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Synergistic interactions of Aegle marmelos leaf, Emblica officinalis fruit and Ocimum sanctum leaf extracts in the regulation of hyperthyroidism and / or hyperglycaemia

  • Panda, Sunanda;Kar, Anand
    • Advances in Traditional Medicine
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    • v.4 no.1
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    • pp.37-43
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    • 2004
  • The effects of Aegle marmelos (Rutaceae) leaf, Emblica officinalis (Euphorbiaceae) fruit and Ocimum sanctum. (Labiateae) leaf extracts were studied in L-thyroxine (0.5 mg/kg) induced hyperthyroidic mice. Separately combined effects of these three plant extracts and of a commonly used antithyroidic drug, Propyl thiouracil (PTU) were investigated for comparison. Serum concentration of thyroxine $(T_4)$, triiodothyronine $(T_3)$, glucose and the activity of hepatic Glucose 6-Phosphatase (G-6-Pase) were considered as main parameters. Hepatic lipid peroxidation (LPO), superoxide dismutase (SOD) and Catalase (CAT) activities were also studied to reveal the toxic effect of the plant extracts, if any. While exogenous $T_4$ enhanced serum concentration of $T_4$, $T_3$, glucose and the activity of hepatic G-6-Pase, a simultaneous administration of either A. marmelos leaf (1.0 mg/kg), E. officinalis fruit( 30 mg/kg) and O. sanctum leaf (50 mg/kg) extracts, to hyperthyroidic animals decreased all these parameters. However, the effects were more pronounced, as nearly normal thyroid function and serum glucose concentration were exhibited when all three plant extracts were administered together. A decrease in LPO and a concomitant increase in SOD and the CAT activities indicated the safe and antiperoxidative nature of the plant extracts, administered either alone or in combination. Our findings reveal that the three test plant materials exhibit synergistic effects without any hepatotoxicity, suggesting their potential use in the amelioration of hyperthyroidism and/ or hyperglycaemia.

Inhibitory Effect of Daesiho-tang(Dachaihu-tang) Extracts on High-fat Diet-induced Obesity (고지방 식이 유도 비만에 대한 대시호탕 추출물의 억제 효과)

  • Song, Mi-Young;Kim, Eun-Kyung;Kong, Jae-Cheol;Lee, Jeong-Han;Shin, Byung-Cheul;Ryu, Do-Gon;Kwon, Kang-Beom
    • Journal of Korean Medicine Rehabilitation
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    • v.18 no.3
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    • pp.41-49
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    • 2008
  • Objectives : The aim of this study is to investigate Daesiho-tang(Dachaihu-tang) water extracts (DSTE) have potent anti-obesity activities in a high-fat diet-induced obesity mouse model. Methods : In this study, we designed three groups (normal diet group, high-fat diet group, high-fat diet plus DSTE group for 7-weeks oral administration). Results : Increases in body weight were inhibited by 7-weeks oral administration of DSTE at a 500 mg/kg concentration in this animal model. Results from blood lipid analysis showed that the levels of triglyceride, total cholesterol and LDL-cholesterol were significantly lowered by DSTE administration, also HDL-cholesterol was increased more than high-fat diet-induced obese mouse. To understand the underlying mechanism at the molecular level, the effects of DSTE were examined on the expression of the genes involved in lipogenesis by real-time PCR. In epididymal fat and liver of DSTE-treated mice, the mRNA level of lipogenic genes such as sterol regulatory element binding protein 1 and fatty acid synthase were decreased, which was well correlated with the reduction of the tissues weight. Conclusions : These results suggest that DSTE may have great potential as a novel anti-obesity agent.

A Study of the Effect on Obesity in Taeeumin Animal-experimental Model Induced Lung Fibrosis with Bleomycin (Bleomycin으로 유발한 폐약(肺弱) 태음인 동물 모델에서의 비만에 대한 영향 평가)

  • Kim, Yoonha;Park, Junghwan;Kwak, Jinyoung;Park, Jungmi;Ahn, Taek won
    • Journal of Sasang Constitutional Medicine
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    • v.28 no.2
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    • pp.147-162
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    • 2016
  • Objectives The objective of this study is to develop a taeeumin animal-experimental model induced lung fibrosis with Bleomycin and evaluate the effect on obesity in this animal-experimental model.Methods The subjects were divided into 3 groups : normal group, high fat diet(HFD) control group, and HFD group administered with bleomycin(n=10 per group). To develop taeeumin animal-experimental model with reduced respiratory metabolism, 8-week-old C57BL/6 mice were administered with 0.03ml solution of bleomycin 1U/ml dissolved in distilled water, intratracheal(IT), once. Then, the HFD control group and the experimental group were fed with high fat diet for 6 weeks. Airway hyperresponsiveness(AHR) to methacholine was measured at the 1st and 3rd week after bleomycin was administered. Food intake and body weight were measured at regular time weekly. After the final experiment, blood was gathered by cardiac puncture for bloodchemical examination and organs(liver, fatty tissue) were remoed, weighted, and mRNA was analyzed.Results and Conclusions Through the experiment, it was found that Bleomycin induced Taeeumin animal-experimental models have leptin resistace. In the experimental group administered with Bleomycin, fatty acid synthesizing gene expression increased and energy metabolizing gene expression decreased. As mRNA expression of adiponectin decreased, it was found that Taeeuim animal-experimental model is susceptible to metabolic syndrome and cardiovascular diseases.

Anti-Metastatic Activity of Glycoprotein Fractionated from Acanthopanax senticosus, Involvement of NK-cell and Macrophage Activation

  • Ha, Eun-Suk;Hwang, Soo-Hyun;Shin, Kwang-Soon;Yu, Kwang-Won;Lee, Keyong-Ho;Choi, Joo-Sun;Park, Woo-Mun;Yoon, Taek-Joon
    • Archives of Pharmacal Research
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    • v.27 no.2
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    • pp.217-224
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    • 2004
  • Previously, we reported that water-extracted Acanthopanax senticasus exhibited anti-meta-static activity by stimulating the immune system. In this study, we fractionated glycoproteins (EN-SP) from the soluble protein layer (GF-AS) of A. senticasus and determined their basic chemical properties. We also investigated the anti-tumor and immunostimulating activities of the fractionated glycoprotein, EN-SP. We found that intravenous (i.v.) administration of GF-AS dramatically inhibited metastasis of colon26-M3.1 carcinoma cells to the lung in a dose-dependent manner. In vitro analysis showed GF-AS to enhance the proliferation of splenocytes. GF-AS also stimulated peritoneal macrophage, which was followed by the production of various cytokines such as IL-1$\beta$, TNF-$\alpha$, IL-12 and IFN-${\gamma}$. Furthermore, the production of these cytokines was partially blocked when peritoneal macrophage was cultured with the polyclonal antibodies against GF-AS. The depletion of NK cells by rabbit anti-asialo GM1 serum partly abolished the inhibitory effect of GF-AS on lung metastasis of colon26-M3.1 cells. Using gel filtration, EN-SP, an active glycoprotein fraction, is isolated from GF-AS. While both GF-AS and EN-SP stimulated the proliferatation of splenocytes of normal mice, EN-SP showed higher anti-metastatic activity and more potently stimulated the proliferation of splenocytes compared to GF-AS. These results suggest the use of EN-SP, the fractionated glycoprotein from A. senticasus, can be used as a therapeutical reagent to prevent or inhibit tumor metastasis.

Reduced EGFR Level in eIF2α Phosphorylation-Deficient Hepatocytes Is Responsible for Susceptibility to Oxidative Stress

  • Kim, Mi-Jeong;Choi, Woo-Gyun;Ahn, Kyung-Ju;Chae, In Gyeong;Yu, Rina;Back, Sung Hoon
    • Molecules and Cells
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    • v.43 no.3
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    • pp.264-275
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    • 2020
  • Reactive oxygen species (ROS) play a significant role in intracellular signaling and regulation, particularly when they are maintained at physiologic levels. However, excess ROS can cause cell damage and induce cell death. We recently reported that eIF2α phosphorylation protects hepatocytes from oxidative stress and liver fibrosis induced by fructose metabolism. Here, we found that hepatocyte-specific eIF2α phosphorylation-deficient mice have significantly reduced expression of the epidermal growth factor receptor (EGFR) and altered EGFR-mediated signaling pathways. EGFR-mediated signaling pathways are important for cell proliferation, differentiation, and survival in many tissues and cell types. Therefore, we studied whether the reduced amount of EGFR is responsible for the eIF2α phosphorylation-deficient hepatocytes' vulnerability to oxidative stress. ROS such as hydrogen peroxide and superoxides induce both EGFR tyrosine phosphorylation and eIF2α phosphorylation. eIF2α phosphorylation-deficient primary hepatocytes, or EGFR knockdown cells, have decreased ROS scavenging ability compared to normal cells. Therefore, these cells are particularly susceptible to oxidative stress. However, overexpression of EGFR in these eIF2α phosphorylation-deficient primary hepatocytes increased ROS scavenging ability and alleviated ROS-mediated cell death. Therefore, we hypothesize that the reduced EGFR level in eIF2α phosphorylation-deficient hepatocytes is one of critical factors responsible for their susceptibility to oxidative stress.

Microarray Analysis of Oxygen-Glucose-Deprivation Induced Gene Expression in Cultured Astrocytes

  • Joo, Dae-Hyun;Han, Hyung-Soo;Park, Jae-Sik
    • The Korean Journal of Physiology and Pharmacology
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    • v.10 no.5
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    • pp.263-271
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    • 2006
  • Since astrocytes were shown to play a central role in maintaining neuronal viability both under normal conditions and during stress such as ischemia, studies of the astrocytic response to stress are essential to understand many types of brain pathology. The micro array system permitted screening of large numbers of genes in biological or pathological processes. Therefore, the gene expression patterns in the in vitro model of astrocytes following exposure to oxygen-glucose deprivation (OGD) were evaluated by using the micro array analysis. Primary astrocytic cultures were prepared from postnatal Swiss Webster mice. The cells were exposed to OGD for 4 hrs at $37^{\circ}C$ prior to cell harvesting. From the cultured cells, we isolated mRNA, synthesized cDNA, converted to biotinylated cRNA and then reacted with GeneChips. The data were normalized and analyzed using dChip and GenMAPP tools. After 4 hrs exposure to OGD, 4 genes were increased more than 2 folds and 51 genes were decreased more than 2 folds compared with the control condition. The data suggest that the OGD has general suppressive effect on the gene expression with the exception of some genes which are related with ischemic cell death directly or indirectly. These genes are mainly involved in apoptotic and protein translation pathways and gap junction component. These results suggest that microarray analysis of gene expression may be useful for screening novel molecular mediators of astrocyte response to ischemic injury and making profound understanding of the cellular mechanisms as a whole. Such a screening technique should provide insights into the molecular basis of brain disorders and help to identify potential targets for therapy.

Immunoadjuvant Activity of Korean Mistletoe Lectin B-chain (한국산 겨우살이 Lectin B-chain의 면역증강 효과)

  • Her, Sun-Mi;An, Hyo-Sun;Kim, Kyu-Dae;Kim, Young-Hoon;Kim, In-Bo;Yoon, Taek-Joon;Kim, Jong-Bae
    • Korean Journal of Pharmacognosy
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    • v.42 no.3
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    • pp.246-252
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    • 2011
  • Korean mistletoe Lectin (KML-C) is composed of A and B sub-chain. B chain binds to carbohydrates on cell surface and A chain hinders translation and induces an apoptosis as a RIP (ribosome inactivating protein). KML-C has very strong biological activities, it has seriously limits to use as a cancer therapy or adjuvant because of its toxicity to normal cells. This study is therefore conducted to see if B chain of KML-C might have immunological activity, especially adjuvant activities with less toxicity. We isolated B chain from KML-C using the lactose affinity chromatography, and examined their immunoadjuvant activity. The isolated B-chain did not show any cytotoxicity against tumor cell, RAW264.7, and P388D1 while KML-C had a very strong toxicity. This non-toxic effect was observed also by in-vivo study. Both humoral and cellular immunities were observed ; the antibody titer was increased when the mice were immunized with B-chain used as adjuvant like Freund's adjuvant, indicating that B chain of mistletoe lectin alone might be used for adjuvant; it also increased DTH in cellular immunity. These results suggest that B-chain of KML-C might be used for adjuvant used for the production of antibody or vaccine with less toxicity.

Osteogenic Differentiation of Human Adipose-derived Stem Cells within PLGA(Poly(D,L-lactic-co-glycolic acid)) Scaffold in the Nude Mouse (누드 마우스에서 Poly(D,L-lactic-co-glycolic acid) (PLGA) 지지체 내 인체 지방줄기세포의 골성분화)

  • Yoo, Gyeol;Cho, Sung Don;Byeon, Jun Hee;Rhie, Jong Won
    • Archives of Plastic Surgery
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    • v.34 no.2
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    • pp.141-148
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    • 2007
  • Purpose: The object of this study was to evaluate the development of continuous osteogenic differentiation and bone formation after the subcutaneous implantation of the tissue-engineered bone, in vitro. Methods: Human adipose-derived stem cells were obtained by proteolytic digestion of liposuction aspirates. Adipose-derived stem cells were seeded in PLGA scaffolds after being labeled with PKH26 and cultured in osteogenic differentiation media for 1 month. The PLGA scaffolds with osteogenic stimulated adipose-derived stem cells were implanted in subcutaneous layer of four nude mice. Osteogenesis was assessed by RT-PCR for mRNA of osteopontin and bone sialoprotein(BSP), and immunohistochemistry for osteocalcin, and von Kossa staining for calcification of extracellular matrix at 1 and 2 months. Results: Implanted PLGA scaffold with adipose-derived stem cells were well vascularized, and PLGA scaffolds degraded and were substituted by host tissues. The mRNA of osteopontin and BSP was detected by RT-PCR in both osteogenic stimulation group and also osteocalcin was detected by immunohistochemistry at osteogenic stimulation 1 and 2 months, but no calcified extracellular deposit in von Kossa stain was found in all groups. Conclusion: In vivo, it could also maintain the characteristics of osteogenic differentiation that adipose-derived stem cells within PLGA scaffold after stimulation of osteogenic differentiation in vitro, but there were not normal bone formation in subcutaneous area. Another important factor to consider is in vivo, heterologous environment would have negative effect on bone formation as.[p1]

The effects of Far-infrared on Type II collagen induced mouse and the relative cytokine computerize programming (Emphasis on TNF-a and IL-1b) (원적외선이 관절염 흰쥐 모델에 미치는 영향과 관련 싸이토카인 예측 프로그래밍)

  • Kim Jae Yoon;Kim Jin-Sang;Bae Sung Soo;Park Rae Joon
    • The Journal of Korean Physical Therapy
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    • v.15 no.1
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    • pp.38-60
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    • 2003
  • The purpose of this study was to observe the effects of Far-infrared on mice rheumatoid arthritis induced by type II collagen. The author peformed several experimental tests which were the hematoxylin-eosin tissue stain, the hind paw thickness, and ELSIA of cytokines(TNF-$\alpha$, IL-1$\beta$). On day 14 and 21, FIR-Tx. group decreased in synovial membrane thickness more than control II group FIR-Tx group decreased in hind paw thickness more than control II group. In the ELISA test of TNF-$\alpha$ concentration, control II group significantly increased in the concentration more than normal and FIR-Tx. group on day 7, 14, and 21. In the ELISA test of IL-$\beta$ concentration, FIR-Tx. group decreased in the concentration more than control II group on day 14 and 21. With J's Linear Function Data Process Program, researchers can get the estimated the concentration or the hind paw thickness from this experiment. The estimated results would be a good guide to therapists and researchers, planning Far-infrared application on the rheumatoid arthritis. These results indicated that far-infrared irradiating appeared to reduce the concentration of TNF-$\alpha$ and IL-1$\beta$ at mouse model of autoimmune arthritis. It would be considered that Far-infrared has an effect on relieving rheumatoid arthritis.

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The Characteristics of Antitumor Agent Isolated from Streptomyces sp.409 (Streptomyces sp.409 에서 분리한 항암활성 물질의 특징)

  • 장영수
    • YAKHAK HOEJI
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    • v.44 no.5
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    • pp.478-487
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    • 2000
  • This study was carried out to find new anti-tumor agent producing microbe and to characterize the anti-tumor agent produced from the microbe. Purified compound that has a high cytotoxicity against tumor cell-lines could be obtained from the broth culture filtrates of Streptomyces sp.409 strain isolated from soil in Korea. The in vitro cytotoxicity the in vivo evaluation of acute toxicity the safety assessment of the anti-tumor compounds and the taxonomic characteristics of the anti-tumor agent were measured. The antitumor compound 1 and 2 were obtained from the broth culture filtrates of Streptomyces sp.409 strain. The cytotoxicity of the compound 1 against tumor cell-line P388D$_1$ showed almost 4.5 times higher than that of adriamycin. However in the cytotoxicity against normal cell line Vero E6, adriamycin showed adversely 4 times higher than the compound 1 ($IC_{50}$/ value: 228.7 $\mu\textrm{g}$/$m\ell$). In comparison study with compound 1 and compound 2 in the in vitro cytotoxin productivity against tumor cell lines, $IC_{50}$/ value of the compound 1 was 0.25 $\mu\textrm{g}$/$m\ell$ in tumor cell line P388D$_1$and 0.53 $\mu\textrm{g}$/$m\ell$ in tumor cell-line L1210, and that of the compound 2 was 7.18 $\mu\textrm{g}$/$m\ell$ and 35.71 $\mu\textrm{g}$/$m\ell$, respectively; LD$_{50}$ value of the compound 1 in the in vivo acute toxicity in mice was 22.62 $\mu\textrm{g}$/kg body weight. These results suggest that compound 1 purified from Streptomyces sp. 409 has anti-tumor activity and will be developed as an anti-tumor drug.g.

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