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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Biomolecules & Therapeutics
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Journal DOI :
The Korean Society of Applied Pharmacology
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Volume & Issues
Volume 18, Issue 4 - Oct 2010
Volume 18, Issue 3 - Jul 2010
Volume 18, Issue 2 - Apr 2010
Volume 18, Issue 1 - Jan 2010
Selecting the target year
Therapeutic Application of Nitric Oxide in Human Diseases
NamKoong, Seung ; Kim, Young-Myeong ;
Biomolecules & Therapeutics, volume 18, issue 4, 2010, Pages 351~362
DOI : 10.4062/biomolther.2010.18.4.351
Nitric oxide (NO), synthesized from L-arginine by three isoforms of NO synthase (NOS), is a gaseous signaling molecule with an astonishingly wide range of biological and pathophysiological activities, including vasorelaxation, angiogenesis, anti-inflammation, and anti-apoptosis in mammalian cells. Recent studies have shown that NO donors and inhaled NO convert to biologically active NO under biological conditions and act as a signaling molecule in pathophysiological conditions. This review will discuss the roles of NO and its potential therapeutic implication in various human diseases, such as tumor, vascular regeneration, hypertension, wound healing, and ischemia-reperfusion injury.
Roles of Leptin in Cancer Progression
Kang, Yu-Jin ; Moon, A-Ree ;
Biomolecules & Therapeutics, volume 18, issue 4, 2010, Pages 363~374
DOI : 10.4062/biomolther.2010.18.4.363
Growing evidence suggests a prominent role for leptin in human cancer progression. The intricate pattern of leptin cross-talk with other associated signaling pathways is a critical area of research that will ultimately contribute to comprehending the role of leptin in cancer progression. This review summarizes a portion of the current understanding of leptin signaling, with a critical focus on its contribution to tumor cell invasion and metastasis. Five topics are addressed in this review: (1) Leptin receptor, (2) Leptin signaling, (3) Leptin and cancer, and (4) Leptin and tumor invasion. Due to the complex cellular effects of leptin, a more precise understanding of leptin signaling pathways must still be elucidated. Leptin is clearly a major factor for stimulating tumor progression through a complex spectrum of interplay and cross-talk among various signaling molecules. An understanding of the role of leptin in invasion and metastasis will provide valuable information for establishing strategies to modulate leptin signaling, which should be a high priority for the development of anti-cancer therapeutics.
Targeting Multidrug Resistance with Small Molecules for Cancer Therapy
Xia, Yan ; Lee, Kyeong ;
Biomolecules & Therapeutics, volume 18, issue 4, 2010, Pages 375~385
DOI : 10.4062/biomolther.2010.18.4.375
Conventional cancer chemotherapy is seriously limited by tumor cells exhibiting multidrug resistance (MDR), which is caused by changes in the levels or activity of membrane transporters that mediate energy-dependent drug efflux and of proteins that affect drug metabolism and/or drug action. Cancer scientists and oncologists have worked together for some time to understand anticancer drug resistance and develop pharmacological strategies to overcome such resistance. Much focus has been on the reversal of the MDR phenotype by inhibition of ATP-binding cassette (ABC) drug transporters. ABC transporters are a family of transporter proteins that mediate drug resistance and low drug bioavailability by pumping various drugs out of cells at the expense of ATP hydrolysis. Many inhibitors of MDR transporters have been identified, and though some are currently undergoing clinical trials, none are in clinical use. Herein, we briefly review the status of MDR in human cancer, explore the pathways of MDR in chemotherapy, and outline recent advances in the design and development of MDR modulators.
A Comparison of ROCK Inhibitors on Human Bone Marrow-Derived Mesenchymal Stem Cell Differentiation into Neuron-Like Cells
Lee, Hyun-Sun ; Kim, Kwang-Sei ; O, Eun-Ju ; Joe, Young-Ae ;
Biomolecules & Therapeutics, volume 18, issue 4, 2010, Pages 386~395
DOI : 10.4062/biomolther.2010.18.4.386
Bone marrow-derived mesenchymal stem cells (BM-MSC) are a multipotent cell population that can differentiate into neuron-like cells. Previously it has been reported that murine BM-MSC can differentiate into neuron-like cells by co-treatment with a Rho-associated kinase (ROCK) inhibitor -Y27632 and
. In this study, we compared several ROCK inhibitors for the ability to induce human BM-MSCs to differentiate into neuron-like cells in the presence of
. Y27632 with high specificity for ROCK at 1-30
was best at inducing neuronal differentiation of MSCs. Compared to HA1077 and H1152, which also effectively induced morphological change into neuron-like cells, Y27632 showed less toxicity even at 100
, and resulted in longer multiple branching processes at a wide range of concentrations at 6 h and 72 h post-induction. H89, however, which has less specificity by inhibition of protein kinase A, S6 kinase 1 and MSK1 with similar or greater potency, was less effective at inducing neuronal differentiation of MSCs. Simvastatin, which can inhibit Rho, Ras, and Rac by blocking the synthesis of isoprenoid intermediates, showed little activity for inducing morphological changes of MSCs into neuron-like cells. Accordingly, the expression patterns for neuronal cell markers,including
-tubulin III, neuron-specific enolase, neurofilament, and microtubule-associated protein, were consistent with the pattern of the morphological changes. The data suggest that the ROCK inhibitors with higher specificity are more effective at inducing neuronal differentiation of MSCs.
Effects of Baicalin, Baicalein and Schizandrin on Airway Mucin Production Induced by Epidermal Growth Factor and Phorbol Ester
Lee, Hyun-Jae ; Lee, Su-Yel ; Kim, Young-Sik ; Jeon, Byeong-Kyou ; Lee, Jae-Woo ; Bae, Heung-Seog ; Lee, Choong-Jae ;
Biomolecules & Therapeutics, volume 18, issue 4, 2010, Pages 396~401
DOI : 10.4062/biomolther.2010.18.4.396
We conducted this study to investigate whether baicalin, baicalein or schizandrin significantly affect MUC5AC mucin production induced by epidermal growth factor (EGF) or phorbol ester (PMA) in human airway epithelial cells. Confluent NCI-H292 cells were pretreated with varying concentrations of baicalin, baicalein or schizandrin for 30 min and then stimulated with EGF or PMA for 24 h, respectively. MUC5AC mucin protein production was measured by ELISA. The results were as follows: (1) Baicalin was found to inhibit the production of MUC5AC mucin protein induced by both EGF and PMA. (2) Baicalein, the aglycone of baicalin, also inhibited MUC5AC mucin production. (3) Schizandrin, derived from Schizandrae Fructus, inhibited MUC5AC mucin production by the same inducers. These results suggest that baicalin, baicalein and schizandrin can regulate the production of mucin protein by directly acting on human airway epithelial cells.
Suppression of Prostaglandin E
-Mediated Cell Proliferation and Signal Transduction by Resveratrol in Human Colon Cancer Cells
Song, Su-Hyun ; Min, Hye-Young ; Lee, Sang-Kook ;
Biomolecules & Therapeutics, volume 18, issue 4, 2010, Pages 402~410
DOI : 10.4062/biomolther.2010.18.4.402
Although the overproduction of prostaglandin
) in intestinal epithelial cells has been considered to be highly correlated with the colorectal carcinogenesis, the precise mechanism of action remains poorly elucidated. Accumulating evidence suggests that the PGE receptor (EP)-mediated signal transduction pathway might play an important role in this process. In the present study, we investigated the mechanism of action underlying
-mediated cell proliferation and the effect of resveratrol on the proliferation of human colon cancer cells in terms of the modulating
-mediated signaling pathway.
stimulated the proliferation of several human colon cancer cells and activated growth-stimulatory signal transduction, including Akt and ERK.
also increased the phosphorylation of GSK-
, the translocation of
-catenin into the nucleus, and the expressions of c-myc and cyclin D1. Resveratrol, a cancer chemopreventive phytochemical, however, inhibited
-induced growth stimulation and also suppressed
-mediated signal transduction, as well as
-catenin/T cell factor-mediated transcription in human colon cancer cells. These findings present an additional mechanism through which resveratrol affects the regulation of human colon cancer cell growth.
Effect of Korean Mistletoe Lectin on Gene Expression Profile in Human T Lymphocytes: A Microarray Study
Lyu, Su-Yun ; Park, Won-Bong ;
Biomolecules & Therapeutics, volume 18, issue 4, 2010, Pages 411~419
DOI : 10.4062/biomolther.2010.18.4.411
Korean mistletoe has a variety of biological effects, such as immunoadjuvant activities. This study investigates the effects of Korean mistletoe lectin (Viscum album L. var. coloratum agglutinin, VCA) on human T lymphocytes to determine whether VCA acts as an immunomodulator. Purified human T-lymphocytes were cultured with VCA and RNA from each point was analyzed using Affymetrix human genome chips containing 22,500 probe sets which represents more than 18,000 transcripts derived from 14,500 human genes. As a result, there was a striking upregulation of genes coding for chemokines. Seventeen genes out of 50 coding for proteins with chemokine activity were upregulated including CXCL9 and IL-8 which are related to the treatment of cancer. In addition, 28 cytokine genes were upregulated including IL-1, IL-6, IL-8, IFN-
, and TNF-
. Taken together, the data suggest that Korean mistletoe lectin, in parallel with European mistletoe, has an ability to modulate human T cell function.
Styraxjaponoside A and B, Antifungal Lignan Glycosides Isolated from Styrax japonica S. et Z.
Park, Cana ; Cho, Jae-Yong ; Hwang, Bo-Mi ; Hwang, In-Sok ; Kim, Mi-Ran ; Woo, Eun-Rhan ; Lee, Dong-Gun ;
Biomolecules & Therapeutics, volume 18, issue 4, 2010, Pages 420~425
DOI : 10.4062/biomolther.2010.18.4.420
The antifungal effects and action mechanisms of styraxjaponoside A and B were investigated. Devoid of hemolytic effect, the compounds had significant effect against several human pathogenic fungal strains, with energy-independent manners. To understand the action mechanisms of the compounds, the flow cytometric analysis plotting the forward scatter and the side scatter,
(3) staining and DPH fluorescence analysis were conducted. The results indicated that the actions of the compounds were dependent upon the membrane-active mechanisms. The present study suggests that styraxjaponoside A and B exert their antimicrobial effects via membrane-disruptive mechanisms.
Effect of Mixed Extract of Panax Notoginseng, Rehmanniae Radix and Acanthopanacis Cortex (AIF) on Experimentally Induced Osteoarthritis
Park, Shin-Ae ; Kim, Jae-Hoon ; Ahn, Jeong-Taek ; Kim, Won-Tae ; Park, Chull-Gyu ; Jeong, Man-Bok ; Yi, Sun-Shin ; Yoon, Yeo-Sung ; Yoon, Jung-Hee ; Kim, Hyung-Gun ; Seo, Kang-Moon ;
Biomolecules & Therapeutics, volume 18, issue 4, 2010, Pages 426~432
DOI : 10.4062/biomolther.2010.18.4.426
The objective of the present study was to evaluate the effect of a mixed extract of three herbs, Panax Notoginseng, Rehmanniae Radix and Acanthopanacis cortex (AIF), for the treatment of horses with experimentally induced osteoarthritis. Twelve healthy male horses were included in this study. Horses were assigned to one of two groups: the AIF group (n=6) or the control group (n=6). Osteoarthritis was induced in all horses by intraarticular injection of sodium monoiodoacetate (0.12 mg/kg). Horses in the AIF group received 3 g of AIF with food daily, and those in the control group received food only. Treatment began on the day of intraarticular injection. Clinical and radiographic evaluations were performed every 2 weeks. At week 12, horses were euthanatized, and postmortem gross pathologic and histologic examinations of the middle carpal joint were performed. There were no significant differences in clinical values between the two groups. Radiographic evaluation revealed that the percentages of narrowness of joint space width in the control group were significantly higher than those in the AIF group (p<0.02). On gross pathologic examination, the mean total dimensions of articular cartilage erosions and fibrillations in the control group (
) were significantly wider than those in the AIF group (
; p<0.01). On histopathologic evaluation, significantly higher grades of staining intensity and lower empty lacunae (EL) ratios were found in the AIF group (p<0.03). The present study revealed that AIF had significant disease modifying effects in horses with experimentally induced osteoarthritis.
Anti-Gastritis and Anti-Oxidant Effects of Chenopodium album Linne Fractions and Betaine
Kim, Pit-Na ; Jeong, Choon-Sik ;
Biomolecules & Therapeutics, volume 18, issue 4, 2010, Pages 433~441
DOI : 10.4062/biomolther.2010.18.4.433
Chenopodium album Linne (CAL) is a fast-growing weedy annual plant. The leaves and young shoots may be eaten as a leafy vegetable. In oriental medicine, CAL has been used for treatment of skin disease, fever, stomach ache, toothache, and paralysis. After a preliminary screening of CAL ethanol extract and its fractions obtained from CAL leaves for anti-gastritic and anti-Helicobacter pylori (H. pylori) activity, the butanol (BuOH) fraction was found to have the most significant effect. We also examined antioxidative properties of the total CAL extract and its fractions, and also betaine as an ingredient of the BuOH fraction. To investigate the antioxidant effects of CAL on gastritis, the reducing power, free radical scavenging activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH), and lipid peroxidation effects were determined. Additionally, the BuOH fraction reduced cell viability in a concentration dependent manner in human gastric cancer cell lines. The results of this study revealed that CAL has excellent antioxidant activity, and may be useful in treating gastritis and gastric cancer.
The Inhibitory Effect of Eupatilin on the Intestinal Contraction Induced by Carbachol
Je, Hyun-Dong ; Lee, Jong-Min ; La, Hyen-Oh ;
Biomolecules & Therapeutics, volume 18, issue 4, 2010, Pages 442~447
DOI : 10.4062/biomolther.2010.18.4.442
This study was conducted to determine whether treatment with the anti-inflammatory eupatilin influences intestinal smooth muscle contraction stimulated by carbachol and, if so, to investigate the related mechanism. Denuded ileal or colonic muscles from Sprague-Dawley rats were used for the study and measurements of isometric contractions were obtained using a computerized data acquisition system; this data was also combined with results from molecular experiments. Eupatilin from Artemisia asiatica Nakai significantly decreased carbachol-induced contractions in both ileal and colonic muscles. Interestingly, eupatilin decreased carbachol-induced phosphorylation of ERK1/2 more significantly than that of MYPT1 at Thr855 in ileal and colonic muscles. However, eupatilin significantly decreased phosphorylation of MYPT1 at Thr855, but only in ileal muscle. Therefore, thin filament regulation, including MEK inactivation and related phospho-ERK1/2 decrease, is mainly involved in the eupatilin-induced decrease of intestinal contraction induced by carbachol. In conclusion, this study provides the evidence and a possible related mechanism concerning the inhibitory effect of the flavonoid as an antispasmodic on the agonist-induced contractions in rat ileum and colonic muscles.
Inhibitory Effect of Nicardipine on hERG Channel
Chung, Eun-Yong ; Cho, Hea-Young ; Cha, Ji-Hun ; Kwon, Kyoung-Jin ; Jeon, Seol-Hee ; Jo, Su-Hyun ; Kim, Eun-Jung ; Kim, Hye-Soo ; Chung, Hye-Ju ;
Biomolecules & Therapeutics, volume 18, issue 4, 2010, Pages 448~453
DOI : 10.4062/biomolther.2010.18.4.448
Drug-induced long QT syndrome is known to be associated with the onset of torsades de pointes (TdP), resulting in a fatal ventricular arrhythmia. QT interval prolongation can result from blocking the human ether-a-go-go-related gene (hERG) channel, which is important for the repolarization of cardiac action potential. Nicardipine, a Ca-channel blocker and antihypertensive agent, has been reported to increase the risk of occasional serious ventricular arrhythmias. We studied the effects of nicardipine on hERG
channels expressed in HEK293 cells and Xenopus oocytes. The cardiac electrophysiological effect of nicardipine was also investigated in this study. Our results revealed that nicardipine dose-dependently decreased the tail current of the hERG channel expressed in HEK293 cells with an
. On the other hand, nicardipine did not affect hERG channel trafficking. Taken together, nicardipine inhibits the hERG channel by the mechanism of short-term channel blocking. Two S6 domain mutations, Y652A and F656A, partially attenuated (Y652A) or abolished (F656A) the hERG current blockade, suggesting that nicardipine blocks the hERG channel at the pore of the channel.
Neuroprotective Effects of Carpinus tschonoskii MAX on 6-Hydroxydopamine-Induced Death of PC12 Cells
Kim, Min-Kyoung ; Kim, Sang-Cheol ; Kang, Jung-Il ; Boo, Hye-Jin ; Hyun, Jin-Won ; Koh, Young-Sang ; Park, Deok-Bae ; Yoo, Eun-Sook ; Kang, Ji-Hoon ; Kang, Hee-Kyoung ;
Biomolecules & Therapeutics, volume 18, issue 4, 2010, Pages 454~462
DOI : 10.4062/biomolther.2010.18.4.454
The present study investigated the neuroprotective effect of Carpinus tschonoskii MAX and its intracellular protective mechanism on 6-hydroxydopamine (6-OHDA)-induced oxidative damage in PC12 cells. We found that pretreatment of PC12 cells with C. tschonoskii extract significantly inhibited the cell death induced by 6-OHDA in a dose dependent manner. C. tschonoskii extract decreased 6-OHDA-induced apoptotic events such as chromatin condensation, DNA fragmentation, the decrease of Bcl-2/Bax ratio, caspase-3 activation and PARP cleavage. C. tschonoskii extract also reduced generation of 6-OHDA-induced reactive oxygen species and nitric oxide. Furthermore, C. tschonoskii extract up-regulated the myocyte enhancer factor 2 D (MEF2D), a critical transcription factor for neuronal survival, and Akt activity, whereas it inhibited the activity of ERK1/2 and JNK. The results suggest that C. tschonoskii extract decreases 6-OHDA-induced oxidative stress and could prevent PC12 cell apoptosis induced by 6-OHDA via the up-regulation of MEF2D and Akt activity, and thus may have application in developing therapeutic agents for Parkinson's disease.
Effects of Anti-B7.1/B7.2 Antibodies on LPS-Stimulated Macrophages
Won, Tae-Joon ; Huh, Yoon-Joo ; Lim, Young-Tae ; Song, Dong-Sup ; Hwang, Kwang-Woo ;
Biomolecules & Therapeutics, volume 18, issue 4, 2010, Pages 463~468
DOI : 10.4062/biomolther.2010.18.4.463
T-cell activation depends on signals received by the T-cell receptor and CD28 co-stimulatory receptor. Since B7.1 and B7.2 molecules expressed on the surface of antigen presenting cells provide co-stimulatory signals through CD28 to T-cells, an inhibitor of CD28-B7.1/B7.2 binding has been proposed as a therapeutic agent for suppression of excessive T-cell activity. Although anti-B7.1/B7.2 antibodies are known to block B7.1 and B7.2 molecules, their effects on intracellular events in antigen presenting cells remain unclear. In this study, anti-B7.1/B7.2 antibodies decreased secretion of nitric oxide and pro-inflammatory cytokines such as TNF-
, and IL-12 in LPS-activated RAW264.7 macrophage-like cells and peritoneal macrophages. Moreover, anti-B7.1/B7.2 antibodies inhibited
phosphorylation and down-regulated expression of co-stimulatory molecules including B7.1, B7.2, and PD-L1 in LPS-stimulated peritoneal macrophages. These findings suggest that CTLA4-Ig and anti-B7.1/B7.2 antibodies may be candidates to treat chronic inflammatory diseases and autoimmune responses caused by excessive activation of both T-cells and macrophages.
The Promotive Effects of Antioxidative Apigenin on the Bioavailability of Paclitaxel for Oral Delivery in Rats
Choi, Sang-Joon ; Choi, Jun-Shik ;
Biomolecules & Therapeutics, volume 18, issue 4, 2010, Pages 469~476
DOI : 10.4062/biomolther.2010.18.4.469
This study was to investigate the effect of apigenin on the bioavailability of paclitaxel after oral and intravenous administration in rats. The effect of apigenin on P-glycoprotein (P-gp), cytochrome P450 (CYP)3A4 activity was evaluated. The pharmacokinetic parameters of paclitaxel were determined in rats after oral (40 mg/kg) or intravenous (5 mg/kg) administration of paclitaxel with apigenin (0.4, 2 and 8 mg/kg) to rats. Apigenin inhibited CYP3A4 activity with 50% inhibition concentration (
) of 1.8
. In addition, apigenin significantly inhibited P-gp activity. Compared to the control group, apigenin significantly increased the area under the plasma concentration-time curve (AUC, p<0.05 by 2 mg/kg, 59.0% higher; p<0.01 by 8 mg/kg, 87% higher) of oral paclitaxel. Apigenin also significantly (p<0.05 by 2 mg/kg, 37.2% higher; p<0.01 by 8 mg/kg, 59.3% higher) increased the peak plasma concentration (
) of oral paclitaxel. Apigenin significantly increased the terminal half-life (
, p<0.05 by 8 mg/kg, 34.5%) of oral paclitaxel. Consequently, the absolute bioavailability (A.B.) of paclitaxel was significantly (p<0.05 by 2 mg/kg, p<0.01 by 8 mg/kg) increased by apigenin compared to that in the control group, and the relative bioavailability (R.B.) of oral paclitaxel was increased by 1.14- to 1.87-fold. The pharmacokinetics of intravenous paclitaxel were not affected by the concurrent use of apigenin in contrast to the oral administration of paclitaxel. Accordingly, the enhanced oral bioavailability by apigenin may be mainly due to increased intestinal absorption caused via P-gp inhibition by apigenin rather than to reduced renal and hepatic elimination of paclitaxel. The increase in the oral bioavailability might be mainly attributed to enhanced absorption in the gastrointestinal tract via the inhibition of P-gp and reduced first-pass metabolism of paclitaxel via the inhibition of the CYP3A subfamily in the small intestine and/or in the liver by apigenin. It appears that the development of oral paclitaxel preparations as a combination therapy is possible, which will be more convenient than the i.v. dosage form.