• Title/Summary/Keyword: Dose Reduction

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Protective Effect of a Herbal Preparation (HemoHIM) on the Self-Renewal Tissues and Immune System against γ-Irradiation (방사선에 대한 생약복합조성물(HemoHIM)의 재생조직 및 면역계 방호 · 회복촉진 효과)

  • Jo, Sung-Kee;Park, Hae-Ran;Jung, Uhee;Oh, Heon;Kim, Sung-Ho;Yee, Sung-Tae
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.34 no.6
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    • pp.805-813
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    • 2005
  • In our previous study, a novel herb mixture (HIM-I) of Angelim gigas radix, Cnidium officinale rhizoma, and Paeonia japonica radix was developed to protect the intestinal and immune systems and promote its recovery against radiation damage. In this study, a new herbal preparation (HemoHIM) with the high immune modulating activity was developed from HIM-I. HIM-I was fractionated into ethanol fraction (HIM-I-E) and polysaccharide fraction (HIM-I-P). And HemoHIM was prepared by adding HIM-I-P to HIM-I. The protective activities against $\gamma$ -irradiation were compared among HemoHIM, HIM-I and the fractions. HemoHIM and HIM-I significantly decreased the radiation-induced DNA damage in vitro, and scavenged hydroxyl radicals in a dose-dependent manner. HemoHIM showed similar activity to HIM-I. In vitro proliferation assay with mouse lymphocytes and bone marrow cells showed that HIM-I-P was remarkably higher than HIM-I and HIM-I-E in cell proliferating activity. HemoHIM showed higher activity than HIM-I and this might be associated with the higher polysaccharide content. The in vivo protective effects of HemoHIM and HIM-I were investigated in $\gamma$-irradiated mice. HemoHIM increased the surviving intestinal crypts to a similar extent compared with HIM-I. In contrast, HemoHIM appeared to be more effective than HIM-I in endogenous spleen colony formation assay. The recovery of white blood cells and lymphocytes in irradiated mice were significantly enhanced by the administration of HemoHIM. Also HemoHIM administration prolonged the survival of irradiated mice. These results showed that the novel herbal preparation, HemoHIM, effectively protected the self-renewal tissues and immune system, and promoted the survival of irradiated mice. Moreover, in comparison with HIM-I, HemoHIM maintained similar activity in the reduction of oxidative damage of self-renewal tissue but exhibited the higher activity in protection and proliferation of immune and hematopoietic cells. These results suggested that HemoHIM might be more effective than HIM-I in immune modulation as well as radioprotection.

Therapeutic Effects of Curdrania tricuspidata Leaf Extract on Osteoarthritis (골관절염 실험모델에서 꾸지뽕나무 추출물의 골관절염 억제효과 연구)

  • Nam, Da-Eun;Kim, Ok Kyung;Lee, Jeongmin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.5
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    • pp.697-704
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    • 2013
  • The inhibitory effect of ethanol extracts from Curdrania tricuspidata leaves (CTL) on osteoarthritis was investigated in primary cultured rat cartilage cells and a monosodium-iodoacetate (MIA)-induced arthritis rat model. To identify the effects of CTL 80% ethanol extracts (CTL80) and CTL 10% ethanol extracts (CTL10) against $H_2O_2$ treatment in vitro, cell survival was measured by the MTT assay. Cell survival after $H_2O_2$ treatment increased with CTL80 and CTL10 close to normal up to $300{\mu}g/mL\;H_2O_2$. The mRNA expression of matrix metalloproteinases (MMPs) was determined MMP-7 and MMP-13 (known catabolic factors), were significantly inhibited by CTL 80 and CTL10; a $200{\mu}g/mL$ dose of CTL80 especially decreased MMP-13 expression. In vivo, osteoarthritis was induced by an intra-articular injection of MIA into the knee joints of rats, then CTL80 and CTL10 orally administered daily for 35 days. After the animals were sacrificed, histological evaluations of their knee joints revealed a reduction in polymorphonuclear cell infiltration and smooth synovial lining in the CTL80-500 group. Micro-CT analysis of hind paws from CTL80-500 and CTL10 showed a protection against osteophyte formation, soft tissue swelling, and bone resorption. In conclusion, CTL ethanol extracts are effective in ameliorating joint destruction and cartilage erosion in MIA-induced rats. CTL decreases and normalizes articular cartilage through preventing extracellular matrix degradation and chondrocyte injury, and could potentially serve as a therapeutic treatment for humans.

Calcium Bioavailability and Antiosteoporotic Effects of Cheonggukjang Containing High Poly-Gamma Glutamate Contents (고함량 폴리감마글루탐산(PGA) 청국장에 대한 칼슘 생체이용률 및 골다공증에 미치는 영향)

  • Lee, Mu-Jin;Jung, Ho-Kyung;Sim, Mi-Ok;Jang, Ji-Hun;Kim, Tae-Mook;Lee, Hyun-Joo;Lee, Ki-Ho;An, Byeong-Kwan;Cho, Jung-Hee;Jang, Min-Cheol;Yong, Ju-Hyun;Kim, Jong-Choon;Cho, Hyun-Woo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.11
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    • pp.1544-1551
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    • 2016
  • Various types of fermented soybean foods are consumed in various Asian countries, including China, Indonesia, Japan, Korea, and Vietnam. Cheonggukjang is a Korean whole soybean paste fermented by Bacillus subtilis and regarded as a healthy food. The objective of this study was to investigate the Ca-bioavailability and anti-osteoporotic effects of cheonggukjang (CGJ) containing high poly-gamma glutamate (PGA) contents in an animal model. Blood samples were collected from the jugular vein at 0, 0.5, 1, 2, 3, 4, and 5 h after a single oral dose in male rats. Ca-bioavailability in CGJ containing high PGA contents was approximately 3~5 times higher than that of natural CGJ. Female rats were either sham-operated (sham; n=5) or surgically ovariectomized (OVX; five animals per group) and then administered to OVX control, raloxifene hydrochloride (RLX) 1 mg/kg/d, or CGJ containing high contents of PGA (20 and 200 mg/kg/d) for 12 weeks. Serum osteocalcin concentration was significantly lower in the CGJ 200 mg/kg/d group compared with the OVX control group. Serum progesterone concentration was significantly higher in the CGJ 200 mg/kg/d group compared with the OVX control group. Reduction grade of the trabecular bone decreased in the RLX 1 and CGJ 200 mg/kg/d group compared with that of the OVX control group. In conclusion, CGJ 200 mg/kg/d may have inhibitory effects on osteoporosis in OVX rats, and Ca-bioavailability was improved in CGJ containing high PGA contents.

Allium tuberosum Reverses PCSK9-Mediated LDLR Degradation by Inhibition of HNF1α (부추 추출물의 PCSK9 억제를 통한 LDL 콜레스테롤 저감 효능)

  • Choi, Hyo-Kyoung;Kim, Hyo Jin;Hwang, Jin-Taek;Chung, Min-Yu
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.11
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    • pp.1278-1285
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    • 2017
  • Accumulation of excess low density lipoprotein (LDL) cholesterol in the blood can initiate and accelerate atherosclerosis. Statins mediate the transactivation of proprotein convertase subtilisin/kexin type 9 (PCSK9), which in turn limits their cholesterol-lowering effects via LDL receptor (LDLR) degradation. The objective of this study was to investigate whether or not Allium tuberosum (AT) regulates LDLR and PCSK9. Mice were fed a low fat control diet (LD) or Western diet (WD) supplemented with AT (1%, w/w). AT significantly attenuated total and LDL cholesterol levels in mice fed WD (P<0.05). AT also significantly inhibited hepatic PCSK9 gene expression (P<0.05) while AT maintained hepatic LDLR gene expression. To further investigate AT-mediated PCSK9 regulation, HepG2 cells were treated with 10% delipidated serum (DLPS) in the presence or absence of AT. Non-toxic level of AT dose-dependently increased the LDLR protein level, and AT at $400{\mu}g/mL$ markedly inhibited PCSK9 protein expression. Similarly, AT significantly increased LDLR gene expression, whereas it significantly down-regulated PCSK9 gene expression. AT-mediated reduction of PCSK9 gene expression is likely due to decreased hepatic nuclear factor $1{\alpha}$ ($HNF1{\alpha}$) expression, but not SREBP2 in HepG2 cells under lipid-depleted conditions. AT-mediated PCSK9 inhibition contributed to LDLR protein stabilization via protection against LDLR lysosomal degradation in HepG2 cells under lipid-depleted conditions. Further investigation is warranted to determine the active components of AT and whether or not these components are effective in reducing hypercholesterolemia.

Effects of Postoperative Radiotherapy on Distribution of Bone Metastases in Breast Cancer (유방암환자에서 수술 후 방사선치료가 골전이 분포에 미치는 영향)

  • Kim, Bo-Kyoung;Ha, Sung-Whan
    • Radiation Oncology Journal
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    • v.19 no.3
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    • pp.211-215
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    • 2001
  • Purpose : This study was done to evaluate the efficacy of low-dose radiation in reduction of thoracic vertebral metastases in patients with breast cancer. Materials and Methods : 109 patients who were treated for bone metastasis from breast cancer from June, 1988 to June, 1998 in the Department of Therapeutic Radiology, Seoul National University were included. Of the 109 patients, 40 patients had been previously treated by postoperative radiotherapy and 69 had not. Postoperative radiotherapy had been given using Co-60 teletherapy device in 30 patients or 6 MV linear accelerator in 10. Thoracic spines from 1 to 10 were usually irradiated except in 1 patient and cervical vertebrae 6 and/or 7 were partially included in ,: patients. A total of 50.4 Gy was given with 1.8 Gy fraction. Metastatic bone diseases were scored in 11 regions, i. e., skull, conical spine, thoracic spine from 1 to 4, from 5 to 8, 9 and 10, 11 and 12, lumbar spine, pelvis, femur, ribs and others. Results : In no postoperative parasternal irradiation group, lumbar vertebrae were the most common metastatic sites $(55.1\%)$ followed by pelvis $(44.9\%)$, ribs $(40.6\%)$, thoracic vertebrae 11 and 12 $(37.7\%)$, thoracic vertebrae between 5 and 8 $(36.2\%)$, thoracic vertebrae 9 and 10 $(34.8\%)$, and thoracic vertebrae between 1 and 4 $(26.1\%)$. In postoperative parasternal irradiation group, lumbar vertebrae and pelvis were also the most common sites of metastases ($55.0\%$, respectively) followed by ribs $(37.5\%)$, and thoracic vertebrae 11 and 12 $(32.5\%)$. But significant less metastases were seen at thoracic vertebrae from 1 to 10. Conclusion : We can find that the were significantly less bony metastases at thoracic vertebrae which had been previously irradiated postoperatively.

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Anti-oxidative and Anti-cancer Activities of Ethanol Extract of Litsea populifolia (인체 폐암 세포주 A549에서 Litsea populifolia 추출물의 항산화 및 항암활성 분석)

  • Jin, Soojung;Oh, You Na;Jeong, Hyun Young;Yun, Hee Jung;Park, Jung-ha;Kwon, Hyun Ju;Kim, Byung Woo
    • Journal of Life Science
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    • v.29 no.6
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    • pp.679-687
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    • 2019
  • Litsea populifolia, a plant species of the Lauraceae family, is widely distributed in the tropical and subtropical areas of Asia. The phylogenetic relationships and botanical characteristics of L. populifolia have been reported; however, its anti-oxidative and anti-cancer activities remain unclear. In this study, we evaluated the anti-oxidative and anti-cancer effects of ethanol extracts of L. populifolia (EELP) together with the molecular mechanism of its anti-cancer activity in human lung adenocarcinoma A549 cells. EELP showed significant anti-oxidative effects with a 50% inhibitory concentration at $11.71{\mu}g/ml$, which was measured by the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay. EELP exhibited cytotoxic activity and induced cell cycle arrest at the G1 phase in A549 cells in a dose-dependent manner, whereas EELP did not have the cytotoxic effect on the normal human lung cell line IMR90. Treatment with EELP also resulted in a decreased expression of G1/S transition-related molecules-including cyclin-dependent kinase (CDK) 2, CDK6, cyclin D1, and cyclin E-both for the transcription and translation levels. EELP-induced G1 arrest was associated with the phosphorylation of checkpoint kinase 2 (CHK2), p53, cell division cycle 25 homolog A (CDC25A), and the reduction of CDC25A expression in A549 cells. Collectively, these results suggest that EELP may exert an anti-cancer effect by cell cycle arrest at the G1 phase through both p53-dependent and p53-independent (ATM/CHK2/CDC25A/CDK2) pathways in A549 cells.

Toxicity Assessment of Antifouling Agent using the Survival and Population Growth Rate of Marine Rotifer, Brachionus plicatilis (해산로티퍼(Brachionus plicatilis)의 생존 및 개체군 성장률을 이용한 신방오도료(Zinc undecylenate)의 독성평가)

  • Hwang, Un-Ki;Choi, Hoon;Park, Yun-Ho;Park, Na-Young;Jang, Soo-Jung;Lee, Seung Min;Choi, Yun-Seok;Yang, Joon-Yong;Lee, Ju-Wook
    • Korean Journal of Environmental Biology
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    • v.36 no.3
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    • pp.392-399
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    • 2018
  • Toxicity assessment of antifouling agent, zinc undecylenate (ZU) has been investigated using the rate of survival and population growth in marine rotifer, Brachionus plicatilis. The survival rate of Brachionus plicatilis was determined after 24 h of exposure to ZU and was not affected up to the maximum level of $100.0mg\;L^{-1}$ of ZU. The population growth rate (r) was determined after 72 h of exposure to ZU. It was observed that r in the controls (absence ZU) was greater than 0.5 but exhibited a sudden decrease with an increase in the concentration of ZU. ZU reduced r in a dose-dependent manner and a significant reduction occurred at a concentration greater than $12.5mg\;L^{-1}$. The 50% effective concentration ($EC_{50}$) value of r during ZU exposure was $26.4mg\;L^{-1}$, No-observed-effect-concentration (NOEC) was $6.3mg\;L^{-1}$ and Lowest-observed-effect-concentration (LOEC) was $12.5mg\;L^{-1}$, respectively. Based on the results, it is apparent that ZU concentration greater than $12.5mg\;L^{-1}$ exhibited a toxic effect on the r of zooplankton, B. plicatilis in natural ecosystems.

Activity-guided Purification of N-benzyl-N-methyldecan-1-amine from Garlic and Its Antitumor Activity against CT-26 Colorectal Carcinoma in BALB/C Mice (활성추적분리법에 의해서 순수분리한 마늘 N-benzyl-N-methyldecan-1-amine이 CT-26 세포주 이식 BALB/C mice의 항암효과)

  • Seetharaman, Rajasekar;Choi, Seong Mi;Guo, Lu;Cui, Zheng Wei;Otgonbayar, Duuriimaa;Park, Ju Ha;Kwon, Young-Seok;Kwak, Jung Ho;Kwon, Young Hee;Min, Ji Hyun;Kang, Jum Soon;Choi, Young Whan
    • Journal of Life Science
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    • v.29 no.10
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    • pp.1062-1070
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    • 2019
  • A components of garlic (Allium sativum) have anti-proliferative effects against various types of cancer. We aimed to investigate the capacity of garlic compounds to anti-tumor on a various cancer cell lines. Fractionation of garlic extract, guided by antiproliferative activity against human gastric cancer (AGS) cells, has resulted in the isolation of N-benzyl-N-methyldecan-1-amine (NBNMA). We investigated the effect of newly isolated NBNMA from garlic cloves on the inhibition of the growth of CT-26, AGS, HepG2, HCT-116, MCF7, B16F10, and Sarcoma-180 cells for in vitro and CT-26 colon carcinoma cells in vivo. NBNMA exhibited an antiproliferative effect in CT-26 cells by apoptotic cell death. NBNMA exhibited down-regulation of anti-apoptotic Bcl-2 proteins and up-regulation of apoptotic Bad protein expression in western blot analyses. In addition, NBNMA meagre activated caspase 3 and caspase 9, initiator caspases of the extrinsic and intrinsic pathways of apoptosis. NBNMA treatment at a dose of 10 mg/kg for 21 days in experimental mice implanted with tumors resulted in significant reduction of the tumor weight (43%). NBNMA exhibited both in vitro and in vivo anticancer activity. These results indicate that NBNMA has promising potential to become a novel anticancer agent from garlic cloves for the treatment of colon carcinoma cancer.

Neuroprotective effect of fermented ginger extracts by Bacillus subtilis in SH-SY5Y cells (고초균에 의한 생강 발효 추출물의 신경세포 보호 효과)

  • Yang, Hee Sun;Kim, Mi Jin;Kim, Mina;Choe, Jeong-sook
    • Journal of Nutrition and Health
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    • v.54 no.6
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    • pp.618-630
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    • 2021
  • Purpose: The ginger rhizome (Zingiber officinale) is widely cultivated as a spice for its aromatic and pungent components. One of its constituents, 6-hydroxydopamine (6-OHDA) is usually thought to cross the cell membrane through dopamine uptake transporters, and induce inhibition of mitochondrial respiration and the generation of intracellular reactive oxygen species (ROS). This study examines the neuroprotective effect and acetylcholinesterase (AChE) inhibitory activity of fermented ginger extracts (FGEs) on 6-OHDA induced toxicity in SH-SY5Y human neuroblastoma cells. Methods: Ginger was fermented using 2 species of Bacillus subtilis, with or without enzyme pretreatment. Each sample was extracted with 70% ethanol. Neurotoxicity was assessed by applying the EZ-Cytox cell viability assay and by measuring lactic dehydrogenase (LDH) release. Morphological changes of apoptotic cell nuclei were observed by Hoechst staining. Cell growth and apoptosis of SH-SY5Y cells were determined by Western blotting and enzyme activity analysis of caspase-3, and AChE enzymatic activity was determined by the colorimetric assay. Results: In terms of cell viability and LDH release, exposure to FGE showed neuroprotective activities against 6-OHDA stimulated stress in SH-SY5Y cells. Furthermore, FGE reduced the 6-OHDA-induced apoptosis, as determined by Hoechst staining. The occurrence of apoptosis in 6-OHDA treated cells was confirmed by determining the caspase-3 activity. Exposure to 6-OHDA resulted in increased caspase-3 activity of SH-SY5Y cells, as compared to the unexposed group. However, pre-treatment with FGE inhibited the activity of caspase-3. The neuroprotective effects of FGE were also found to be caspase-dependent, based on reduction of caspase-3 activity. Exposure to FGE also inhibited the activity of AChE induced by 6-OHDA, in a dose-dependent manner. Conclusion: Taken together, our results show that FGE exhibits a neuroprotective effect in 6-OHDA treated SH-SY5Y cells, thereby making it a potential novel agent for the prevention or treatment of neurodegenerative disease.

Effect of Heavy Metals (As, Cr, Pb) on the Population Growth Rates of Marine Diatom, Skeletonema castatum (중금속(As, Cr, Pb)이 해산 규조류(Skeletonema costatum)의 개체군 성장률에 미치는 영향)

  • Lee, Ju-Wook;Ryu, Hyang-Mi;Heo, Seung;Jang, Soo-Jung;Lee, Ki-won;Hwang, Un-Ki
    • Journal of Marine Life Science
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    • v.2 no.1
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    • pp.20-26
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    • 2017
  • In this study, we evaluated the toxic effects of heavy metals (As, Cr and Pb) on the population growth rate (r) of the marine diatom, Skeletonema costatum. The r of the species was determined after 96 h (4 days) exposure to As (0, 0.31, 0.63, 1.25, 2.50 and 5.00 mg L-1), Cr (0, 0.16, 0.31, 0.63, 1.25 and 2.50 mg L-1) and Pb (0, 1.25, 2.50, 5.00, 10.00 and 20.00 mg L-1). It was observed that r in the control (absence of As, Cr and Pb) were greater than 0.04, however suddenly decreased with increased heavy metal concentrations. As, Cr and Pb reduced r in a dose-dependent manner and a significant reduction were occurred at concentration of greater than 0.31, 0.31 and 5.00 mg L-1, respectively. Based on the toxicity, the heavy metal were ranked as Cr>As>Pb, with EC50 (50% effective concentration) values of 0.80, 2.57 and 13.88 mg L-1, respectively. The lowest-observed-effective-concentration (LOEC) of r in exposed to As, Cr and Pb were 0.63, 0.63 and 10.00 mg L-1, respectively. Precisely, a concentration of greater than 0.63 mg L-1 of As, 0.63 mg L-1 of Cr and 10.00 mg L-1 of Pb in marine ecosystems induced toxic effect on the r of S. costatum. Based on our results, we suggested that the r of S. costatum might be a useful bio-indicator for the toxicity assessment of heavy metals on the producer in marine ecosystems.