<B>6</B>) and its two coumaroyl analogs (<B>7</B> and <B>8</B>), significantly inhibited RANKL-induced osteoclast formation. Among these, 3-O-<I>trans</I>-<I>p</I>-coumaroyl maslinic acid (<B>8</B>) showed the most potent inhibitory effect on RANKL-induced osteoclastogenesis via impairment of c-Fos and NF-κB activation, and subsequently, NFATc1 activation. These results suggested that identification of the anti-osteoclastogenic compounds from <I>C. operculatus</I> flower buds may extend our understanding of molecular mechanisms underlying biological activities of <I>C. operculatus</I> flower buds for osteoclast-related diseases.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The anti-osteoclastogenic effect of <I>Cleistocalyx operculatus</I> is demonstrated. </LI> <LI> Ethanol extract of <I>C. operculatus</I> flower buds (ECB) inhibits RANKL-induced osteoclastogenesis. </LI> <LI> Eight compounds are identified as anti-osteoclastogenic compounds from ECB. </LI> <LI> Maslinic acid and its two coumaroyl analogs inhibit RANKL-induced NFATc1 activation. </LI> <LI> The mechanism explains the anti-osteoclastogenic effect of C. operculatus flower buds. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Preliminary Imaging Analysis for Enhanced Intestinal Uptake of Non-soluble Polystyrene Microspheres in the Presence of Oleic Acid using Rat Intestine

Tran, Huyen Thi Thanh,Tran, Phuong Ha Lien,Tran, Thao Truong-Dinh,Lee, Kyung-Ho,Lee, Beom-Jin The Korean Society of Pharmaceutical Sciences and 2009 Journal of Pharmaceutical Investigation Vol.39 No.3

In vitro intestinal uptake of non-soluble polystyrene microspheres (NPMS) was visualized with and without oleic acid using a fluorescence microscopy. Fluorescent polystyrene latex microspheres with 1${\mu}$m larger size were used as models for nonspecifically absorbed nonbiodegradable particulates. The NPMS could not penetrate the enterocytes but a few NPMS could be penetrated via Peyer's patches. When the oleic acid was mixed with NPMS, the transporting efficiency of NPMS through enterocytes as well as Peyer's patches was significantly enhanced. The modification of the intestinal membrane permeability and surface feature of the NPMS in the presence of oleic acid might be a clue to the transport of NSPM although the detailed mechanism is still under investigation.

Biodistribution and <i>in vivo</i> performance of fattigation-platform theranostic nanoparticles

Tran, Thao Truong-Dinh,Tran, Phuong Ha-Lien,Amin, Hardik H.,Lee, Beom-Jin Elsevier 2017 Materials science & engineering. C, Materials for Vol.79 No.-

<P><B>Abstract</B></P> <P>This study was aimed at characterizing superparamagnetic nanoparticles surface-functionalized with gelatin-oleic acid (GOAS-MNPs) and loaded with paclitaxel by assessing the pharmacokinetics and biodistribution of paclitaxel in tissues and the <I>in vivo</I> efficacy of antitumor activity after the administration of the drug. Initially, instrumental analysis was performed to examine the particle size distribution, surface charge, and morphology of the paclitaxel-loaded GOAS-MNPs. Furthermore, we evaluated their magnetic properties and performed T2-weighted magnetic resonance imaging (MRI) on cells. We intravenously administered Taxol® and paclitaxel-loaded GOAS-MNPs and compared the pharmacokinetics, biodistribution, and antitumor efficacies of the two formulations. Determination of the pharmacokinetics and the biodistribution of paclitaxel-loaded NPs showed that this formulation increased the systemic circulation time of paclitaxel and regulated its transport to tissues. The <I>in vivo</I> antitumor efficacy of the paclitaxel-loaded NPs was better than that of Taxol® at the same dose. Furthermore, the paclitaxel-loaded GOAS-MNPs were found to be effective as contrast agents for enhanced MRI in cancer cells. Thus, GOAS-MNPs could be an effective diagnostic system for cancer and for the delivery of paclitaxel with better therapeutic effects and a significant reduction in toxicity.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Improving therapeutic efficacy and lower toxicity </LI> <LI> A significant inhibition of tumor growth </LI> <LI> Could be used as MRI contrast agents </LI> </UL> </P>

Fattigation-platform theranostic nanoparticles for cancer therapy

Tran, Thao Truong-Dinh,Tran, Phuong Ha-Lien,Yoon, Tae-Jong,Lee, Beom-Jin Elsevier 2017 Materials science & engineering. C, Materials for Vol.75 No.-

<P>A new conceptual nanoparticle consisting of a silica-coated iron oxide magnetic core and a fattigation-based biocompatible shell with oleic acid and hydrophilic protein (gelatin). The prepared particle can be a useful theranostics platform material for diagnostic imaging and as a drug delivery system. Oleic acid and gelatin were conjugated on the silica-coated magnetic nanoparticle surface to provide three primary functionalities: 1) enhancing biocompatibility and solubility in aqueous solution and providing the ability to incorporate hydrophobic chemical drugs into the shell for delivery, 2) improving treatment-response magnetic monitoring as a diagnostic agent with low nanotoxicity, and 3) increasing anticancer efficacy owing to the controlled release of the incorporated drug in cells and in an animal model. We prepared magnetic-silica nanoparticles with super paramagnetic properties, which are utilized as a T-2-weighted magnetic resonance imaging agent. After formation of an oleic acid-gelatin shell, the prepared materials exhibited high loading capacity for a hydrophobic anticancer drug (paclitaxel). Our particle platform system exhibited higher therapeutic efficacy and lower toxicological effects in vitro and in an in vivo cancer model than a clinically available chemo-drug (Taxol (R)). Our findings strongly suggest that this nanoparticle system can serve as a platform for cancer therapy by the incorporation of chemical drugs. (C) 2017 Elsevier B.V. All rights reserved.</P>

Modified sprouted rice for modulation of curcumin crystallinity and dissolution enhancement by solid dispersion

Thao T. D. Tran,Thinh D. Luu,Beom‑Jin Lee,Phuong H. L. Tran 한국약제학회 2019 Journal of Pharmaceutical Investigation Vol.49 No.1

Sprouted grains, which is a natural polysaccharide, is the subject of increasing scientific interest due to many benefits for human health. The aim of the present work was to develop sprouted rice (SR) as a safe and useful material for application in dissolution enhancement of anticancer poorly water-soluble drugs such as curcumin by solid dispersions (SDs). SDs were prepared with pure SR and modified sprouted rice (MSR) by the melting method. The dissolution rate, drug crystallinity changes, molecular interactions and wettability were characterized and compared between the formulations. The use of MSR could result in a promising system for improving the dissolution rate of poorly water-soluble drugs. MSR could induce a greater amorphous state and improved wettability of drugs for dissolution enhancement compared to SR. Although both SR and MSR showed hydrogen bonding interaction, insignificant differences between SR and MSR were observed. We found that the crystallinity, interactions and wettability of the drug were significantly affected and modulated by MSR.

Poster Session : Cell Adhesion and Migration ; Phase variation and autolysis mediated by streptococcus pneumoniae chaperone C1pL

( Tran Dang Hien Thao ),( Hye Yoon Jeong ),( Hyog Young Kwon ),( Suhk Neung Pyo ),( Dong Kwon Rhee ) 한국생화학분자생물학회 (구 한국생화학회) 2007 생화학분자생물학회 춘계학술발표논문집 Vol.2007 No.-

Effects of Solvents and Crystallization Conditions on the Polymorphic Behaviors and Dissolution Rates of Valsartan

Thao Truong-Dinh Tran,이범진,Phuong Ha-Lien Tran,박준범 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.7

For the quality evaluation of raw materials, the influence of various types of solvents on the polymorphic crystallization behaviors and dissolution rates of two sources of valsartan (VAL) from China and India was investigated. Samples were prepared by recrystallization from water or organic solvents, such as acetonitrile, acetone and ethanol, using methods with and without heating. Recrystallization behaviors were characterized by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). Scanning electron microscopy (SEM) was also used to observe the morphology of samples. The dissolution rate of recrystallized samples in water was evaluated and compared to the original VAL sample. There were significant differences in morphology, crystal structure and dissolution rate among the samples recrystallized using organic solvents. VAL was transformed into another polymorphic form by the solvents and recrystallization conditions. These physical properties of VAL also differed between the two sources of VAL. Thus, the physicochemical differences of raw materials should be carefully considered in early dosage formulation approaches.

A prenylated flavonoid, 10-oxomornigrol F, exhibits anti-inflammatory effects by activating the Nrf2/heme oxygenase-1 pathway in macrophage cells

Tran, Phi-Long,Tran, Phuong Thao,Tran, Huynh Nguyen Khanh,Lee, Suhyun,Kim, Okwha,Min, Buyng-Sun,Lee, Jeong-Hyung ELSEVIER 2018 INTERNATIONAL IMMUNOPHARMACOLOGY Vol.55 No.-

<P><B>Abstract</B></P> <P>Prenylated flavonoids are a unique class of naturally occurring flavonoids that have various pharmacological activities. In the present study, we investigated the anti-inflammatory effect in murine macrophages of a prenylated flavonoid, 10-oxomornigrol F (OMF), which was isolated from the twigs of <I>Morus alba</I> (Moraceae). OMF inhibited the lipopolysaccharide (LPS)-induced production of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 in RAW264.7 cells, as well as in mouse bone marrow-derived macrophages (BMMs). OMF also rescued LPS-induced septic mortality in ICR mice. LPS-induced expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α and IL-6 was also significantly suppressed by OMF treatment in RAW264.7 cells. Treatment of RAW264.7 cells with OMF induced heme oxygenase (HO)-1 mRNA and protein expression and increased the nuclear translocation of the nuclear factor-E2-related factor 2 (Nrf2) as well as the expression of Nrf2 target genes, such as NAD(P)H:quinone oxidoreductase 1 (NQO1). Treatment of RAW264.7 cells with OMF increased the intracellular level of reactive oxygen species (ROS) and the phosphorylation levels of p38 mitogen-activated protein kinase (MAPK); co-treatment with the antioxidant <I>N</I>-acetyl-cysteine (NAC) blocked this OMF-induced p38 MAPK phosphorylation. Moreover, NAC, or SB203580 (a p38 MAPK inhibitor), blocked the OMF-induced nuclear translocation of Nrf2 and HO-1 expression, suggesting that OMF induces HO-1 expression by activating Nrf2 through the p38 MAPK pathway. Consistent with the notion that the Nrf2/HO-1 pathway has anti-inflammatory properties, inhibiting HO-1 significantly abrogated the anti-inflammatory effects of OMF in LPS-stimulated RAW264.7 cells. Taken together, these findings suggest that OMF exerts its anti-inflammatory effect by activating the Nrf2/HO-1 pathway, and may be a potential Nrf2 activator to prevent or treat inflammatory diseases.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The anti-inflammatory effect of 10-oxomornigrol F, a prenylated flavonoid from <I>Morus alba</I>, is demonstrated. </LI> <LI> The Nrf2/HO-1 pathway is attributable to the anti-inflammatory properties of 10-oxomornigrol F. </LI> <LI> 10-Oxomornigrol F activates the Nrf2/HO pathway via the p38 MAPK pathway. </LI> <LI> The mechanism explains the anti-inflammatory effect of 10-oxomornigrol F. </LI> </UL> </P>

Ganomycin I from <i>Ganoderma lucidum</i> attenuates RANKL-mediated osteoclastogenesis by inhibiting MAPKs and NFATc1

Tran, Phuong Thao,Dat, Nguyen Tien,Dang, Nguyen Hai,Van Cuong, Pham,Lee, Suhyun,Hwangbo, Cheol,Van Minh, Chau,Lee, Jeong-Hyung Elsevier 2019 Phytomedicine Vol.55 No.-

<P><B>ABSTARCT</B></P> <P><B>Background</B></P> <P>Many bone-related diseases such as osteoporosis and rheumatoid arthritis are commonly associated with excessive activity of the osteoclast. Ganomycin I (GMI), a meroterpenoid isolated from Vietnamese mushroom <I>Ganoderma lucidum</I>, possesses a variety of beneficial effects on human health. However, its impact and underlying mechanism on osteoclastogenesis remain unclear. In the present study, we investigated the effect of GMI on RANKL-induced osteoclast formation in mouse BMMs and RAW264.7 cells.</P> <P><B>Methods</B></P> <P>BMMs or RAW264.7 cells were treated with GMI followed by an evaluation of cell viability, RANKL-induced osteoclast differentiation, actin-ring formation, and resorption pits activity. Effects of GMI on RANKL-induced phosphorylation of MAPKs as well as the expression levels of NFATc1 and c-Fos were evaluated by Western blot analysis. Expression levels of osteoclast marker genes were evaluated by Western blot analysis and reverse transcription-qPCR.</P> <P><B>Results</B></P> <P>GMI significantly inhibited RANKL-induced osteoclast differentiation by decreasing the number of osteoclasts, osteoclast actin–ring formation, and bone resorption in a dose-dependent manner without affecting cell viability. At molecular level, GMI inhibited the RANKL-induced phosphorylation of ERK, JNK, and p38 MAPKs, as well as the expression levels of c-Fos and NFATc1, which are known to be crucial transcription factors for osteoclast formation. In addition, GMI decreased expression levels of osteoclastogenesis specific marker genes including c-Src, CtsK, TRAP, MMP-9, OSCAR, and DC-STAMP in RANKL-stimulated BMMs.</P> <P><B>Conclusion</B></P> <P>Our findings suggest that GMI can attenuate osteoclast formation by suppressing RANKL-mediated MAPKs and NFATc1 signaling pathways and the anti-osteoclastogenic activity of GMI may extend our understanding of molecular mechanisms underlying biological activities and pharmacological use of <I>G. lucidum</I> as a traditional anti-osteoporotic medicine.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Heat Shock Protein ClpL Increases Penicillin Resistance by Inducing PBP2X in Streptococcus Pneumoniae

TRAN Thao Dang-Hien,KWON Hyog-Young,KIM Eun-Hye,KIM Ki-Woo,BRILES David E.,PYO Suhkneung,RHEE Dong-Kwon 大韓藥學會 2010 大韓藥學會 總會 및 學術大會 Vol.2010 No.2