• Title/Summary/Keyword: Animal disease model

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Improving Effects of Platycodon Extracts Jelly on β-amyloid-induced Cytotoxicity and Scopolamine-Induced Cognitive Impairment Animal Models (도라지 추출물 연양갱이 β-amyloid에 의한 세포독성 및 Scopolamine에 의해 유도된 인지능 저하 동물 모델의 개선효과)

  • Oh, Hong-Geun;Kim, Jung-Hoon;Shin, Eun-Hye;Kang, Young-Rye;Lee, Bong-Gun;Park, Sang-Hoon;Moon, Dae-In;Kwon, Lee-Seong;Kim, Yong-Phill;Choi, Min-Hyu;Kim, Ok-Jin;Park, Kwang-Hyun;Lee, Hak-Yong
    • Korean Journal of Plant Resources
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    • v.26 no.4
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    • pp.417-425
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    • 2013
  • The aim of this study was to examine improving effect of Platycodon extracts (PE) and/or Platycodon extracts jelly (PEJ) on cognitive impairment in vitro and in vivo. PC12 (Pheochromocytoma) cells were pretreated with PE for 1hr and than incubated with $50{\mu}M$ amyloid ${\beta}(A{\beta})_{25-35}$ for additional 48hr. Cell viability was assessed by WST-1. Animals for Morris water test and passive avoidance test were divided into normal, control and two Platycodon extracts treated groups that were named Normal (n=7), Control (0 mg/kg, n=7), PE (300 mg/kg, n=7), PEJ (10 g/kg, n=7). Cognitive impairment was induced by scopolamine (1 mg/kg/body weight, i.p.) in the three experimental groups but not the normal group. Pretretment of PE (0.01-1 mg/mL) were not induced cytotoxicity but observed in high dose-treated group (5 and 10 mg/mL) in PC12 cells. Protective effects of PE against $A{\beta}$-induced cytotoxicity were increased in dose dependent manner in PC12 cells. Administration of PE and PEJ were significantly reduced escape latency time on Morris water maze test and passive avoidance test in copolamine-induced cognitive impairment animal model. These results suggest that Platycodon extracts and its related product available to ameliorative purpose for cognitive ability impairments.

Preparation of Alzheimers Animal Model and Brain Dysfunction Induced by Continuous $\beta$-Amyloid Protein Infusion

  • Akio Itoh;Kiyofumi Yamada;Kim, Hyoung-Chun;Toshitaka Nabeshima
    • Toxicological Research
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    • v.17
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    • pp.47-57
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    • 2001
  • Alzheimer's disease (AD) is the most common cause of dementia in the elderly, and its pathology is characterized by the presence of numerous numbers of senile plaques and neurofibrillary tangles. Several genetic and transgenic studies have indicated that excess amount of $\beta$-amyloid protein (A$\beta$) is produced by mutations of $\beta$TEX>$\beta$-amyloid precursor protein and causes learning impairment. Moreover, $A\beta$ has a toxic effect on cultured nerve cells. To prepare AD model animals, we have examined continuous (2 weeks) infusion of $A\beta$ into the cerebral ventricle of rats. Continuous infusion of $A\beta$ induces learning impairment in water maze and passive avoidance tasks, and decreases choline acetyltransferase activity in the frontal cortex and hippocampus. Immunohistochemical analysis revealed diffuse depositions of $A\beta$ in the cerebral cortex and hippocampus around the ventricle. Furthermore, the nicotine-evoked release of acetylcholine and dopamine in the frontal cortex/hippocampus and striatum, respectively, is decreased in the $A\beta$-infused group. Perfusion of nicotine (50 $\mu\textrm{M}$) reduced the amplitude of electrically evoked population spikes in the CA1 pyramidal cells of the control group, but not in those of the $A\beta$-infused group, suggesting the impairment of nicotinic signaling in the $A\beta$-infused group. In fact, Kd, but not Bmax, values for [$^3H$] cytisine binding in the hippocampus significantly increased in the $A\beta$-infused rats. suggesting the decrease in affinity of nicotinic acetylcholine receptors. Long-term potentiation (LTP) induced by tetanic stimulations in CA1 pyramidal cells, which is thought to be an essential mechanism underlying learning and memory, was readily observed in the control group, whereas it was impaired in the $A\beta$-infused group. Taken together, these results suggest that $A\beta$ infusion impairs the signal transduction mechanisms via nicotinic acetylcholine receptors. This dysfunction may be responsible, at least in part, for the impairment of LTP induction and may lead to learning and memory impairment. We also found the reduction of glutathione- and Mn-superoxide dismutase-like immunoreactivity in the brains of $A\beta$-infused rats. Administration of antioxidants or nootropics alleviated learning and memory impairment induced by $A\beta$ infusion. We believe that investigation of currently available transgenic and non-transgenic animal models for AD will help to clarify the pathogenic mechanisms and allow assessment of new therapeutic strategies.

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In Vitro and In Vivo Anti-Oxidative and Anti-Inflammatory Activities of Acer tegmentosum Maxim Extracts (RAW 264.7 대식세포와 염증유도 동물모델에서 산겨릅나무 추출물의 항산화 및 항염증 효과)

  • Lee, Cho-Eun;Jeong, Hyeon-Hee;Cho, Jin-Ah;Ly, Sun Yung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.1
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    • pp.1-9
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    • 2017
  • Acer tegmentosum Maxim (ATM) is known as traditional medicine for treatment of hepatic disorders such as hepatitis, related-inflammatory disease, and hepatic cancer. In this study, we evaluated the antioxidant and anti-inflammatory effects of ATM extracted with $80^{\circ}C$ water or 95% ethanol. Antioxidant activities of ATM extracts were measured based on DPPH and ABTS radical scavenging activities, total polyphenolic compound contents, and ferric reducing antioxidant power. The anti-inflammatory effects of ATM extract were assayed on release of nitric oxide, tumor necrosis factor $(TNF)-{\alpha}$, and interferon $(IFN)-{\gamma}$ from lipopolysaccharide (LPS)-induced macrophages. In these experiments, 95% ethanol extract of ATM showed stronger antioxidant and anti-inflammatory effects than water extract. Therefore, we determined the effects of ATM ethanol extract on an animal model of sepsis. Seven days oral gavage of ATM ethanol extract followed by LPS stimulation reduced the protein levels of $TNF-{\alpha}$ and $IFN-{\gamma}$ in serum as well as mRNA levels of $TNF-{\alpha}$ and interleukin-6 in intestinal epithelial cells. In addition, ATM ethanol extract reduced DNA damage in mouse lymphocytes. These results indicate that ATM extract has strong antioxidant and anti-inflammatory in vitro and in vivo effects and may be developed as a potential food material for prevention of inflammatory diseases.

The Second Animal Tests of Artificial Heart Valves (인공심장판막의 개발과 동물실험 -인공심장판막의 2차 동물실험-)

  • 김형묵
    • Journal of Chest Surgery
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    • v.23 no.4
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    • pp.617-621
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    • 1990
  • A heart supplies blood of about 15, 000 liters to each human organ in a day. A normal function of heart valves is necessary to accomplish these enormous work of heart. The disease of heart valve develops to a narrowness of a closure, resulting in an abnormal circulation of blood. In an attempt to eliminate the affliction of heart valves, the operative method to replace with artificial heart valves has developed and saved numerous patients over past 30 years. This replacement operation has been performed since early 1960`s in Korea, but all the artificial heart valves used are imported from abroad with very high costs until recent years. New artificial heart valves have been developed in Korea Advanced Institute of Science and Technology since early 1980`s. The first developed valve was designed with a free-floating pyrolytic carbon disk that is suspended in a titanium cage. The design of the valve was tested in vitro, and in animals in 1987. The results from this study was that the eccentrically placed struts creates a major and minor orifice when the disc opens and stagnation of flow in the area of the minor orifice has led to valve thrombosis. In this work, the design of the valve was changed from a single - leaflet valve to double - leaflet one in order to resolve the problems observed in the first - year tests. Morphological and hemodynamic studies were made for the newly designed valves through the in vitro and in vivo tests. The design and partial materials of the artificial heart valve was improved comparing with first - year`s model. The disc in the valve was modified from single - leaflet to bi - leaflet, and the material of the cage was changed from titanium metal to silicon - alloyed pyrolytic carbon. A test was made for the valve in order to examine its mechanical performance and stability. Morphological and hemodynamic studies were made for the valve that had been implanted in tricuspid position of mongrel dogs. All the test animals were observed just before the deaths. A new artificial heart valve was designed and fabricated in order to resolve the problems observed in the old model. The new valve was verified to have good stability and high resistance to wear through the performance tests. The hemodynamic properties of the valve after implantation were also estimated to be good in animal tests. Therefore, the results suggest that the newly designed valve in this work has a good quality in view of the biocompatibility. However, valve thrombosis on valve leaflets and annulus were found. This morphological findings were in accordance with results of surface polishing status studies, indicating that a technique of fine polishing of the surface is necessary to develop a valve with higher quality and performance.

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Sustained release of alginate hydrogel containing antimicrobial peptide Chol-37(F34-R) in vitro and its effect on wound healing in murine model of Pseudomonas aeruginosa infection

  • Shuaibing Shi;Hefan Dong;Xiaoyou Chen;Siqi Xu;Yue Song;Meiting Li;Zhiling Yan ;Xiaoli Wang ;Mingfu Niu ;Min Zhang;Chengshui Liao
    • Journal of Veterinary Science
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    • v.24 no.3
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    • pp.44.1-44.17
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    • 2023
  • Background: Antibiotic resistance is a significant public health concern around the globe. Antimicrobial peptides exhibit broad-spectrum and efficient antibacterial activity with an added advantage of low drug resistance. The higher water content and 3D network structure of the hydrogels are beneficial for maintaining antimicrobial peptide activity and help to prevent degradation. The antimicrobial peptide released from hydrogels also hasten the local wound healing by promoting epithelial tissue regeneration and granulation tissue formation. Objective: This study aimed at developing sodium alginate based hydrogel loaded with a novel antimicrobial peptide Chol-37(F34-R) and to investigate the characteristics in vitro and in vivo as an alternative antibacterial wound dressing to treat infectious wounds. Methods: Hydrogels were developed and optimized by varying the concentrations of crosslinkers and subjected to various characterization tests like cross-sectional morphology, swelling index, percent water contents, water retention ratio, drug release and antibacterial activity in vitro, and Pseudomonas aeruginosa infected wound mice model in vivo. Results: The results indicated that the hydrogel C proved superior in terms of cross-sectional morphology having uniformly sized interconnected pores, a good swelling index, with the capacity to retain a higher quantity of water. Furthermore, the optimized hydrogel has been found to exert a significant antimicrobial activity against bacteria and was also found to prevent bacterial infiltration into the wound site due to forming an impermeable barrier between the wound bed and external environment. The optimized hydrogel was found to significantly hasten skin regeneration in animal models when compared to other treatments in addition to strong inhibitory effect on the release of pro-inflammatory cytokines (interleukin-1β and tumor necrosis factor-α). Conclusions: Our results suggest that sodium alginate -based hydrogels loaded with Chol-37(F34-R) hold the potential to be used as an alternative to conventional antibiotics in treating infectious skin wounds.

Hemodynamic Evaluation of Acute Mitral Valve Insufficiency Model induced by Chordae Tendinae Rupture in Normal Dogs (개에서 건삭파열로 유발한 급성 이첨판 폐쇄부전 모델의 혈류역학적 평가)

  • Kim, Sehoon;Kim, Nam-Soo;Lee, Ki-Chang;Kim, Jong Min;Kim, Min-Su
    • Journal of Veterinary Clinics
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    • v.31 no.5
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    • pp.367-370
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    • 2014
  • The study was to observe hemodynamic alterations of cardiac function to design a model of canine mitral valve insufficiency (MVI) based on chordae tendinae rupture (CTR). Ten healthy beagles with normal heart function were used in this study. To measure hemodynamics, the patient monitor was equipped for invasive blood pressure and a Swan-Ganz catheter. Hemodynamic alterations were checked promptly during CTR procedures. MVI model was made by transection of the chordae tendinae with small arthroscopy hook knife through $5^{th}$ intercostal open chest. Color Doppler at the level of the mitral valve showed high-velocity regurgitant flow immediately after CTR at intraoperative echocardiography. In hemodynamic measurements, pulmonary capillary wedge pressure (PCWP) was significantly increased, while mean arterial pressure (MAP), venous pressure (VP), pulmonary arterial pressure (PAP), cardiac output (CO) and cardiac index (CI) were significantly decreased after CTR. It was known that the left atrium was overloaded by regurgitant volume from the left ventricle. In conclusion, the MVI model induced by CTR technique in this study should be used as suitable one for the effective research of canine mitral valve disease. Further study should be needed to measure the chronic alternation of mitral valve in the model.

Immunoregulatory Effects of Water Extracts of Scutellariae Radix in DSS-Induced Inflammatory Bowel Disease Animal Model (DSS로 유도된 염증성 장 질환 동물 모델에서 황금 열수 추출물이 면역 조절 기능에 미치는 영향)

  • Lee, Sun-Hee;Lim, Beong-Ou;Choue, Ryo-Won
    • Journal of Nutrition and Health
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    • v.37 no.6
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    • pp.431-439
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    • 2004
  • Scutellariae Radix (Scu.), one of the immune-regulatory substances, is recognized to play the role in the metabolic process of inflammation, allergy and immunity. It has been traditionally used in the Oriental medicine to treat inflammatory bowel diseases (IBD). The purpose of this study was to evaluate the effects of water extracts of Scutellariae Radix on the spleen lymphocyte immune function in the Balb/c female mice treated with dextran sodium sulfate (DSS) to induce colitis. Water extract of Scutellariae Radix (100 mg/kg) and sulfasalazine (50 mg/kg) were administrated orally for 2 weeks of experimental period. Mice were divided into three experimental groups randomly: DSS group (5% DSS was ad libitum for 5 days) as control group, DSS + Scu. (water extracts of Scutellariae Radix for 2 weeks after 5% DSS was ad libitum for 5 days) as experimental group, and DSS + Sulfasalazine group (Sulfasalazine for 2 weeks after 5% DSS was ad libitum for 5 days) as positive control group. Levels of Ig A, Ig E, CD4$^{+}$, CD8$^{+}$, TNF-$\alpha$ and other cytokines were measured. Treatment of DSS for 5 days induced bowel inflammation and the treatment with Scu. water exteract and sulfasalazine significantly recovered the damage. The length of intestine of DSS group was significantly shorter than that of other groups. The serum and fecal concentration of Ig A of SS + Scu group was higher than those of DSS group. The contents of CD4$^{+}$ T cells was higher in the DSS + Scu. group than the other groups and CD8$^{+}$ T cells was the lowest in DSS + Sulfasalazine group. The Ig A level of cultured supernatant of spleen lymphocyte was the highest, while the Ig E level was the lowest in SS + Scu group. The concentration of TNF-$\alpha$, cytokine secreted from the Th1 cell in the supernatant spleen lymphocyte, was the highest in the DSS group and the lowest in the DSS + Scu. group. The concentration of IFN-${\gamma}$ and ll...-12 was lower in the DSS + Scu. group than those of the other groups. The concentration of IL-4 in the supernatant of spleen lymphocyte was the lowest in the DSS + Scu. group but IL-10 was not significantly different. Based on these findings, water extract of Scutellariae Radix exhibited the inhibitory effect via IL-4 production thereby inhibited the production of Ig E and strengthened immune system, and alleviated injury in DSS- induced colitis mice model.

Restorative effects of Rg3-enriched Korean Red Ginseng and Persicaria tinctoria extract on oxazolone-induced ulcerative colitis in mice

  • Ullah, H.M. Arif;Saba, Evelyn;Lee, Yuan Yee;Hong, Seung-Bok;Hyun, Sun-Hee;Kwak, Yi-Seong;Park, Chae-Kyu;Kim, Sung Dae;Rhee, Man Hee
    • Journal of Ginseng Research
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    • v.46 no.5
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    • pp.628-635
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    • 2022
  • Background: Ulcerative colitis (UC) is the large intestine disease that results in chronic inflammation and ulcers in the colon. Rg3-enriched Korean Red Ginseng extract (Rg3-RGE) is known for its pharmacological activities. Persicaria tinctoria (PT) is also used in the treatment of various inflammatory diseases. The aim of this study is to investigate the attenuating effects of Rg3-RGE with PT on oxazolone (OXA)-induced UC in mice. Methods: A total of six groups of mice including control group, OXA (as model group, 1.5%) group, sulfasalazine (75 mg/kg) group, Rg3-RGE (20 mg/kg) group, PT (300 mg/kg) group, and Rg3-RGE (10 mg/kg) with PT (150 mg/kg) group. Data on the colon length, body weight, disease activity index (DAI), histological changes, nitric oxide (NO) assay, Real-time PCR of inflammatory factors, ELISA of inflammatory factors, Western blot, and flow cytometry analysis were obtained. Results: Overall, the combination treatment of Rg3-RGE and PT significantly improved the colon length and body weight and decreased the DAI in mice compared with the treatment with OXA. Additionally, the histological injury was also reduced by the combination treatment. Moreover, the NO production level and inflammatory mediators and cytokines were significantly downregulated in the Rg3-RGE with the PT group compared with the model group. Also, NLR family pyrin domain containing 3 (NLRP3) inflammasome and nuclear factor kappa B (NF-𝛋B) were suppressed in the combination treatment group compared with the OXA group. Furthermore, the number of immune cell subtypes of CD4+ T-helper cells, CD19+ B-cells, and CD4+ and CD25+ regulatory T-cells (Tregs) was improved in the Rg3-RGE with the PT group compared with the OXA group. Conclusion: Overall, the mixture of Rg3-RGE and PT is an effective therapeutic treatment for UC.

Triptolide Mimics the Effect of Dietary Restriction on Lifespan and Retards Age-related Diseases in Caenorhabditis elegans (트립톨라이드가 식이제한에 의한 수명연장과 노화관련 질환에 미치는 영향)

  • Beak, Sun-Mi;Park, Sang-Kyu
    • Journal of Life Science
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    • v.28 no.8
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    • pp.931-937
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    • 2018
  • Triptolide is a compound found in Tripterygium wilfordii and reported to have an anti-inflammatory and anti-oxidant activities. A previous study shows that the dietary supplementation with triptolide increases resistance to environmental stressors, including oxidative stress, heat shock, and ultraviolet irradiation, and extends lifespan in C. elegans. Here, we investigated the underlying mechanisms involved in the lifespan-extending effect of triptolide. The effect of triptolide on age-related diseases, such as diabetes mellitus and Alzheimer's disease, was also examined using animal disease models. The longevity phenotype conferred by triptolide was not observed in the eat-2 mutant, a well-known genetic model of dietary restriction, while there was an additional lifespan extension with triptolide in age-1 and clk-1 mutants. The long lifespan of age-1 mutant is resulted from a reduced insulin/IGF-1-like signaling and the clk-1 mutant lives longer than wild-type due to dysfunction of mitochondrial electron transport chain reaction. The effect of dietary restriction using bacterial dilution on lifespan also overlapped with that of triptolide. The toxicity of high glucose diet or transgenic human amyloid beta gene was significantly suppressed by the supplementation with triptolide. These findings suggest that triptolide can mimic the effect of dietary restriction on lifespan and onset of age-related diseases. We conclude that triptolide can be a strong candidate for the development of dietary restriction mimetics.

Tissue Distribution of HuR Protein in Crohn's Disease and IBD Experimental Model (염증성 장질환 모델 및 크론병 환자에서의 점막상피 HuR 단백질의 변화 분석)

  • Choi, Hye Jin;Park, Jae-Hong;Park, Jiyeon;Kim, Juil;Park, Seong-Hwan;Oh, Chang Gyu;Do, Kee Hun;Song, Bo Gyoung;Lee, Seung Joon;Moon, Yuseok
    • Journal of Life Science
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    • v.24 no.12
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    • pp.1339-1344
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    • 2014
  • Inflammatory bowel disease is an immune disorder associated with chronic mucosal inflammation and severe ulceration in the gastrointestinal tract. Antibodies against proinflammatory cytokines, including TNF${\alpha}$, are currently used as promising therapeutic agents against the disease. Stabilization of the transcript is a crucial post-transcriptional process in the expression of proinflammatory cytokines. In the present study, we assessed the expression and histological distribution of the HuR protein, an important transcript stabilizer, in tissues from experimental animals and patients with Crohn's disease. The total and cytosolic levels of the HuR protein were enhanced in the intestinal epithelia from dextran sodium sulfate (DSS)-treated mice compared to those in control tissues from normal mice. Moreover, the expression of HuR was very high only in the mucosal and glandular epithelium, and the relative localization of the protein was sequestered in the lower parts of the villus during the DSS insult. The expression of HuR was significantly higher in mucosal lesions than in normal-looking areas. Consistent with the data from the animal model, the expression of HuR was confined to the mucosal and glandular epithelium. These results suggest that HuR may contribute to the post-transcriptional regulation of proinflammatory genes during early mucosal insults. More mechanistic investigations are warranted to determine the potential use of HuR as a predictive biomarker or a promising target against IBD.