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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Biomolecules and Therapeutics
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Journal DOI :
The Korean Society of Applied Pharmacology
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Volume & Issues
Volume 24, Issue 4 - Jul 2016
Volume 24, Issue 3 - May 2016
Volume 24, Issue 2 - Mar 2016
Volume 24, Issue 1 - Jan 2016
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Alpha-Ketoglutarate: Physiological Functions and Applications
Wu, Nan ; Yang, Mingyao ; Gaur, Uma ; Xu, Huailiang ; Yao, Yongfang ; Li, Diyan ;
Biomolecules and Therapeutics, volume 24, issue 1, 2016, Pages 1~8
DOI : 10.4062/biomolther.2015.078
Alpha-ketoglutarate (AKG) is a key molecule in the Krebs cycle determining the overall rate of the citric acid cycle of the organism. It is a nitrogen scavenger and a source of glutamate and glutamine that stimulates protein synthesis and inhibits protein degradation in muscles. AKG as a precursor of glutamate and glutamine is a central metabolic fuel for cells of the gastrointestinal tract as well. AKG can decrease protein catabolism and increase protein synthesis to enhance bone tissue formation in the skeletal muscles and can be used in clinical applications. In addition to these health benefits, a recent study has shown that AKG can extend the lifespan of adult Caenorhabditis elegans by inhibiting ATP synthase and TOR. AKG not only extends lifespan, but also delays age-related disease. In this review, we will summarize the advances in AKG research field, in the content of its physiological functions and applications.
NDRG2 Expression Decreases Tumor-Induced Osteoclast Differentiation by Down-regulating ICAM1 in Breast Cancer Cells
Kim, Bomi ; Nam, Sorim ; Lim, Ji Hyun ; Lim, Jong-Seok ;
Biomolecules and Therapeutics, volume 24, issue 1, 2016, Pages 9~18
DOI : 10.4062/biomolther.2015.105
Bone matrix is properly maintained by osteoclasts and osteoblasts. In the tumor microenvironment, osteoclasts are increasingly differentiated by the various ligands and cytokines secreted from the metastasized cancer cells at the bone metastasis niche. The activated osteoclasts generate osteolytic lesions. For this reason, studies focusing on the differentiation of osteoclasts are important to reduce bone destruction by tumor metastasis. The N-myc downstream-regulated gene 2 (NDRG2) has been known to contribute to the suppression of tumor growth and metastasis, but the precise role of NDRG2 in osteoclast differentiation induced by cancer cells has not been elucidated. In this study, we demonstrate that NDRG2 expression in breast cancer cells has an inhibitory effect on osteoclast differentiation. RAW 264.7 cells, which are monocytic preosteoclast cells, treated with the conditioned media (CM) of murine breast cancer cells (4T1) expressing NDRG2 are less differentiated into the multinucleated osteoclast-like cells than those treated with the CM of 4T1-WT or 4T1-mock cells. Interestingly, 4T1 cells stably expressing NDRG2 showed a decreased mRNA and protein level of intercellular adhesion molecule 1 (ICAM1), which is known to enhance osteoclast maturation. Osteoclast differentiation was also reduced by ICAM1 knockdown in 4T1 cells. In addition, blocking the interaction between soluble ICAM1 and ICAM1 receptors significantly decreased osteoclastogenesis of RAW 264.7 cells in the tumor environment. Collectively, these results suggest that the reduction of ICAM1 expression by NDRG2 in breast cancer cells decreases osteoclast differentiation, and demonstrate that excessive bone resorption could be inhibited via ICAM1 down-regulation by NDRG2 expression.
Long Noncoding RNA MHRT Protects Cardiomyocytes against H
Zhang, Jianying ; Gao, Caihua ; Meng, Meijuan ; Tang, Hongxia ;
Biomolecules and Therapeutics, volume 24, issue 1, 2016, Pages 19~24
DOI : 10.4062/biomolther.2015.066
Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. The exploration of new biomarkers with high sensitivity and specificity for early diagnosis of AMI therefore becomes one of the primary task. In the current study, we aim to detect whether there is any heart specific long noncoding RNA (lncRNA) releasing into the circulation during AMI, and explore its function in the neonatal rat cardiac myocytes injury induced by
. Our results revealed that the cardiac-specific lncRNA MHRT (Myosin Heavy Chain Associated RNA Transcripts) was significantly elevated in the blood from AMI patients compared with the healthy control (
). Using an in vitro neonatal rat cardiac myocytes injury model, we demonstrated that lncRNA MHRT was upregulated in the cardiac myocytes after treatment with hydrogen peroxide (
) via real-time RT-PCR (qRT-PCR). Furthermore, we knockdowned the MHRT gene by siRNA to confirm its roles in the
-induced cardiac cell apoptosis, and found that knockdown of MHRT led to significant more apoptotic cells than the non-target control (
), indicating that the lncRNA MHRT is a protective factor for cardiomyocyte and the plasma concentration of MHRT may serve as a biomarker for myocardial infarction diagnosis in humans AMI.
Lobaric Acid Inhibits VCAM-1 Expression in TNF-α-Stimulated Vascular Smooth Muscle Cells via Modulation of NF-κB and MAPK Signaling Pathways
Kwon, Ii-Seul ; Yim, Joung-Han ; Lee, Hong-Kum ; Pyo, Suhkneung ;
Biomolecules and Therapeutics, volume 24, issue 1, 2016, Pages 25~32
DOI : 10.4062/biomolther.2015.084
Lichens have been known to possess multiple biological activities, including anti-proliferative and anti-inflammatory activities. Vascular cell adhesion molecule-1 (VCAM-1) may play a role in the development of atherosclerosis. Hence, VCAM-1 is a possible therapeutic target in the treatment of the inflammatory disease. However, the effect of lobaric acid on VCAM-1 has not yet been investigated and characterized. For this study, we examined the effect of lobaric acid on the inhibition of VCAM-1 in tumor necrosis factor-alpha (TNF-
)-stimulated mouse vascular smooth muscle cells. Western blot and ELISA showed that the increased expression of VCAM-1 by TNF-
was significantly suppressed by the pre-treatment of lobaric acid (
) for 2 h. Lobaric acid abrogated TNF-
activity through preventing the degradation of
and phosphorylation of extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK), and p38 mitogen activated protein (MAP) kinase. Lobaric acid also inhibited the expression of TNF-
receptor 1 (TNF-R1). Overall, our results suggest that lobaric acid inhibited VCAM-1 expression through the inhibition of p38, ERK, JNK and NF-
signaling pathways, and downregulation of TNF-R1 expression. Therefore, it is implicated that lobaric acid may suppress inflammation by altering the physiology of the atherosclerotic lesion.
Protopanaxatriol Ginsenoside Rh1 Upregulates Phase II Antioxidant Enzyme Gene Expression in Rat Primary Astrocytes: Involvement of MAP Kinases and Nrf2/ARE Signaling
Jung, Ji-Sun ; Lee, Sang-Yoon ; Kim, Dong-Hyun ; Kim, Hee-Sun ;
Biomolecules and Therapeutics, volume 24, issue 1, 2016, Pages 33~39
DOI : 10.4062/biomolther.2015.129
Oxidative stress activates several intracellular signaling cascades that may have deleterious effects on neuronal cell survival. Thus, controlling oxidative stress has been suggested as an important strategy for prevention and/or treatment of neurodegenerative diseases. In this study, we found that ginsenoside Rh1 inhibited hydrogen peroxide-induced reactive oxygen species generation and subsequent cell death in rat primary astrocytes. Rh1 increased the expression of phase II antioxidant enzymes, such as heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1, superoxide dismutase-2, and catalase, that are under the control of Nrf2/ARE signaling pathways. Further mechanistic studies showed that Rh1 increased the nuclear translocation and DNA binding of Nrf2 and c-Jun to the antioxidant response element (ARE), and increased the ARE-mediated transcription activities in rat primary astrocytes. Analysis of signaling pathways revealed that MAP kinases are important in HO-1 expression, and act by modulating ARE-mediated transcriptional activity. Therefore, the upregulation of antioxidant enzymes by Rh1 may provide preventive therapeutic potential for various neurodegenerative diseases that are associated with oxidative stress.
PXR Mediated Protection against Liver Inflammation by Ginkgolide A in Tetrachloromethane Treated Mice
Ye, Nanhui ; Wang, Hang ; Hong, Jing ; Zhang, Tao ; Lin, Chaotong ; Meng, Chun ;
Biomolecules and Therapeutics, volume 24, issue 1, 2016, Pages 40~48
DOI : 10.4062/biomolther.2015.077
The pregnane X receptor (PXR), a liver and intestine specific receptor,, has been reported to be related with the repression of inflammation as well as activation of cytochromosome P450 3A (CYP3A) expression. We examined the effect of PXR on tetrachloromethane (CCl4)-induced mouse liver inflammation in this work. Ginkgolide A, one main component of Ginkgo biloba extracts (GBE), activated PXR and enhanced PXR expression level, displayed both significant therapeutic effect and preventive effect against
-induced mouse hepatitis. siRNA-mediated decrease of PXR expression significantly reduced the efficacy of Ginkgolide A in treating
-induced inflammation in mice. Flavonoids, another important components of GBE, were shown anti-inflammatory effect in a different way from Ginkgolide A which might be independent on PXR because flavonoids significantly inhibited CYP3A11 activities in mice. The results indicated that anti-inflammatory effect of PXR might be mediated by enhancing transcription level of
through binding of
. Inhibition of NF-
activity by NF-
is one of the potential mechanisms of Ginkgolide A against CCl4-induced liver inflammation.
Aloe-Emodin Protects RIN-5F (Pancreatic β-cell) Cell from Glucotoxicity via Regulation of Pro-Inflammatory Cytokine and Downregulation of Bax and Caspase 3
Alshatwi, Ali A ; Subash-Babu, P. ;
Biomolecules and Therapeutics, volume 24, issue 1, 2016, Pages 49~56
DOI : 10.4062/biomolther.2015.056
To determine the protective effect of aloe-emodin (AE) from high glucose induced toxicity in RIN-5F (pancreatic
-cell) cell and restoration of its function was analyzed. RIN-5F cells have been cultured in high glucose (25 mM glucose) condition, with and without AE treatment. RIN-5F cells cultured in high glucose decreased cell viability and increased ROS levels after 48 hr compared with standard medium (5.5 mM glucose). Glucotoxicity was confirmed by significantly increased ROS production, increased pro-inflammatory (IFN-
,) & decreased anti-inflammatory (IL-6&IL-10) cytokine levels, increased DNA fragmentation. In addition, we found increased Bax, caspase 3, Fadd, and Fas and significantly reduced Bcl-2 expression after 48 hr. RIN-5F treated with both high glucose and AE (
) decreased ROS generation and prevent RIN-5F cell from glucotoxicity. In addition, AE treated cells cultured in high glucose were transferred to standard medium, normal responsiveness to glucose was restored within 8hr and normal basal insulin release within 24 hr was achieved when compared to high glucose.
Endothelium-Independent Effect of Fisetin on the Agonist-Induced Regulation of Vascular Contractility
Je, Hyun Dong ; Sohn, Uy Dong ; La, Hyen-Oh ;
Biomolecules and Therapeutics, volume 24, issue 1, 2016, Pages 57~61
DOI : 10.4062/biomolther.2015.104
Fisetin, a natural flavonoid found in a variety of vegetables and fruits, has been shown to possess many biological functions. The present study was undertaken to investigate the influence of fisetin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Fisetin significantly relaxed fluoride-, thromboxane
- or phorbol ester-induced vascular contraction suggesting as a possible anti-hypertensive on the agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, fisetin significantly inhibited fluoride-induced increases in pMYPT1 levels and phorbol ester-induced increases in pERK1/2 levels suggesting the mechanism involving the inhibition of Rho-kinase activity and the subsequent phosphorylation of MYPT1 and MEK activity and the subsequent phosphorylation of ERK1/2. This study provides evidence regarding the mechanism underlying the relaxation effect of fisetin on agonist-induced vascular contraction regardless of endothelial function.
Amygdalin Regulates Apoptosis and Adhesion in Hs578T Triple-Negative Breast Cancer Cells
Lee, Hye Min ; Moon, Aree ;
Biomolecules and Therapeutics, volume 24, issue 1, 2016, Pages 62~66
DOI : 10.4062/biomolther.2015.172
-glucoside, belongs to aromatic cyanogenic glycoside group derived from rosaceous plant seed. Mounting evidence has supported the anti-cancer effects of amygdalin. However, whether amygdalin indeed acts as an anti-tumor agent against breast cancer cells is not clear. The present study aimed to investigate the effect of amygdalin on the proliferation of human breast cancer cells. Here, we show that amygdalin exerted cytotoxic activities on estrogen receptors (ER)-positive MCF7 cells, and MDA-MB-231 and Hs578T triple-negative breast cancer (TNBC) cells. Amygdalin induced apoptosis of Hs578T TNBC cells. Amygdalin downregulated B-cell lymphoma 2 (Bcl-2), upregulated Bcl-2-associated X protein (Bax), activated of caspase-3 and cleaved poly ADP-ribose polymerase (PARP). Amygdalin activated a pro-apoptotic signaling molecule p38 mitogen-activated protein kinases (p38 MAPK) in Hs578T cells. Treatment of amygdalin significantly inhibited the adhesion of Hs578T cells, in which integrin
may be involved. Taken together, this study demonstrates that amygdalin induces apoptosis and inhibits adhesion of breast cancer cells. The results suggest a potential application of amygdalin as a chemopreventive agent to prevent or alleviate progression of breast cancer, especially TNBC.
Inhibition of Lung Inflammation by Acanthopanax divaricatus var. Albeofructus and Its Constituents
Lee, Ju Hee ; Sun, Ya Nan ; Kim, Young Ho ; Lee, Sang Kook ; Kim, Hyun Pyo ;
Biomolecules and Therapeutics, volume 24, issue 1, 2016, Pages 67~74
DOI : 10.4062/biomolther.2015.070
In order to find potential therapeutic agents on lung inflammatory conditions, the extracts of Acanthopanax divaricatus var. albeofructus were prepared and its constituents were isolated. They include lignans such as (+)-syringaresinol (1), acanthoside B (2), salvadoraside (3) and acanthoside D (4), lariciresinol-9-O-
-D-glucopyranoside (5) and phenylpropanoids such as 4-[(1E)-3-methoxy-1-propenyl]phenol (6), coniferin (7), and methyl caffeate (8). The extracts and several constituents such as compound 1, 6 and 8 inhibited the production of inflammatory markers, IL-6 and nitric oxide, from IL-
-treated lung epithelial cells and lipopolysaccharide (LPS)-treated alveolar macrophages. Furthermore, the extracts and compound 4 significantly inhibited lung inflammation in lipolysaccharide-treated acute lung injury in mice by oral administration. Thus it is suggested that A. divaricatus var. albeofructus and its several constituents may be effective against lung inflammation.
Rosmarinic Acid Attenuates Cell Damage against UVB Radiation-Induced Oxidative Stress via Enhancing Antioxidant Effects in Human HaCaT Cells
Fernando, Pattage Madushan Dilhara Jayatissa ; Piao, Mei Jing ; Kang, Kyoung Ah ; Ryu, Yea Seong ; Hewage, Susara Ruwan Kumara Madduma ; Chae, Sung Wook ; Hyun, Jin Won ;
Biomolecules and Therapeutics, volume 24, issue 1, 2016, Pages 75~84
DOI : 10.4062/biomolther.2015.069
This study was designed to investigate the cytoprotective effect of rosmarinic acid (RA) on ultraviolet B (UVB)-induced oxidative stress in HaCaT keratinocytes. RA exerted a significant cytoprotective effect by scavenging intracellular ROS induced by UVB. RA also attenuated UVB-induced oxidative macromolecular damage, including protein carbonyl content, DNA strand breaks, and the level of 8-isoprostane. Furthermore, RA increased the expression and activity of superoxide dismutase, catalase, heme oxygenase-1, and their transcription factor Nrf2, which are decreased by UVB radiation. Collectively, these data indicate that RA can provide substantial cytoprotection against the adverse effects of UVB radiation by modulating cellular antioxidant systems, and has potential to be developed as a medical agent for ROS-induced skin diseases.
Anti-Melanogenic Potentials of Nanoparticles from Calli of Resveratrol-Enriched Rice against UVB-Induced Hyperpigmentation in Guinea Pig Skin
Lee, Taek Hwan ; Kang, Ji Hee ; Seo, Jae Ok ; Baek, So-Hyeon ; Moh, Sang Hyun ; Chae, Jae Kyoung ; Park, Yong Un ; Ko, Young Tag ; Kim, Sun Yeou ;
Biomolecules and Therapeutics, volume 24, issue 1, 2016, Pages 85~93
DOI : 10.4062/biomolther.2015.165
We already reported that genetically engineered resveratrol-enriched rice (RR) showed to down-regulate skin melanogenesis. To be developed to increase the bioactivity of RR using calli from plants, RR was adopted for mass production using plant tissue culture technologies. In addition, high-pressure homogenization (HPH) was used to increase the biocompatibility and penetration of the calli from RR into the skin. We aimed to develop anti-melanogenic agents incorporating calli of RR (cRR) and nanoparticles by high-pressure homogenization, examining the synergistic effects on the inhibition of UVB-induced hyperpigmentation. Depigmentation was observed following topical application of micro-cRR, nano-calli of normal rice (cNR), and nano-cRR to ultraviolet B (UVB)-stimulated hyperpigmented guinea pig dorsal skin. Colorimetric analysis, tyrosinase immunostaining, and Fontana-Masson staining for UVB-promoted melanin were performed. Nano-cRR inhibited changes in the melanin color index caused by UVB-promoted hyperpigmentation, and demonstrated stronger anti-melanogenic potential than micro-cRR. In epidermal skin, nano-cRR repressed UVB-promoted melanin granules, thereby suppressing hyperpigmentation. The UVB-enhanced, highly expressed tyrosinase in the basal layer of the epidermis was inhibited by nano-cRR more prominently than by micro-cRR and nano-cNR. The anti-melanogenic potency of nano-cRR also depended on pH and particle size. Nano-cRR shows promising potential to regulate skin pigmentation following UVB exposure.
Effects of Bisphosphonates on Glucose Transport in a Conditionally Immortalized Rat Retinal Capillary Endothelial Cell Line (TR-iBRB Cells)
Lee, Na-Young ; Park, Hyun-Joo ; Kang, Young-Sook ;
Biomolecules and Therapeutics, volume 24, issue 1, 2016, Pages 94~98
DOI : 10.4062/biomolther.2015.183
The objective of the present study was to elucidate the effect of bisphosphonates, anti-osteoporosis agents, on glucose uptake in retinal capillary endothelial cells under normal and high glucose conditions. The change of glucose uptake by pre-treatment of bisphosphonates at the inner blood-retinal barrier (iBRB) was determined by measuring cellular uptake of
-O-methyl glucose (3-OMG) using a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB cells) under normal and high glucose conditions.
-OMG uptake was inhibited by simultaneous treatment of unlabeled D-glucose and 3-OMG as well as glucose transport inhibitor, cytochalasin B. On the other hand, simultaneous treatment of alendronate or pamidronate had no significant inhibitory effect on
-OMG uptake by TR-iBRB cells. Under high glucose condition of TR-iBRB cells,
-OMG uptake was increased at 48 h. However,
-OMG uptake was decreased significantly by pre-treatment of alendronate or pamidronate compared with the values for normal and high glucose conditions. Moreover, geranylgeraniol (GGOH), a mevalonate pathway intermediate, increased the uptake of
-OMG reduced by bisphosphonates pre-treatment. But, pre-treatment of histamine did not show significant inhibition of
-OMG uptake. The glucose uptake may be down regulated by inhibiting the mevalonate pathway with pre-treatment of bisphosphonates in TR-iBRB cells at high glucose condition.
Effects of Triclosan on Neural Stem Cell Viability and Survival
Park, Bo Kyung ; Gonzales, Edson Luck T. ; Yang, Sung Min ; Bang, Minji ; Choi, Chang Soon ; Shin, Chan Young ;
Biomolecules and Therapeutics, volume 24, issue 1, 2016, Pages 99~107
DOI : 10.4062/biomolther.2015.164
Triclosan is an antimicrobial or sanitizing agent used in personal care and household products such as toothpaste, soaps, mouthwashes and kitchen utensils. There are increasing evidence of the potentially harmful effects of triclosan in many systemic and cellular processes of the body. In this study, we investigated the effects of triclosan in the survivability of cultured rat neural stem cells (NSCs). Cortical cells from embryonic day 14 rat embryos were isolated and cultured in vitro. After stabilizing the culture, triclosan was introduced to the cells with concentrations ranging from
and in varied time periods. Thereafter, cell viability parameters were measured using MTT assay and PI staining. TCS decreased the cell viability of treated NSC in a concentration-dependent manner along with increased expressions of apoptotic markers, cleaved caspase-3 and Bax, while reduced expression of Bcl2. To explore the mechanisms underlying the effects of TCS in NSC, we measured the activation of MAPKs and intracellular ROS. TCS at
induced the activations of both p38 and JNK, which may adversely affect cell survival. In contrast, the activities of ERK, Akt and PI3K, which are positively correlated with cell survival, were inhibited. Moreover, TCS at this concentration augmented the ROS generation in treated NSC and depleted the glutathione activity. Taken together, these results suggest that TCS can induce neurodegenerative effects in developing rat brains through mechanisms involving ROS activation and apoptosis initiation.