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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
> Journal Vol & Issue
Biomolecules and Therapeutics
Journal Basic Information
Journal DOI :
The Korean Society of Applied Pharmacology
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Volume & Issues
Volume 17, Issue 4 - Oct 2009
Volume 17, Issue 3 - Jul 2009
Volume 17, Issue 2 - Apr 2009
Volume 17, Issue 1 - Jan 2009
Selecting the target year
NF-κB and Therapeutic Approach
Lee, Chang-Hoon ; Kim, Soo-Youl ;
Biomolecules and Therapeutics, volume 17, issue 3, 2009, Pages 219~240
DOI : 10.4062/biomolther.2009.17.3.219
has been identified as a transcription factor associated with immune cell activation, groups of researchers have dedicated to reveal detailed mechanisms of nuclear factor of
) in inflammatory signaling for decades. The various molecular components of NF-
transcription factor pathway have been being evaluated as important therapeutic targets due to their roles in diverse human diseases including inflammation, cystic fibrosis, sepsis, rheumatoid arthritis, cancer, atherosclerosis, ischemic injury, myocardial infarction, osteoporosis, transplantation rejection, and neurodegeneration. With regards to new drugs directly or indirectly modulating the NF-
pathway, FDA recently approved a proteasome inhibitor bortezomib for the treatment of multiple myeloma. Many pharmaceutical companies have been trying to develop new drugs to inhibit various kinases in the NF-
signaling pathway for many therapeutic applications. However, a gene knock-out study for
in the NF-
pathway has given rise to controversies associated with efficacy as therapeutics. Mice lacking hepatocyte
accelerated cancer instead of preventing progress of cancer. However, it is clear that pharmacological inhibition of
appears to be beneficial to reduce HCC. This article will update issues of the NF-
pathway and inhibitors regulating this pathway.
The Effect of Methylsulfonylmethane on Hair Growth Promotion of Magnesium Ascorbyl Phosphate for the Treatment of Alopecia
Shanmugam, Srinivasan ; Baskaran, Rengarajan ; Nagayya-Sriraman, Santhoshkumar ; Yong, Chul-Soon ; Choi, Han-Gon ; Woo, Jong-Soo ; Yoo, Bong-Kyu ;
Biomolecules and Therapeutics, volume 17, issue 3, 2009, Pages 241~248
DOI : 10.4062/biomolther.2009.17.3.241
The purpose of this study was to evaluate the effect of methylsulfonylmethane (MSM) on hair growth promotion of magnesium ascorbyl phosphate (MAP) for the treatment of alopecia. Aqueous solutions of MAP 7.5% with or without MSM 1%, 5% or 10% were prepared and applied onto the depilated back skin of the male mice once a day for 20 days. The degree of hair growth was evaluated by visual scoring using hair growth quantification scale (0-5, 0 being initial state and 5 being complete hair growth). In vitro transdermal penetration and intradermal retention studies of MAP were performed with Franz diffusion cell using hairless mice skin. Hair growth in the group treated with the aqueous solution containing MAP 7.5% and MSM 10% was comparable to or better than the result in the group treated with minoxidil 5% solution. Hair growth promotion of MAP was dose-dependently increased by the presence of MSM used in combination with MAP 7.5% solution. The in vitro transdermal penetration of the MAP was decreased in proportion to the concentration of MSM. However, intradermal retention of MAP was profoundly and dose-proportionally increased as a function of MSM concentration, reaching 802
in the presence of MSM 10% (200-fold increase). The effect of MSM on hair growth promotion of MAP was dose-proportional to the concentration of MSM due to the enhanced intradermal retention of MAP in the presence of MSM. Therefore, topical application of MAP together with MSM appears to be useful for the treatment of alopecia.
Forsythiaside, a Constituent of the Fruits of Forsythia suspense, Ameliorates Scopolamine-Induced Memory Impairment in Mice
Kim, Sun-Ho ; Kim, Dong-Hyun ; Choi, Ji-Joung ; Lee, Jong-Gu ; Lee, Choong-Ho ; Park, Se-Jin ; Jung, Won-Yong ; Park, Dong-Hyun ; Ko, Kwang-Ho ; Lee, Seung-Ho ; Ryu, Jong-Hoon ;
Biomolecules and Therapeutics, volume 17, issue 3, 2009, Pages 249~255
DOI : 10.4062/biomolther.2009.17.3.249
Forsythiaside is a polyphenolic constituent of the fruits of Forsythia suspense Vahl which are widely used as anti-inflammatory herbal raw materials in traditional Chinese medicine. In the present study, the authors assessed the effects of forsythiaside on learning and memory impairments induced by scopolamine using a passive avoidance and the Morris water maze tests in mice. Drug-induced amnesia was induced by scopolamine treatment (1 mg/kg, i.p.). Forsythiaside (10 mg/kg, p.o) administration significantly prevented scopolamine-induced step-through latency reduction in the passive avoidance test and scopolamine-induced increased escape latency in the Morris water maze test (p<0.05). Moreover, in an ex-vivo study, forsythiaside treatment (10 mg/kg, p.o) significantly reduced the increase of thiobarbituric acid reactive substance levels induced by scopolamine (p<0.05). Taken together, the present study suggests that forsythiaside could be useful for the treatment of cognitive impairment, and that its beneficial effects are mediated, in part, by its antioxidative properties.
Hypoglycemic Effect of Yacon Tuber Extract and Its Constituent, Chlorogenic Acid, in Streptozotocin-Induced Diabetic Rats
Park, Jeong-Sook ; Yang, Jae-Sik ; Hwang, Bang-Yeon ; Yoo, Bong-Kyu ; Han, Kun ;
Biomolecules and Therapeutics, volume 17, issue 3, 2009, Pages 256~262
DOI : 10.4062/biomolther.2009.17.3.256
Smallanthus sonchifolius (Yacon, Asteraceae) was originally cultivated in South America and used in food and traditional medicine by Andean inhabitants. Yacon is potentially beneficial for the management of diabetes and is composed of fructooligosaccharides, proteins, minerals and phenolic compounds. The aim of this study was to investigate the hypoglycemic effect of Yacon tuber extract (YTE) and its constituent, chlorogenic acid (CGA), in streptozotocin (STZ)-induced diabetic rats. In this study, a HPLC method was developed for simultaneous determination of major active phenolic components, CGA and caffeic acid in YTE. We investigated the hypoglycemic effect of YTE and CGA in STZ-induced diabetic rats and studied glucose tolerance test (GTT). The effect of orally administered multiple doses of YTE and CGA on plasma biochemical parameters was examined using diabetic rats. We also measured free radical scavenging activity by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Oral administration of YTE (200 mg/kg) and CGA (10 mg/kg) for 6 weeks produced a significant hypoglycemic effect in STZ-induced diabetic rats. YTE and CGA-treated groups exhibited significantly decreased plasma glucose surge during the GTT. Total cholesterol (TC) and triglyceride (TG) concentrations were significantly decreased by 33% and 49%, respectively, in YTE-treated rats. TC and TG concentrations were also significantly decreased by 26 % and 41%, respectively, in CGA-treated rats. In the DPPH assay, free radical scavenging activity of CGA was similar to that of vitamin E, a positive control. This study suggests that YTE and its constituent, CGA, may be a useful option for management of hyperglycemia and diabetic nephropathy.
Evaluation on Pharmacological Activities of 2,4-Dihydroxybenzaldehyde
Jung, Hyun-Joo ; Song, Yun-Seon ; Lim, Chang-Jin ; Park, Eun-Hee ;
Biomolecules and Therapeutics, volume 17, issue 3, 2009, Pages 263~269
DOI : 10.4062/biomolther.2009.17.3.263
4-Hydroxybenzaldehyde, a phenolic compound found in a variety of natural sources, was previously shown to contain anti-inflammatory and related anti-angiogenic and anti-nociceptive activities. The present work was designed to assess some pharmacological activities of 2,4-dihydroxybenzaldehyde (DHD), an analogue of 4-hydroxybenzaldehyde. DHD exhibited a significant inhibition in the chick chorioallantoic membrane (CAM) angiogenesis, and its
. DHD also contained in vivo anti-inflammatory activity using acetic acid-induced permeability and carrageenan-induced air pouch models in mice. In the air pouch model, DHD showed significant suppression in exudate volume, number of polymorphonuclear leukocytes and nitrite content. DHD showed an anti-nociceptive activity in the acetic acid-induced writhing test in mice. It also suppressed enhanced production of nitric oxide (NO) and elevated expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. It was able to slightly decrease the level of reactive oxygen species in the stimulated macrophages. DHD at the used concentrations couldn't modulate the viabilities of RAW264.7 cells. Taken together, like 4-hydroxybenzaldehyde, DHD contains anti-angiogenic, anti-inflammatory and anti-nociceptive activities.
Attenuated Cerebral Ischemic Injury by Polyethylene Glycol-Conjugated Hemoglobin
Cho, Geum-Sil ; Choi, In-Young ; Choi, Yoo-Keum ; Kim, Seul-Ki ; Cai, Ying ; Nho, Kwang ; Lee, Jae-Chul ;
Biomolecules and Therapeutics, volume 17, issue 3, 2009, Pages 270~275
DOI : 10.4062/biomolther.2009.17.3.270
Polyethylene glycol-conjugated hemoglobin (PEG-Hb) has been proposed as a blood substitute for transfusion due to their plasma expansion and oxygen transport capabilities. The protective effect of PEG-Hb on cerebral hypoxic-ischemic injury was investigated in neonatal hypoxia model and adult rat focal cerebral ischemia model. As intravenously administered 30 min before the onset of hypoxia, PEG-Hb markedly protected cerebral hypoxic injury in a neonatal rat hypoxia model. A similar treatment of PEG-Hb largely reduced the ischemic injury ensuing after 2-h middle cerebral artery occlusion followed by 22-h reperfusion. Consistently, neurological disorder was significantly improved by PEG-Hb. The results indicate that the pharmacological blockade of cerebral ischemic injury by using PEG-Hb may provide a useful strategy for the treatment of cerebral stroke.
Extracelluar Signal-Regulated Kinase-Dependent Nitric Oxide Production from Macrophage-Like Cells by Lactic Acid Bacteria
Byeon, Se-Eun ; Yoo, Dae-Sung ; Lee, Jae-Hwi ; Kim, Suk ; Rhee, Man-Hee ; Park, Hwa-Jin ; Cho, Jae-Youl ;
Biomolecules and Therapeutics, volume 17, issue 3, 2009, Pages 276~281
DOI : 10.4062/biomolther.2009.17.3.276
Lactic acid bacteria (LAB) are considered as probiotics with immunostimulatory property. In this study, we investigated the molecular mechanism of its immunostimulating potency on macrophages using combined preparation of LAB (cpLAB). cpLAB is able to strongly stimulate nitric oxide (NO) production as well as inducible NO synthase (iNOS) expression from macrophage-like RAW264.7 cells. The cpLAB-induced NO release seemed to be mediated by extracellular signal-regulated kinase (ERK) but not p38 and C-Jun N-terminal kinase (JNK), since U0126, an ERK inhibitor, clearly suppressed NO production. cpLAB significantly diminished the binding of toll like receptor (TLR)-2 antibody up to 25%, implying that cpLAB-mediated activation of macrophages may be required for the functional activation of TLR-2, but not TLR-4. Therefore, our data suggest that cpLAB may directly allow macrophages to immunostimulating potency via activation of TLR-2 and ERK.
Ochnaflavone, a Natural Biflavonoid, Induces Cell Cycle Arrest and Apoptosis in HCT-15 Human Colon Cancer Cells
Kang, You-Jin ; Min, Hye-Young ; Hong, Ji-Young ; Kim, Yeong-Shik ; Kang, Sam-Sik ; Lee, Sang-Kook ;
Biomolecules and Therapeutics, volume 17, issue 3, 2009, Pages 282~287
DOI : 10.4062/biomolther.2009.17.3.282
Ochnaflavone is a natural biflavonoid and mainly found in the caulis of Lonicera japonica (Caprifoliaceae). Biological activities such as anti-inflammatory and anti-atherogenic effects have been previously reported. The anticancer activity of ochnaflavone, however, has been poorly elucidated yet. In the present study, we investigated the effect of ochnaflavone on the growth inhibitory activity in cultured human colon cancer cell line HCT-15. Ochnaflavone inhibited the proliferation of the cancer cells with an
. Flow cytometric analysis showed that ochnaflavone arrested cell cycle progression in the G2/M phase, and induced the increase of sub-G1 peak in a concentration-dependent manner. Induction of cell cycle arrest was correlated with the modulation of the expression of cell cycle regulating proteins including cdc2 (Tyr15), cyclin A, cyclin B1 and cyclin E. The increase of sub-G1 peak by the higher concentrations of ochnaflavone (over
) was closely related to the induction of apoptosis, which was evidenced by the induction of DNA fragmentation, activation of caspase-3, -8 and -9, and cleavage of poly-(ADP-ribose) polymerase. These findings suggest that the cell cycle arrest and induction of apoptosis might be one possible mechanism of actions for the anti-proliferative activity of ochnaflavone in human colon cancer cells.
Fibronectin Induces Pro-MMP-2 Activation and Enhances Invasion in H-Ras-Transformed Human Breast Epithelial Cells
Kim, Jong-Sook ; Moon, A-Ree ;
Biomolecules and Therapeutics, volume 17, issue 3, 2009, Pages 288~292
DOI : 10.4062/biomolther.2009.17.3.288
Interactions between tumor cells and the extracellular matrix (ECM) strongly influence tumor development, affecting cell survival, proliferation and migration. Fibronectin, a major component of ECM, has been shown to interact with integrins especially the
integrin. Cell invasion and metastasis are often associated with matrix metalloproteinases (MMPs) which are capable of digesting the different components of the ECM and basement membrane. MMP-2 is produced as a latent pro-MMP-2 (72 kDa) to be activated, resulting the 62 kDa active MMP-2. In this study, we investigated the effect of fibronectin on activation of pro-MMP-2 and the cellular invasiveness in H-Ras-transformed MCF10A human breast epithelial cells. Here we show that fibronectin induces activation of pro-MMP-2 and up-regulation of MT1-MMP and TIMP-2 in H-Ras MCF10A cells. These results demonstrate that H-Ras MCF10A cells secrete high levels of active MMP-2 when cultured with fibronectin, suggesting a possible interaction between the ECM network and H-Ras MCF10A cells to generate active MMP-2 which is important for proteolysis and ECM remodeling. Invasive and migratory abilities of H-Ras MCF10A cells were enhanced by fibronectin. Fibronectin up-regulated the expression of
integrin which may play a role in cellular responses exerted by fibronectin. Since acquisition of pro-MMP-2 activation can be associated with increased malignant progression, this study provides a mechanism for the cell surface-matrix degrading effect of fibronectin which will be crucial to breast cell invasion and migration.
Extracellular Signal-Regulated Kinase Is a Major Enzyme in Korean Mistletoe Lectin-Mediated Regulation of Macrophage Functions
Byeon, Se-Eun ; Lee, Jae-Hwi ; Yu, Tao ; Kwon, Moo-Sik ; Hong, Sung-Youl ; Cho, Jae-Youl ;
Biomolecules and Therapeutics, volume 17, issue 3, 2009, Pages 293~298
DOI : 10.4062/biomolther.2009.17.3.293
Korean mistletoe lectin (KML) is the major component found in Viscum album var. (coloratum), displaying anti-cancer and immunostimulating activities. Even though it has been shown to boost host immune defense mechanisms, the regulatory roles of KML on the functional activation of macrophages have not been fully elucidated. In this study, regulatory mechanism of KML on macrophage-mediated immune responses was examined in terms of KML-mediated signaling event. KML clearly induced mRNA expression of tumor necrosis factor (TNF)-
, the generation of reactive oxygen species (ROS) and phagocytic uptake in RAW264.7 cells. All of these events were strongly suppressed by U0126, whereas TNF-
mRNA was not diminished by SB203580 and SP600125, indicating ERK as a central enzyme managing KML-induced up-regulation of macrophage functions. Indeed, KML strongly induced the phosphorylation of ERK in a time-dependent manner without altering its total level. Therefore, these data suggest that ERK may be a major signaling enzyme with regulatory property toward various KML-mediated macrophage responses.
Changes in the Pharmacokinetics of Rosiglitazone, a CYP2C8 Substrate, When Co-Administered with Amlodipine in Rats
Kim, Seon-Hwa ; Kim, Kyu-Bong ; Um, So-Young ; Oh, Yun-Nim ; Chung, Myeon-Woo ; Oh, Hye-Young ; Choi, Ki-Hwan ;
Biomolecules and Therapeutics, volume 17, issue 3, 2009, Pages 299~304
DOI : 10.4062/biomolther.2009.17.3.299
Rosiglitazone maleate (RGM) is widely used for improving insulin resistance. RGM is a moderate inhibitor of cytochrome P450 2C8 (CYP2C8) and is also mainly metabolized by CYP2C8. The aim of this study was to determine whether the effect of RGM on CYP2C8 is altered by co-treatment with other drugs, and whether amlodipine camsylate (AC) changes the pharmacokinetics (PK) of RGM. Of the 11 drugs that are likely to be co-administered with RGM in diabetic patients, seven drugs lowered the
value of RGM on CYP2C8 by more than 80%. In vitro CYP2C8 inhibitory assays of RGM in combination with drugs of interest showed that the
of RGM was decreased by 98.9% by AC. In a pharmacokinetic study, Sprague-Dawley (SD) rats were orally administered 1 mg/kg of RGM following by single or 10-consecutive daily administrations of 1.5 mg/kg/day of AC. No significant changes in the pharmacokinetic parameters of RGM were observed after a single administration of AC, but the AUC and
values of RGM were significantly reduced by 36% and 31%, respectively, by multiple administrations of AC. In conclusion, RGM was found to be affected by AC by in vitro CYP2C8 inhibition testing, and multiple dosing of AC appreciably changed the pharmacokinetics of RGM. These findings suggest that a drug interaction exists between AC and RGM.
Anti-Hyperalgesic Effects of Meloxicam Hydrogel via Phonophoresis in Acute Inflammation in Rats; Comparing Systemic and Topical Application
Kim, Tae-Youl ; Kim, Young-Il ; Seo, Sam-Ki ; Kim, Soo-Hyeun ; Yang, Kyu-Ho ; Shin, Sang-Chul ;
Biomolecules and Therapeutics, volume 17, issue 3, 2009, Pages 305~310
DOI : 10.4062/biomolther.2009.17.3.305
The aim of this study was to determine if a meloxicam hydrogel could be administered in vivo via phonophoretic transdermal delivery using pulsed ultrasound by examining its anti-hyperalgesic effects in a rat carrageenan inflammation model. Carrageenan (1%) was injected into the plantar surface of the right hindpaw, and meloxicam hydrogel was administered via phonophoretic transdermal delivery. Changes in the mechanical and thermal hyperalgesia, as well as swelling, showed that phonophoretic delivery of meloxicam exhibited significantly better anti-hyperalgesic and anti-inflammatory effects than pulsed ultrasound. Topical and systemic application of meloxicam hydrogel using phonophoresis showed similar anti-hyperalgesic effects. These findings suggest that the transdermal administration of a meloxicam hydrogel using phonophoresis by pulsed ultrasound might be useful for treating acute inflammation.
Negligible Effect of Ginkgo Biloba Extract on the Pharmacokinetics of Cilostazol
Chung, Hye-Jin ; Kim, Nam-Sun ; Kim, Eun-Jeong ; Kim, Tae-Kon ; Ryu, Keun-Ho ; Lee, Bong-Yong ; Kim, Dong-Hyun ; Jin, Chang-Bae ; Yoo, Hye-Hyun ;
Biomolecules and Therapeutics, volume 17, issue 3, 2009, Pages 311~317
DOI : 10.4062/biomolther.2009.17.3.311
Ginkgo biloba (G. biloba) extract is a widely used phytomedicine for the oral treatment of peripheral vascular disease. Cilostazol is a synthetic antiplatelet and vasodilating agent for the treatment of intermittent claudication resulting from peripheral arterial disease. It is likely to use concomitantly G. biloba extract and cilostazol for the treatment of peripheral arterial disease, which raises a concern of increasing their adverse effects of herbal-drug interactions. To clarify any possible herbal-drug interaction between G. biloba extract and cilostazol, the effect of the G. biloba extract on the pharmacokinetics of cilostazol was investigated. As cilostazol is known to be eliminated mainly by cytochrome P450 (CYP)-mediated metabolism, we investigated the effects of G. biloba extract on the human CYP enzyme activities and the effect of G. biloba extract on the pharmacokinetics of cilostazol after co-administration of the two agents to male beagle dogs. The G. biloba extract inhibited more or less CYP2C8, CYP2C9, and CYP2C19 enzyme activities in the in vitro microsomal study with
values of 30.8, 60.5, and
, respectively. In the pharmacokinetic study, co-administration with the G. biloba extract had no significant effect on the pharmacokinetics of cilostazol in dogs, although CYP2C has been reported to be responsible for the metabolism of cilostazol. In conclusion, these results suggest that there may not be a pharmacokinetic interaction between G. biloba extract and cilostazol.
Hepatotoxic Effects of 1-Furan-2-yl-3-pyridin-2-yl-propenone, a New Anti-Inflammatory Agent, in Mice
Jeon, Tae-Won ; Kim, Chun-Hwa ; Lee, Sang-Kyu ; Shin, Sil ; Choi, Jae-Ho ; Kang, Won-Ku ; Kim, Sang-Hyun ; Kang, Mi-Jeong ; Lee, Eung-Seok ; Jeong, Tae-Cheon ;
Biomolecules and Therapeutics, volume 17, issue 3, 2009, Pages 318~324
DOI : 10.4062/biomolther.2009.17.3.318
1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) has recently been synthesized and characterized to have an anti-inflammatory activity through the inhibition of the production of nitric oxide. In the present study, adverse effects of FPP-3 on hepatic functions were determined in female BALB/c mice. When mice were administered with FPP-3 at 125, 250 or 500 mg/kg for 7 consecutive days orally, FPP-3 significantly increased absolute and relative weights of liver with a dose-dependent manner. In addition, FPP-3 administration dramatically increased the hepatotoxicity parameters in serum at 500 mg/kg, in association of hepatic necrosis. FPP-3 significantly induced several phase I enzyme activities. To elucidate the possible mechanism(s) involved in FPP-3 induced hepatotoxicity, we investigated the hepatic activities of free radical generating and scavenging enzymes and the level of hepatic lipid peroxidation. FPP-3 treatment significantly elevated the hepatic lipid peroxidation, measured as the thiobarbituric acid-reactive substance, and the activity of superoxide dismutase. Taken together, the present data indicated that reactive oxygen species might be involved in FPP-3-induced hepatotoxicity.
Single Oral Dose Toxicity Test of Low Molecular Weight Fucoidan in Rats
Yoon, Hyun-Soo ; Shin, Yong-Kyu ; Jung, Young-Mi ; Lee, Hyeung-Sik ; Ku, Sae-Kwang ;
Biomolecules and Therapeutics, volume 17, issue 3, 2009, Pages 325~331
DOI : 10.4062/biomolther.2009.17.3.325
The object of this study was to evaluate the single oral dose toxicity of Low Molecular Weight Fucoidan (LMF) in male and female rats. LMF was administered to female and male SD rats as an oral dose of 2,000, 1,000 and 500 mg/kg (body wt.). Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation organ weight and histopathology of 14 principle organs were examined upon necropsy. As the results, no LMF treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principle organs were detected up to 2,000 mg/kg in both female and male rats except for some sporadic findings not LMF treatment related toxicological signs. Therefore,
(50% lethal dose) and approximate LD of LMF after single oral treatment in female and male rats were considered over 2,000 mg/kg - the limited dosages recommended by KFDA Guidelines [2005-60, 2005], respectively.