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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
> Journal Vol & Issue
Biomolecules & Therapeutics
Journal Basic Information
Journal DOI :
The Korean Society of Applied Pharmacology
Editor in Chief :
Volume & Issues
Volume 22, Issue 6 - Nov 2014
Volume 22, Issue 5 - Sep 2014
Volume 22, Issue 4 - Jul 2014
Volume 22, Issue 3 - May 2014
Volume 22, Issue 2 - Mar 2014
Volume 22, Issue 1 - Jan 2014
Selecting the target year
VEGF-VEGFR Signals in Health and Disease
Shibuya, Masabumi ;
Biomolecules & Therapeutics, volume 22, issue 1, 2014, Pages 1~9
DOI : 10.4062/biomolther.2013.113
Vascular endothelial growth factor (VEGF)-VEGF receptor (VEGFR) system has been shown to play central roles not only in physiological angiogenesis, but also in pathological angiogenesis in diseases such as cancer. Based on these findings, a variety of anti-angiogenic drugs, including anti-VEGF antibodies and VEGFR/multi-receptor kinase inhibitors have been developed and approved for the clinical use. While the clinical efficacy of these drugs has been clearly demonstrated in cancer patients, they have not been shown to be effective in curing cancer, suggesting that further improvement in their design is necessary. Abnormal expression of an endogenous VEGF-inhibitor sFlt-1 has been shown to be involved in a variety of diseases, such as preeclampsia and aged macular degeneration. In addition, various factors modulating angiogenic processes have been recently isolated. Given this complexity then, extensive studies on the interrelationship between VEGF signals and other angiogenesis-regulatory systems will be important for developing future strategies to suppress diseases with an angiogenic component.
Methyl p-Hydroxycinnamate Suppresses Lipopolysaccharide-Induced Inflammatory Responses through Akt Phosphorylation in RAW264.7 Cells
Vo, Van Anh ; Lee, Jae-Won ; Shin, Seung-Yeon ; Kwon, Jae-Hyun ; Lee, Hee Jae ; Kim, Sung-Soo ; Kwon, Yong-Soo ; Chun, Wanjoo ;
Biomolecules & Therapeutics, volume 22, issue 1, 2014, Pages 10~16
DOI : 10.4062/biomolther.2013.095
Derivatives of caffeic acid have been reported to possess diverse pharmacological properties such as anti-inflammatory, anti-tumor, and neuroprotective effects. However, the biological activity of methyl p-hydroxycinnamate, an ester derivative of caffeic acid, has not been clearly demonstrated. This study aimed to elucidate the anti-inflammatory mechanism of methyl p-hydroxycinnamate in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Methyl p-hydroxycinnamate significantly inhibited LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and
and the protein expression of iNOS and COX-2. Methyl p-hydroxycinnamate also suppressed LPS-induced overproduction of pro-inflammatory cytokines such as IL-
. In addition, methyl p-hydroxycinnamate significantly suppressed LPS-induced degradation of
, which retains NF-
in the cytoplasm, consequently inhibiting the transcription of pro-inflammatory genes by NF-
in the nucleus. Methyl p-hydroxycinnamate exhibited significantly increased Akt phosphorylation in a concentration-dependent manner. Furthermore, inhibition of Akt signaling pathway with wortmaninn abolished methyl p-hydroxycinnamate-induced Akt phosphorylation. Taken together, the present study clearly demonstrates that methyl p-hydroxycinnamate exhibits anti-inflammatory activity through the activation of Akt signaling pathway in LPS-stimulated RAW264.7 macrophage cells.
α-Asarone Ameliorates Memory Deficit in Lipopolysaccharide-Treated Mice via Suppression of Pro-Inflammatory Cytokines and Microglial Activation
Shin, Jung-Won ; Cheong, Young-Jin ; Koo, Yong-Mo ; Kim, Sooyong ; Noh, Chung-Ku ; Son, Young-Ha ; Kang, Chulhun ; Sohn, Nak-Won ;
Biomolecules & Therapeutics, volume 22, issue 1, 2014, Pages 17~26
DOI : 10.4062/biomolther.2013.102
-Asarone exhibits a number of pharmacological actions including neuroprotective, anti-oxidative, anticonvulsive, and cognitive enhancing action. The present study investigated the effects of
-asarone on pro-inflammatory cytokines mRNA, microglial activation, and neuronal damage in the hippocampus and on learning and memory deficits in systemic lipopolysaccharide (LPS)-treated C57BL/6 mice. Varying doses of
-asarone was orally administered (7.5, 15, or 30 mg/kg) once a day for 3 days before the LPS (3 mg/kg) injection.
-Asarone significantly reduced TNF-
mRNA at 4 and 24 hours after the LPS injection at dose of 30 mg/kg. At 24 hours after the LPS injection, the loss of CA1 neurons, the increase of TUNEL-labeled cells, and the up-regulation of BACE1 expression in the hippocampus were attenuated by 30 mg/kg of
-Asarone significantly reduced Iba1 protein expression in the hippocampal tissue at a dose of 30 mg/kg.
-Asarone did not reduce the number of Iba1-expressing microglia on immunohistochemistry but the average cell size and percentage areas of Iba1-expressing microglia in the hippocampus were significantly decreased by 30 mg/kg of
-asarone treatment. In the Morris water maze test,
-asarone significantly prolonged the swimming time spent in the target and peri-target zones.
-Asarone also significantly increased the number of target heading and memory score in the Morris water maze. The results suggest that inhibition of pro-inflammatory cytokines and microglial activation in the hippocampus by
-asarone may be one of the mechanisms for the
-asarone-mediated ameliorating effect on memory deficits.
Curcumin Inhibits the Activation of Immunoglobulin E-Mediated Mast Cells and Passive Systemic Anaphylaxis in Mice by Reducing Serum Eicosanoid and Histamine Levels
Li, Xian ; Lu, Yue ; Jin, Ye ; Son, Jong-Keun ; Lee, Seung Ho ; Chang, Hyeun Wook ;
Biomolecules & Therapeutics, volume 22, issue 1, 2014, Pages 27~34
DOI : 10.4062/biomolther.2013.092
Curcumin is naturally occurring polyphenolic compound found in turmeric and has many pharmacological activities. The present study was undertaken to evaluate anti-allergic inflammatory activity of curcumin, and to investigate its inhibitory mechanisms in immunoglobulin E (IgE)/Ag-induced mouse bone marrow-derived mast cells (BMMCs) and in a mouse model of IgE/Ag-mediated passive systemic anaphylaxis (PSA). Curcumin inhibited cyclooxygenase-2 (COX-2) dependent prostaglandin
) and 5-lipoxygenase (5-LO) dependent leukotriene
) generation dose-dependently in BMMCs. To probe the mechanism involved, we assessed the effects of curcumin on the phosphorylation of Syk and its downstream signal molecules. Curcumin inhibited intracellular
influx via phospholipase
) activation and the phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear factor-
) pathway. Furthermore, the oral administration of curcumin significantly attenuated IgE/Ag-induced PSA, as determined by serum
, and histamine levels. Taken together, this study shows that curcumin offers a basis for drug development for the treatment of allergic inflammatory diseases.
Inhibitory Effects of Resveratrol on Melanin Synthesis in Ultraviolet B-Induced Pigmentation in Guinea Pig Skin
Lee, Taek Hwan ; Seo, Jae Ok ; Baek, So-Hyeon ; Kim, Sun Yeou ;
Biomolecules & Therapeutics, volume 22, issue 1, 2014, Pages 35~40
DOI : 10.4062/biomolther.2013.081
Resveratrol is a polyphenolic compound found in various natural products such as grapes and berries and possesses anti-cancer, anti-hyperlipidemia, and anti-aging properties. Recently, it has been reported that resveratrol inhibits
-melanocyte-stimulating hormone signaling, viability, and migration in melanoma cells. However, these effects have not been confirmed in vivo, specifically brownish guinea pigs. To evaluate the potential of resveratrol as a regulator of melanin for hyperpigmentation therapy, the influence of resveratrol on pigmentation was investigated by ultraviolet B-induced hyperpigmentation in brownish guinea pig skin. We found that resveratrol reduced the expression of melanogenesis-related proteins tyrosinase, tyrosinase-related proteins 1 and 2, and microphthalmia-associated transcription factor in melanoma cells. Furthermore, topical application of resveratrol was demonstrated to significantly decrease hyperpigmentation on ultraviolet B-stimulated guinea pig skin in vivo. Based on our histological data, resveratrol inhibits melanin synthesis via a reduction in tyrosinase-related protein 2 among the melanogenic enzymes. This study is the first to provide evidence supporting resveratrol as a depigmentation agent, along with further clinical investigation of resveratrol in ultraviolet B-induced skin disorders such as hyperpigmentation and skin photoaging.
Antiviral Activity of Hederasaponin B from Hedera helix against Enterovirus 71 Subgenotypes C3 and C4a
Song, JaeHyoung ; Yeo, Sang-Gu ; Hong, Eun-Hye ; Lee, Bo-Ra ; Kim, Jin-Won ; Kim, JeongHoon ; Jeong, HyeonGun ; Kwon, YongSoo ; Kim, HyunPyo ; Lee, SangWon ; Park, Jae-Hak ; Ko, Hyun-Jeong ;
Biomolecules & Therapeutics, volume 22, issue 1, 2014, Pages 41~46
DOI : 10.4062/biomolther.2013.108
Enterovirus 71 (EV71) is the predominant cause of hand, foot and mouth disease (HFMD). The antiviral activity of hederasaponin B from Hedera helix against EV71 subgenotypes C3 and C4a was evaluated in vero cells. In the current study, the antiviral activity of hederasaponin B against EV71 C3 and C4a was determined by cytopathic effect (CPE) reduction method and western blot assay. Our results demonstrated that hederasaponin B and 30% ethanol extract of Hedera helix containing hederasaponin B showed significant antiviral activity against EV71 subgenotypes C3 and C4a by reducing the formation of a visible CPE. Hederasaponin B also inhibited the viral VP2 protein expression, suggesting the inhibition of viral capsid protein synthesis.These results suggest that hederasaponin B and Hedera helix extract containing hederasaponin B can be novel drug candidates with broad-spectrum antiviral activity against various subgenotypes of EV71.
Beneficial Antioxidative and Antiperoxidative Effect of Cinnamaldehyde Protect Streptozotocin-Induced Pancreatic β-Cells Damage in Wistar Rats
Subash-Babu, P. ; Alshatwi, Ali A. ; Ignacimuthu, S. ;
Biomolecules & Therapeutics, volume 22, issue 1, 2014, Pages 47~54
DOI : 10.4062/biomolther.2013.100
The present study was aimed to evaluate the antioxidant defense system of cinnamaldehyde in normal, diabetic rats and its possible protection of pancreatic
-cells against its gradual loss under diabetic conditions. In vitro free radical scavenging effect of cinnamaldehyde was determined using DPPH (1,1-diphenyl-2-dipicrylhydrazyl), superoxide radical, and nitric oxide radical. Streptozotocin (STZ) diabetic rats were orally administered with cinnamaldehyde at concentrations of 5, 10 and 20 mg/kg body weight for 45 days. At the end of the experiment, the levels of plasma lipid peroxides and antioxidants such as vitamin C, vitamin E, ceruloplasmin, catalase, superoxide dismutase, reduced glutathione and glutathione peroxidase were determined. A significant increase in the levels of plasma glucose, vitamin E, ceruloplasmin, and lipid peroxides and significant decrease in the levels of plasma insulin and reduced glutathione were observed in the diabetic rats. Also the activities of pancreatic antioxidant enzymes were altered in the STZ-induced diabetic rats. The altered enzyme activities were reverted to near-normal levels after treatment with cinnamaldehyde and glibenclamide. Histopathological studies also revealed a protective effect of cinnamaldehyde on pancreatic
-cells. Cinnamaldehyde enhances the antioxidant defense against reactive oxygen species produced under hyperglycemic conditions and thus protects pancreatic
-cells against their loss and exhibits antidiabetic properties.
Inhibition of TNF-α-Mediated NF-κB Transcriptional Activity by Dammarane-Type Ginsenosides from Steamed Flower Buds of Panax ginseng in HepG2 and SK-Hep1 Cells
Cho, Kyoungwon ; Song, Seok Bean ; Nguyen, Huu Tung ; Kim, Kyoon Eon ; Kim, Young Ho ;
Biomolecules & Therapeutics, volume 22, issue 1, 2014, Pages 55~61
DOI : 10.4062/biomolther.2013.096
Panax ginseng is a medicinal herb that is used worldwide. Its medicinal effects are primarily attributable to ginsenosides located in the root, leaf, seed, and flower. The flower buds of Panax ginseng (FBPG) are rich in various bioactive ginsenosides, which exert immunomodulatory and anti-inflammatory activities. The aim of the present study was to assess the effect of 18 ginsenosides isolated from steamed FBPG on the transcriptional activity of NF-
and the expression of tumor necrosis factor-
)-stimulated target genes in liver-derived cell lines. Noticeably, the ginsenosides
exerted the strongest activity, inhibiting NF-
in a dose-dependent manner. SF and
also showed moderately inhibitory effects. Furthermore, these four compounds inhibited the TNF-
-induced expression of IL8, CXCL1, iNOS, and ICAM1 genes. Consequently, ginsenosides purified from steamed FBPG have therapeutic potential in TNF-
-mediated diseases such as chronic hepatic inflammation.
Inhibition of Proinflammatory Cytokine Generation in Lung Inflammation by the Leaves of Perilla frutescens and Its Constituents
Lim, Hun Jai ; Woo, Kyeong Wan ; Lee, Kang Ro ; Lee, Sang Kook ; Kim, Hyun Pyo ;
Biomolecules & Therapeutics, volume 22, issue 1, 2014, Pages 62~67
DOI : 10.4062/biomolther.2013.088
This study was designed to find some potential natural products and/or constituents inhibiting proinflammatory cytokine generation in lung inflammation, since cytokines such as tumor necrosis factor-
) and interleukin-6 (IL-6) are pivotal for provoking airway inflammation. In our preliminary screening procedure, the 70% ethanol extract of the leaves of Perilla frutescens (PFE) was found to clearly inhibit TNF-
production in the lung at 100 mg/kg, after intranasal lipopolysaccharide treatment of mice. Based on this result, ten constituents including phenylpropanoids (allyltetramethoxybenzene, caffeic acid, dillapiole, elemicin, myristicin, nothoapiole, rosmarinic acid methyl ester, rosmarinic acid) and monoterpenes (perilla aldehyde and perilla ketone) were successfully isolated from the extract. Among them, elemicin and myristicin were found for the first time to concentration-dependently inhibit IL-
-treated IL-6 production from lung alveolar epithelial cells (A549) at concentrations of
. These findings suggest that the phenylpropanoids including elemicin and myristicin have the potential to be new inhibitory agents against lung inflammation and they may contribute, at least in part, to the inhibitory activity of PFE on the lung inflammatory response.
Identification of P-Glycoprotein and Transport Mechanism of Paclitaxel in Syncytiotrophoblast Cells
Lee, Na-Young ; Lee, Ha-Eun ; Kang, Young-Sook ;
Biomolecules & Therapeutics, volume 22, issue 1, 2014, Pages 68~72
DOI : 10.4062/biomolther.2013.105
When chemotherapy is administered during pregnancy, it is important to consider the fetus chemotherapy exposure, because it may lead to fetal consequences. Paclitaxel has become widely used in the metastatic and adjuvant settings for woman with cancer including breast and ovarian cancer. Therefore, we attempted to clarify the transport mechanisms of paclitaxel through blood-placenta barrier using rat conditionally immortalized syncytiotrophoblast cell lines (TR-TBTs). The uptake of paclitaxel was time- and temperature-dependent. Paclitaxel was eliminated about 50% from the cells within 30 min. The uptake of paclitaxel was saturable with
in TR-TBT 18d-1 and TR-TBT 18d-2, respectively. [
]Paclitaxel uptake was markedly inhibited by cyclosporine and verapamil, well-known substrates of P-glycoprotein (P-gp) transporter. However, several MRP substrates and organic anions had no effect on [
]paclitaxel uptake in TR-TBT cells. These results suggest that P-gp may be involved in paclitaxel transport at the placenta. TR-TBT cells expressed mRNA of P-gp. These findings are important for therapy of breast and ovarian cancer of pregnant women, and should be useful data in elucidating teratogenicity of paclitaxel during pregnancy.
Enhanced In Vitro Skin Deposition Properties of Retinyl Palmitate through Its Stabilization by Pectin
Suh, Dong-Churl ; Kim, Yeongseok ; Kim, Hyeongmin ; Ro, Jieun ; Cho, Seong-Wan ; Yun, Gyiae ; Choi, Sung-Up ; Lee, Jaehwi ;
Biomolecules & Therapeutics, volume 22, issue 1, 2014, Pages 73~77
DOI : 10.4062/biomolther.2013.094
The purpose of this study was to examine the effect of stabilization of retinyl palmitate (RP) on its skin permeation and distribution profiles. Skin permeation and distribution study were performed using Franz diffusion cells along with rat dorsal skin, and the effect of drug concentration and the addition of pectin on skin deposition profiles of RP was observed. The skin distribution of RP increased in a concentration dependent manner and the formulations containing 0.5 and 1 mg of pectin demonstrated significantly increased RP distributions in the epidermis. Furthermore, it was found that skin distribution of RP could be further improved by combined use of pectin and ascorbyl palmitate (AP), due largely to their anti-oxidative effect. These results clearly demonstrate that the skin deposition properties of RP can be improved by stabilizing RP with pectin. Therefore, it is strongly suggested that pectin could be used in the pharmaceutical and cosmetic formulations as an efficient stabilizing agent and as skin penetration modulator.
Formulation and Evaluation of Irinotecan Suppository for Rectal Administration
Feng, Haiyang ; Zhu, Yuping ; Li, Dechuan ;
Biomolecules & Therapeutics, volume 22, issue 1, 2014, Pages 78~81
DOI : 10.4062/biomolther.2013.087
Irinotecan suppository was prepared using the moulding method with a homogeneous blend. A sensitive and specific fluorescence method was developed and validated for the determination of irinotecan in plasma using HPLC. The pharmacokinetics of intravenous administered and rectal administered in rabbits was investigated. Following a single intravenous dose of irinotecan (50 mg/kg), the plasma irinotecan concentration demonstrated a bi-exponential decay, with a rapid decline over 15 min.
, respectively. Following rectal administration of 100 mg/kg irinotecan, the plasma irinotecan concentration reached a peak of
at 4 h. The
, respectively. It representing ~50.6% of the absolute bioavailability.