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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Biomolecules & Therapeutics
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The Korean Society of Applied Pharmacology
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Volume & Issues
Volume 19, Issue 4 - Oct 2011
Volume 19, Issue 3 - Jul 2011
Volume 19, Issue 2 - Apr 2011
Volume 19, Issue 1 - Jan 2011
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Platform Technologies for Research on the G Protein Coupled Receptor: Applications to Drug Discovery Research
Lee, Sung-Hou ;
Biomolecules & Therapeutics, volume 19, issue 1, 2011, Pages 1~8
DOI : 10.4062/biomolther.2011.19.1.001
G-protein coupled receptors (GPCRs) constitute an important class of drug targets and are involved in every aspect of human physiology including sleep regulation, blood pressure, mood, food intake, perception of pain, control of cancer growth, and immune response. Radiometric assays have been the classic method used during the search for potential therapeutics acting at various GPCRs for most GPCR-based drug discovery research programs. An increasing number of diverse small molecules, together with novel GPCR targets identified from genomics efforts, necessitates the use of high-throughput assays with a good sensitivity and specificity. Currently, a wide array of high-throughput tools for research on GPCRs is available and can be used to study receptor-ligand interaction, receptor driven functional response, receptor-receptor interaction,and receptor internalization. Many of the assay technologies are based on luminescence or fluorescence and can be easily applied in cell based models to reduce gaps between in vitro and in vivo studies for drug discovery processes. Especially, cell based models for GPCR can be efficiently employed to deconvolute the integrated information concerning the ligand-receptor-function axis obtained from label-free detection technology. This review covers various platform technologies used for the research of GPCRs, concentrating on the principal, non-radiometric homogeneous assay technologies. As current technology is rapidly advancing, the combination of probe chemistry, optical instruments, and GPCR biology will provide us with many new technologies to apply in the future.
Neuroadaptations Involved in Long-Term Exposure to ADHD Pharmacotherapies: Alterations That Support Dependence Liability of These Medications
Dela Pena, Ike C. ; Ahn, Hyung-Seok ; Shin, Chan-Young ; Cheong, Jae-Hoon ;
Biomolecules & Therapeutics, volume 19, issue 1, 2011, Pages 9~20
DOI : 10.4062/biomolther.2011.19.1.009
Repeated administration of addictive drugs causes cellular and molecular changes believed to be the mechanism of pro-addictive behaviors. Neuroadaptations also take place with repeated administration of amphetamine, methylphenidate and atomoxetine, drugs for Attention Deficit Hyperactivity Disorders (ADHD), and it is speculated that these changes may serve as markers to demonstrate the dependence liability of these therapies. In this review, we enumerate the neuroadaptive changes in molecules associated with neuronal signaling and plasticity, as well as neuronal morphology wrought by repeated administration of ADHD medications. We provide the current perspective on the dependence liability of these therapies, and also suggest of some factors that need to be considered in future investigations, so that what is drawn from animal studies would be better consolidated with those known clinically.
Ceramide Induces Apoptosis and Growth Arrest of Human Glioblastoma Cells by Inhibiting Akt Signaling Pathways
Lee, Eun-Chang ; Lee, Young-Seok ; Park, Na-Hee ; So, Kwang-Sup ; Chun, Young-Jin ; Kim, Mie-Young ;
Biomolecules & Therapeutics, volume 19, issue 1, 2011, Pages 21~26
DOI : 10.4062/biomolther.2011.19.1.021
Ceramide is an important lipid mediator of extracellular signals that control various cellular functions, including apoptosis. In this study, we showed that ceramide induced apoptosis in U373MG human glioblastoma cells associated with G1 cell cycle arrest. Treatment of cells with ceramide increased proapoptotic Bax expression and inhibited the expression of antiapoptotic Bcl-2 and Bcl-xL Ceramide also downregulated cyclin E, cyclin D1, cdk 2, and cdk4 which are involved in regulating cell cycle. In addition, ceramide suppressed phosphorylation of Akt, Bad, p70 S6 kinase, and 4E-BP1, suggesting the involvement of Akt/mTOR signaling pathway. Additionally, okadaic acid, an inhibitor of protein phosphatase 2A, partially blocked the ceramide mediated inhibition of phosphorylation of Akt and 4E-BP1. These results suggest that ceramide induces apoptosis in U373MG glioblastoma cells by regulating multiple signaling pathways that involve cell cycle arrest associated with Akt signaling pathway.
Quercetin Derivatives from Siegesbeckia glabrescens Inhibit the Expression of COX-2 Through the Suppression of NF-κB Activation in Microglia
Lim, Hyo-Jin ; Li, Hua ; Kim, Jae-Yeon ; Ryu, Jae-Ha ;
Biomolecules & Therapeutics, volume 19, issue 1, 2011, Pages 27~32
DOI : 10.4062/biomolther.2011.19.1.027
The activation of microglia induces the overproduction of inflammatory mediators that are responsible for the neurodegenerative disorders including Alzheimer's disease and Parkinson's disease. The large amounts of prostaglandin
) produced by inducible cyclooxygenase (COX-2) is one of the main inflammatory mediators that can contribute to neurodegeneration. The inhibition of COX-2 thus may provide therapeutic strategy for the treatment of neurodegenerative diseases. From the activity-guided purification of EtOAc soluble fraction of Siegesbeckia glabrescens, four compounds were isolated as inhibitors of
production in LPS-activated microglia. Their structures were determined as 3, 4'-dimethylquercetin (1), 3, 7-dimethylquercetin (2), 3-methylquercetin (3) and 3, 7, 4'-trimethylquercetin (4) by the mass and NMR spectral data analysis. The compounds 1-4 showed dose-dependent inhibition of
production in LPS-activated microglia with their
values of 7.1, 4.9, 4.4,
respectively. They reduced the expression of protein and mRNA of COX-2 through the inhibition of I-
degradation and NF-
activity that were correlated with the inactivation of p38 and ERK. Therefore the active compounds from Siegesbeckia glabrescens may have therapeutic effects on neuro-inflammatory diseases through the inhibition of overproduction of
and suppression of COX-2 overexpression.
Decursin from Angelica gigas Nakai Blocks hKv1.5 Channel
Kwak, Yong-Geun ; Choi, Bok-Hee ; Kim, Dae-Keun ; Eun, Jae-Soon ;
Biomolecules & Therapeutics, volume 19, issue 1, 2011, Pages 33~37
DOI : 10.4062/biomolther.2011.19.1.033
Decursin was purified from Angelica gigas Nakai, and its effects on the human Kv1.5 (hKv1.5) currents were recorded in mouse fibroblasts (
cells) by whole-cell patch-clamp technique. Decursin inhibited hKv1.5 current in a concentration-dependent manner, with an
at +60 mV. Decursin accelerated the inactivation kinetics of the hKv1.5 channel, and slowed the deactivation kinetics of the hKv1.5 current, resulting in a tail crossover phenomenon. Also, decursin inhibited the hKv1.5 current in a use-dependent manner. These results strongly suggest that decursin is a kind of open-channel blocker of the hKv1.5 channel.
Identification of Urinary Biomarkers Related to Cisplatin-Induced Acute Renal Toxicity Using NMR-Based Metabolomics
Wen, He ; Yang, Hye-Ji ; Choi, Myung-Joo ; Kwon, Hyuk-Nam ; Kim, Min-Ah ; Hong, Soon-Sun ; Park, Sung-Hyouk ;
Biomolecules & Therapeutics, volume 19, issue 1, 2011, Pages 38~44
DOI : 10.4062/biomolther.2011.19.1.038
Cisplatin is widely used for various types of cancers. However, its side effects, most notably, renal toxicity often limit its clinical utility. Although previous metabolomic studies reported possible toxicity markers, they used small number of animals and statistical approaches that may not perform best in the presence of intra-group variation. Here, we identified urinary biomarkers associated with renal toxicity induced by cisplatin using NMR-based metabolomics combined with Orthogonal Projections to Latent Structures-Discriminant Analysis (OPLS-DA). Male Sprague-Dawley rats (n=22) were treated with cisplatin (10 mg/kg single dose), and the urines obtained before and after treatment were analyzed by NMR. Multivariable analysis of NMR data presented clear separation between non-treated and treated groups. The OPLS-DA statistical results revealed that 1,3-dimethylurate, taurine, glucose, glycine and branched-chain amino acid (isoleucine, leucine and valine) were significantly elevated in the treated group and that phenylacetylglycine and sarcosine levels were decreased in the treated group. To test the robustness of the approach, we built a prediction model for the toxicity and were able to predict all the unknown samples (n=14) correctly. We believe the proposed NMR-based metabolomics with OPLS-DA approach and the resulting urine markers can be used to augment the currently available blood markers.
Markers in Morphine- and Cocaine-Addicted Animals
Hu, Zhenzhen ; Park, Kwang-Soon ; Han, Jin-Yi ; Jang, Choon-Gon ; Oh, Sei-Kwan ; Kim, Hyoung-Chun ; Yang, Chae-Ha ; Kim, Eun-Jeong ; Oh, Ki-Wan ;
Biomolecules & Therapeutics, volume 19, issue 1, 2011, Pages 45~51
DOI : 10.4062/biomolther.2011.19.1.045
These experiments were designed to use typical makers from behaviors and molecular basis in addicted animals of morphine and cocaine. Morphine has been widely abused with a high physical dependence liability. Morphine withdrawal activates the intracellular cAMP signaling pathway and further leads to changes in the expression of the cAMP response element binding protein (CREB), which may be important to the development and expression of morphine dependence. From these experiments, repeated morphine (10 mg/kg, twice per day for 7 days) developed physical dependence. Withdrawal signs were precipitated by naloxone and also increased the expression of the CREB. In addition, repeated exposure of cocaine (15 mg/kg) to mice develops locomotor sensitization and produced lasting behavioral sensitivity. Cocaine- and amphetamine-regulated transcript peptide (CART) peptide was up-regulated by repeated administration of cocaine in the striatum. Therefore, repeated morphine induced the development of physical dependence and increased pCREB. In addition, repeated cocaine induced locomotor sensitization and over-expressed CART peptide. In conclusion, the development of physical dependence and pCREB for morphine, and locomotor sensitization and CART peptide over-expression for cocaine would be useful markers to predict the abuse potential of opioid analgesics and pychostimulant drugs in animals, respectively.
Evaluation of Anti-Colitic Effect of Chung-Jang-Hwan (C-mix) in Mice
Lee, Ho-Yong ; Ahn, Young-Tae ; Park, Se-Hoon ; Ahn, Young-Min ; Shim, Jae-Jung ; Lee, Jung-Hee ; Lee, Jeong-Sang ; Surh, Young-Joon ; Huh, Chul-Sung ; Kim, Dong-Hyun ;
Biomolecules & Therapeutics, volume 19, issue 1, 2011, Pages 52~58
DOI : 10.4062/biomolther.2011.19.1.052
The inhibitory effect of Chung-Jang-Hwan (C-mix) consisted of Geranium nepalense subsp. thunbergii, Saururus chinensis, and Rubus coreanus were investigated in dextran sulfate sodium (DSS)-induced colitic mice by microarray analysis. Treatment with Cmix improved colitic symptoms, including colon shortening and myeloperoxidase activity. Treatment with DSS alone upregulated the expression levels of inflammation-related genes, including IL-
, IL-6, CCL2, CCL4, CCL5, CCL7, CCL8, CCL24, CXCL1, CXCL2, CXCL5, CXCL9 and CXCL10, and other colitis-related genes such as COX-2, PAP, MMP family, S100a8, S100a9 and DEFA1 in mice. However, treatment with C-mix inhibited the expression levels of inflammation-associated genes induced by DSS. The increased expression levels of COX-2 and IL-
, representative inflammatory genes, were confirmed by a quantitative realtime polymerase chain reaction analysis. These results indicate that C-mix may ameliorate colitis by the inhibitory regulation of inflammation-associated genes.
Evaluation of Immunotoxicity of Shizukaol B Isolated from Chloranthus japonicus
Kwon, Soon-Woo ; Kim, Young-Kook ; Kim, Jee-Youn ; Ryu, Hwa-Sun ; Lee, Hong-Kyung ; Kang, Jong-Soon ; Kim, Hwan-Mook ; Hong, Jin-Tae ; Kim, Young-Soo ; Han, Sang-Bae ;
Biomolecules & Therapeutics, volume 19, issue 1, 2011, Pages 59~64
DOI : 10.4062/biomolther.2011.19.1.059
Dimeric sesquiterpenoid shizukaol B (SKB) was isolated from Chloranthus japonicus Sieb. Except that SKB inhibited adhesion molecule expression in monocytes and endothelial cells, no more biological and pharmacological activity of SKB had been reported until now. In this study, we examined immunosuppressive activity of SKB. SKB strongly inhibited lipopolysaccharide (LPS)-induced B cell proliferation with
of 137 ng/ml, but slightly or not concanavalin A-induced T cell proliferation, LPS-induced macrophage NO production, and LPS-induced dendritic cell maturation. As a mechanism, SKB strongly induced apoptotic death of B cells, but not other cell types. These results suggested that SKB induced toxicity-mediated immunosuppression against B cells.
Effect of Ambroxol on Secretion, Production and Gene Expression of Mucin from Cultured Airway Epithelial Cells
Lee, Hyun-Jae ; Lee, Su-Yel ; Cho, Kyoung-Rai ; Jeon, Byeong-Kyou ; Lee, Jae-Woo ; Bae, Heung-Seog ; Lee, Choong-Jae ;
Biomolecules & Therapeutics, volume 19, issue 1, 2011, Pages 65~69
DOI : 10.4062/biomolther.2011.19.1.065
In this study, we investigated whether ambroxol significantly affects secretion, production and gene expression of mucin from cultured airway epithelial cells. Confluent primary rat tracheal surface epithelial (RTSE) cells were pretreated with adenosine triphosphate (ATP) for 5 min and then treated for 30 min with ambroxol to assess the effect on mucin secretion using ELISA. Additionally, confluent NCI-H292 cells were pretreated with ambroxol for 30 min and then stimulated with EGF or PMA for 24 h. The MUC5AC mucin gene expression and mucin protein production were measured by RT-PCR and ELISA. The results were as follows: (1) ambroxol did not significantly affect ATP-induced mucin secretion from cultured RTSE cells; (2) ambroxol inhibited the production of MUC5AC mucin protein induced by EGF and PMA in NCI-H292 cells; (3) ambroxol also inhibited the expression of MUC5AC mucin gene induced by EGF and PMA in NCI-H292 cells. This result suggests that ambroxol can inhibit the production and gene expression of MUC5AC mucin, by directly acting on human airway epithelial cells.
Ethyl Docosahexaenoate and Its Acidic Form Increase Bone Formation by Induction of Osteoblast Differentiation and Inhibition of Osteoclastogenesis
Choi, Bo-Yun ; Eun, Jae-Soon ; Nepal, Manoj ; Lee, Mi-Kyung ; Bae, Tae-Sung ; Kim, Byung-Il ; Soh, Yun-Jo ;
Biomolecules & Therapeutics, volume 19, issue 1, 2011, Pages 70~76
DOI : 10.4062/biomolther.2011.19.1.070
Bone remodeling is a dynamic process involving a constant balance between osteoclast-induced bone resorption and osteoblast-induced bone formation. Osteoclasts play a crucial homeostatic role in skeletal modeling and remodeling, and destroy bone in many pathological conditions. Previously, we reported that the hexane soluble fraction of Ficus carica inhibited osteoclast differentiation. Poly unsaturated fatty acids, such as ethyl docosahexaenoate (E-DHA), docosahexaenoic acid (DHA), cis-11,14-eicosadienoic acid (EDA) and eicosapentaenoic acid (EPA), were identified from the hexane soluble fraction of Ficus carica. Among them, E-DHA most potently inhibited osteoclastogenesis in RAW264.7 cells. E-DHA reduced the activities of JNK and NF-
. E-DHA suppressed the expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1). Interestingly, DHA increased the activity of alkaline phosphatase and expression of bone morphogenetic protein 2 (BMP2) more than E-DHA in MC3T3-E1 cells, suggesting that DHA may induce osteoblast differentiation. The data suggests that a combination of E-DHA and DHA has potential use in the treatment of diseases involving abnormal bone lysis, such as osteoporosis, rheumatoid arthritis and periodontal bone erosion.
Sulforaphane Enhances MHC Class II-Restricted Presentation of Exogenous Antigens
Shin, Seul-Mee ; Jung, Ki-Sung ; Park, Yoon-Hee ; Ko, Young-Wook ; Lee, Chong-Kil ; Cho, Kyung-Hae ; Ha, Nam-Joo ; Kim, Kyung-Jae ;
Biomolecules & Therapeutics, volume 19, issue 1, 2011, Pages 77~83
DOI : 10.4062/biomolther.2011.19.1.077
Sulforaphane is an isothiocyanate found in cruciferous vegetables that has been reported to be an effective cancer preventive agent inducing growth arrest and/or cell death in cancer cells of various organs. This paper reports that sulforaphane exerts immunomodulatory activity on the MHC-restricted antigen presenting function. Sulforaphane efficiently increased the class II-restricted presentation of an exogenous antigen, ovalbumin (OVA), in both dendritic cells (DCs) and peritoneal macrophages in vitro. The class II-restricted OVA presentation-enhancing activity of sulforaphane was also confirmed using mice that had been injected with sulforaphane followed by soluble OVA. On the other hand, sulforaphane did not affect the class I-restricted presentation of exogenous OVA at concentrations that increase the class II-restricted antigen presentation. At a high concentration (
), sulforaphane inhibited the class I-restricted presentation of exogenous OVA. Sulforaphane did not affect the phagocytic activity of the DCs, and the cell surface expression of total H-
, B7-1, B7-2 and CD54 molecules, even though it increased the expression of I-
molecules to a barely discernable level. These results show that sulforaphane increases the class II-restricted antigen presenting function preferentially, and might provide a novel insight into the mechanisms of the anti-cancer effects of sulforaphane.
Synergic Effect of Trimebutine Combined with Mosapride on Gastrointestinal Dysfunction and Visceral Pain Induced in Stress Models
Park, Young-Joon ; Park, Yong-Sul ; Chung, Zoo-Chul ; Nam, Yun-Sung ; Chung, Yoon-Hee ; Cho, Kwan-Hyung ; Choi, Sung-Up ; Sohn, Uy-Dong ; Park, Eon-Sub ; Je, Hyun-Dong ; Lee, Choong-Ho ; Lee, Moo-Yeol ; Jeong, Ji-Hoon ;
Biomolecules & Therapeutics, volume 19, issue 1, 2011, Pages 84~89
DOI : 10.4062/biomolther.2011.19.1.084
The present study was undertaken to determine whether combined treatment with prokinetic trimebutine and mosapride has a synergic effect on gastrointestinal motility and visceral pain associated with gastrointestinal dysfunction. To develop effective gastroprokinetic agents with greater potencies than trimebutine or mosapride for the treatment of gastrointestinal tract disease, a mixture of trimebutine and mosapride was designed and prepared. In the present study, treatment with trimebutine alone showed a dose-dependent effect on propelling movements of normal small and large intestine in mice, whereas mosapride effected only small intestine motility. Co-administration of trimebutine with mosapride, a well-established prokinetic drug, produced a synergistic influence on normal small intestine motility, but demonstrated an unclear effect on large intestine motility, with a slight tendency to reduce the propelling time. In a stress model, the small and large intestine motilities were significantly decreased. The reduction of intestine motility was restored to a normal level and the restoring effect was more pronounced in the combined treatment with trimebutine plus mosapride than treatment with trimebutine or mosapride alone. Furthermore, treatment with trimebutine plus mosapride significantly decreased acute visceral pain which was not controlled by trimebutine or mosapride alone. These data suggest that combination therapy with trimebutine plus mosapride has a synergic effect on small and large intestine motility and visceral pain control in gastrointestinal disorders.
Rapid Identification of Bioactive Compounds Reducing the Production of Amyloid β-Peptide (Aβ) from South African Plants Using an Automated HPLC/SPE/HPLC Coupling System
Kwon, Hak-Cheol ; Cha, Jin-Wook ; Park, Jin-Soo ; Chun, Yoon-Sun ; Moodley, Nivan ; Maharaj, Vinesh J. ; Youn, Sung-Hee ; Chung, Sung-Kwon ; Yang, Hyun-Ok ;
Biomolecules & Therapeutics, volume 19, issue 1, 2011, Pages 90~96
DOI : 10.4062/biomolther.2011.19.1.090
Automated HPLC/SPE/HPLC coupling experiments using the Sepbox system allowed the rapid identification of four bioactive principles reducing the production of amyloid
) from two South African plants, Euclea crispa subsp. crispa and Crinum macowanii. The structures of biologically active compounds isolated from the methanol extract of Euclea crispa subsp. crispa were assigned as 3-oxo-oleanolic acid (1) and natalenone (2) based on their NMR and MS data, while lycorine (3) and hamayne (4) were isolated from the dichloromethane-methanol (1:1) extract of Crinum macowanii. These compounds were shown to inhibit the production of
from HeLa cells stably expressing Swedish mutant form of amyloid precursor protein (APPsw).
Polyacetylene Compound from Cirsium japonicum var. ussuriense Inhibits the LPS-Induced Inflammatory Reaction via Suppression of NF-κB Activity in RAW 264.7 Cells
Kang, Tae-Jin ; Moon, Jung-Sun ; Lee, Sook-Yeon ; Yim, Dongs-Sool ;
Biomolecules & Therapeutics, volume 19, issue 1, 2011, Pages 97~101
DOI : 10.4062/biomolther.2011.19.1.097
Cirsium japonicum var. ussuriense is known to have a variety of biological activities, including anti-inflammatory, analgesic activity and antipyretic activity. In this study we investigated the role of polyacetylene compound, 1-Heptadecene-11, 13-diyne-8, 9, 10-triol (PA) from the root of Cirsium japonicum var. ussuriense as an immune-modulator. PA was evaluated as inhibitors of some macrophage functions involved in the inflammatory process. We tested the effect of PA on the production of pro-inflammatory cytokines, interleukin-1beta (IL-
) and tumor necrosis factor-alpha (TNF-
), and nitric oxide (NO) in murine macrophage cell line, RAW264.7. There was no effect on cytokine production of macrophages by PA itself. However, PA inhibited lipopolysaccharide (LPS)-induced IL-
production by macrophages at a dose dependent manner. PA also suppressed the NO production of macrophages by LPS. LPS-induced NF-
activity was decreased by treatment of PA. Therefore, these results suggest that PA has anti-inflammatory effect by inhibiting the NF-
Essential Oil of Thujopsis dolobrata Suppresses Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice
Nam, Kung-Woo ; Noh, Jae-Kyu ; Kim, Su-Kwan ; Lee, Sung-Jin ; Kim, Kyeong-Ho ; Oh, Ki-Bong ; Shin, Jong-Heon ; Mar, Woong-Chon ;
Biomolecules & Therapeutics, volume 19, issue 1, 2011, Pages 102~108
DOI : 10.4062/biomolther.2011.19.1.102
We examined the effects of essential oil from Thujopsis dolobrata Sieb. et Zucc. var. hondai Makino (EOTD) (Cupressaceae) on atopic dermatitis (AD)-like skin lesions in NC/Nga mice. Treatment with EOTD twice daily for two weeks ameliorate AD-like skin lesions induced by DNCB (2,4 dinitrochlorobenzene), and clinical scores were reduced to 7.29, 7.07, and 4.5 points in the groups treated with 1.5%, 3.0%, and 6.0% extract (p<0.01) respectively, from the 15.0 score obtained using vehicle. EOTD inhibited the infiltration of mast cells into the AD-like skin lesion in NC/Nga mice (p<0.01) and also reduced serum histamine and IgE levels (p<0.05). Furthermore, it dose-dependently inhibited the release of beta-hexosaminidase from rat basophilic leukemia RBL 2H3 cells. These results indicate that EOTD reduces AD-like skin lesions by inhibiting the production of IgE and histamine, and, thus, IgE-mediated degranulation.
Effect of Polyoxyethylene Alkyl Esters on Permeation Enhancement and Impedance of Skin
Kim, Hee-Sun ; Oh, Seaung-Youl ;
Biomolecules & Therapeutics, volume 19, issue 1, 2011, Pages 109~117
DOI : 10.4062/biomolther.2011.19.1.109
In this work, we have investigated the effect of polyoxyethylene alkyl ester nonionic surfactants on percutaneous permeation enhancement of a model drug, ketoprofen. We also investigated the mechanism involved in the enhancement using impedance and solubility measurement. Three groups of nonionic surfactants with different ethylene oxide content were studied. The permeation results showed that all surfactants enhanced the percutaneous absorption, irrespective of the molecular weight. The permeation results from PEG-45 monostearate (PEGMS45) were rather unexpected. Impedance and solubility results indicate that the mechanism involved in the enhancement of permeation by PEG-10 monooleate (PEGMO10) and PEGMS45 is rather different. The results from PEGMS45 suggest that it could be a potential candidate as a skin penetration enhancer with high molecular weight, which may poses less skin irritation and systemic side effect than the smaller surfactant molecules. Overall, this work provided some useful information on percutaneous transport enhancement and the mechanistic insights involved in skin permeation for these nonionic surfactants.
Neuroprotective Effect of the n-Hexane Extracts of Laurus nobilis L. in Models of Parkinson's Disease
Ham, Ah-Rom ; Shin, Jong-Heon ; Oh, Ki-Bong ; Lee, Sung-Jin ; Nam, Kung-Woo ; Koo, Uk ; Kim, Kyeong-Ho ; Mar, Woong-Chon ;
Biomolecules & Therapeutics, volume 19, issue 1, 2011, Pages 118~125
DOI : 10.4062/biomolther.2011.19.1.118
Free radical scavenging and antioxidants have attracted attention as a way to prevent the progression of Parkinson's disease (PD). This study was carried out to investigate the effects of n-hexane fraction from Laurus nobilis L. (Lauraceae) leaves (HFL) on dopamine (DA)-induced intracellular reactive oxygen species (ROS) production and apoptosis in human neuroblastoma SH-SY5Y cells. Compared with apomorphine (APO,
) as a positive control, the HFL
value for DA-induced apoptosis was
, and two major compounds from HFL, costunolide and dehydrocostus lactone, were
, respectively. HFL and these major compounds significantly inhibited ROS generation in DA-induced SH-SY5Y cells. A rodent 6-hydroxydopamine (6-OHDA) model of PD was employed to investigate the potential neuroprotective effects of HFL in vivo. 6-OHDA was injected into the substantia nigra of young adult rats and an immunohistochemical analysis was conducted to quantitate the tyrosine hydroxylase (TH)-positive neurons. HFL significantly inhibited 6-OHDA-induced TH-positive cell loss in the substantia nigra and also reduced DA induced
-synuclein (SYN) formation in SH-SY5Y cells. These results indicate that HFL may have neuroprotective effects against DA-induced in vitro and in vivo models of PD.
Fatty Acid Components of Hardy Kiwifruit (Actinidia arguta) as IL-4 Production Inhibitor
Park, Hye-Min ; Son, Mi-Won ; Kim, Dong-Hyun ; Kim, Seon-Hee ; Kim, Sung-Hoon ; Kwon, Hak-Cheol ; Kim, Sun-Yeou ;
Biomolecules & Therapeutics, volume 19, issue 1, 2011, Pages 126~133
DOI : 10.4062/biomolther.2011.19.1.126
The fruit of Actinidia arguta (AA) has been used mainly for the treatment of skin diseases, diuresis, diabetes mellitus and osteoporosis in Korean traditional medicine. It is known that AA (hardy kiwi) fruit extract has an effect on 2-chloro-1,3,5-trinitrobenzene-induced atopic dermatitis-like skin lesions in NC/Nga mice. Mode of action for it is associated with the modulation of biphasic Th1/Th2 cytokines. Furthermore, DA9102 containing AA is a herbal medicine currently under phase II clinical trial for atopic dermatitis in Korea. However, no active principles of AA on the decrease of Th2 cytokines including IL-4 and IL-10 have been identified. In this study, bioactivity-guided fractionation of an alcohol extract from the dried fruits of AA using ELISA assay for IL-4 production led to the isolation of
-linolenic acid (I), linoleic acid (II), ethyl linolenate (III), ethyl linoleate (IV) and ethyl stearate (V) as the major active components. These compounds showed the down-regulatory effects of IL-4 production in A23187-stimulated RBL-2H3 cells without cytotoxicity.
Effects of Synthetic Pseudoceramides on Sphingosine Kinase Activity in F9-12 Cells
Jin, You-Xun ; Shin, Kyong-Oh ; Park, Myung-Yong ; Lee, Shin-Hee ; Park, Byeong-Deog ; Oh, Sei-Kwan ; Yoo, Hwan-Soo ; Lee, Yong-Moon ;
Biomolecules & Therapeutics, volume 19, issue 1, 2011, Pages 134~139
DOI : 10.4062/biomolther.2011.19.1.134
Sphingosine kinase (SPHK) has a central role to control cell death and cell proliferation, which is suggested as a sphingolipid rheostat by regulating the levels between ceramide and sphingosine 1-phosphate (S1P). Therefore, physiological regulators of SPHK will be a good candidate to develop a new targeted drug. For this purpose, a series of synthetic pseudoceramides were tested by SPHK assay either cell-based or cell-free system. K10PC-5 strongly inhibited SPHK, while K6PC-5 activated SPHK in cell-free system. Specifically, K6PC-5 activated SPHK under the co-treatment with
dimethylsphingosine (DMS), a SPHK inhibitor. Collectively, we developed a simple SPHK assay system to find SPHK regulatory pseudoceramide compounds, K10PC-5 and K6PC-5 which may be useful to cancer treatment or immune regulation like FTY720, a synthetic sphingolipid mimetic compound.