• Title/Summary/Keyword: agent model

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Silymarin's Protective Effects and Possible Mechanisms on Alcoholic Fatty Liver for Rats

  • Zhang, Wei;Hong, Rutao;Tian, Tulei
    • Biomolecules & Therapeutics
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    • v.21 no.4
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    • pp.264-269
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    • 2013
  • Silymarin has been introduced fairly recently as a hepatoprotective agent. But its mechanisms of action still have not been well established. The aim of this study was to make alcoholic fatty liver model of rats in a short time and investigate silymarin's protective effects and possible mechanisms on alcoholic fatty liver for rats. The model of rat's alcoholic fatty liver was induced by intragastric infusion of ethanol and high-fat diet for six weeks. Histopathological changes were assessed by hematoxylin and eosin staining (HE). The activities of alanine transarninase (ALT) and aspartate aminotransferase (AST), the levels of total bilirubin (TBIL), total cholesterol (TC) and triglyceride (TG) in serum were detected with routine laboratory methods using an autoanalyzer. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) and the level of malondialdehyde (MDA) in liver homogenates were measured by spectrophotometry. The TG content in liver tissue was determined by spectrophotometry. The expression of nuclear factor-${\kappa}B$ (NF-${\kappa}B$), intercellular adhesion molecule-1 (ICAM-1) and interleukin-6 (IL-6) in the liver were analyzed by immunohistochemistry. Silymarin effectively protected liver from alcohol-induced injury as evidenced by improving histological damage situation, reducing ALT and AST activities and TBIL level in serum, increasing SOD and GPx activities and decreasing MDA content in liver homogenates and reducing TG content in liver tissue. Additionally, silymarin markedly downregulated the expression of NF-${\kappa}B$ p65, ICAM-1 and IL-6 in liver tissue. In conclusion, Silymarin could protect against the liver injury caused by ethanol administration. The effect may be related to alleviating lipid peroxidation and inhibiting the expression of NF-${\kappa}B$.

Alcohol Induced Hepatic Fibrosis in Pig

  • Lee, Chang-Woo;Lee, Cha-Soo;Jeong, Won-Il;Do, Sun-Hee;Noh, Dong-Hyung;Jeong, Kyu-Shik
    • Proceedings of the Korean Society of Veterinary Pathology Conference
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    • 2002.11a
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    • pp.146-146
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    • 2002
  • Hepatic disease has been noted and reported for involvement various detrimental factors. Among many detrimental injury factors, alcohol has been noted for hepatitis, fatty liver, fibrosis, and hepatic cirrhosis. The purpose of this study is to develop animal model for hepatic fibrosis in pig with ethanol, and to search new anti-fibrogenic agent. Twelve male Landrace pigs were divided into 3 groups of 4 animals each. Group 1, 2 and 3 were fed with ceramic water only, ceramic water + liquid diet containing 20% ethanol and normal tap water + containing 20% ethanol for 12 weeks, respectively. At week 12, all pigs were immediately sacrificed for collection each tissue and blood. Serologically, serum ALT and AST levels were significantly reversed in group 2, comparing to group 3. They were normal range in pigs of group 1. Microscopically, macrovesicular lipid droplets and moderate necrosis were evident in the tap water + ethanol fed group 3. However, ceramic water intake group 1 showed normal. Moreover, in group 3, little fatty changes and mild necrosis were observed. Collagen fibers were detected in the spaces of surrounding periportal and interlobular areas in the group 3 of tap water + ethanol, but collagen synthesis and its thickness of fibrotic septa connecting portal tracts was markedly reduced in the group 2 of ceramic water + ethanol. In immunohistochemistry, myofibroblasts were detected in the ethanol and tap water treated group 3. No or a few myofibroblasts were observed in groups 1 and 2. CYP 2E1 was rarely detected in group 1 fed ceramic water. However, group 2 showed slightly activation of CYP 2E1 in the area of pericentral, while CYP 2E1 was significantly activated in group 3 fed tap and ethanol. Taken together above, alcohol fibrosis model in pig was established. Furthermore, ceramic water had an inhibitory and protecting ability for alcohol-induced hepatic damages.

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Neuroprotective Effects of Ginkgo biloba extract, GBB, in the Transient Ischemic Rat Model

  • Oh, Jin-Kyung;Jung, Ji-Wook;Oh, Hye-Rim;Han, Yong-Nam;Ryu, Jong-Hoon
    • Biomolecules & Therapeutics
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    • v.15 no.3
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    • pp.169-174
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    • 2007
  • In the present study, we investigated the neuroprotective effects of standardized Ginkgo biloba extract (GBB) (total terpene trilactones, 13 ${\pm}$ 3%; biflavone, 4.5 ${\pm}$ 1.5%; flavonol glycoside, < 8%; proanthocyanidine, under detection limit) on ischemia-reperfusion-induced brain injury in the rats. Ischemia was induced by the intraluminal occlusion of the right middle cerebral artery for 2 h and reperfusion was continued for 22 h. GBB was orally administered, promptly prior to reperfusion and 2 h after. Total infarction volume in the ipsilateral hemispheres of ischemia-reperfusion rats were significantly reduced by treatment with GBB in a dose-dependent manner (P<0.05). The therapeutic time window of GBB was 3 h in this ischemia-reperfusion rat model. Furthermore, GBB also significantly inhibited increased neutrophil infiltration of ischemic brain tissue, as estimated by myeloperoxidase activity. These findings suggest that GBB plays a crucial protective role in ischemia-induced brain injury, in part, via inhibition of neutrophil infiltration, and suggest that this GBB could serve as a neuroprotective agent following transient focal ischemic brain injury.

Palmitoylpolysaccharide-coated Liposomes As A Potential Oral Drug Carrier (경구용 약물수송체로서의 팔미토일 치환 다당체로 코팅된 리포좀)

  • Hahn, Yang-Hee;Yi, Jung-Woo;Choi, Young-Wook
    • Journal of Pharmaceutical Investigation
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    • v.24 no.2
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    • pp.73-83
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    • 1994
  • Applications of liposomes as a drug carrier for the oral delivery of poorly-absorbable macromolecular drugs have been limited, because of their instability in gastrointestinal environments including pH, bile salts, and digestive enzymes. Two polysaccharides, dextran(DX) and pullulan(PL), were introduced to the preformed liposomes in order to enhance the stability. Palmitoyl derivatives of polysaccharides, palmitoyldextran(PalDX) and palmitoylpullulan(PalPL), were synthesizd and introduced to the liposomes during preparation for the same purpose of stability. The effects of these polysaccharides coating were evaluated basically by physical properties of particle size distribution and optical microscopy, then compared with uncoated liposomes by the observations of both in vitro stability and in vovo absorption characteristics. The geometric mean diameters of polysaccharide-coated liposomes were greater than that of uncoated liposome, showing the outermost polysaccharide-coated layer under the optical microscopy. In vitro stabilities of uncoated or polysaccharides-coated liposomes were measured by turbidity changes in various pH buffer solutions containing sodium choleate as bile salts. While uncoated liposome was very sensitive to bile salts, polysaccharides-coated liposomes were stable in relatively higher concentrations of sodium choleate, giving the results of better stability of PalDX- and PalPL-coated liposomes than that of DX- and PL-coated liposomes. After liposomal encapsulation of acyclovir(ACV), an antiviral agent as a model drug, it has been administered orally to rats as dose of ACV 40 mg/kg. Plasma concentrations of ACV were assayed by HPLC and analyzed by model-independent pharmacokinetics. Pharmacokinetic parameters of Cmax, tmax, and [AUC] have been compared.

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Preparation and Evaluation of PGE1-ethyl Ester Intraurethral Solutions for Erectile Dysfunction (PGE1-ethyl Ester함유 발기부전 치료용 요도주입 액제의 제조 및 평가)

  • Choi, Han-Gon;Yoo, Bon-Kyu;Rhee, Jong-Dal;Kim, Jung-Ae;Kwon, Tae-Hyub;Woo, Jong-Soo;Yong, Chul-Soon
    • Journal of Pharmaceutical Investigation
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    • v.36 no.4
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    • pp.223-229
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    • 2006
  • [ $PGE_1$ ]-ethyl ester intraurethral solutions were prepared in ethanol/propylene glycol mixture with penetration enhancer and viscosity-enhancing agent. The stability of $PGE_1$-ethyl ester in intraurethral solution was investigated at various temperature. Simultaneous determination of $PGE_1$-ethyl ester and $PGE_1$ was performed using a validated HPLC technique. In pentobarbital anesthetized cats, increase in intracavernous pressure(ICP), increase in penile length and duration of erectile response were determined after intraurethral application of $PGE_1$-ethyl ester solutions. $PGE_1$-ethyl ester solutions, when instilled into the eyes of rabbits, produces no noticeable irritation, or slight transient conjunctival irritation. From these results, ocular irritation of this solutions was judged as practically non-irritating. The stability study indicates that the therapeutically effective content in solution is well maintained for 46 weeks or longer when they are stored at $4^{\circ}C$. After intraurethral application of $PGE_1$-ethyl ester, ICP was increased and penile erection was induced. $PGE_1$-ethyl ester intraurethral solutions for erectile dysfunction could be developed and evaluated by employing feline erection model.

IMMUNOHISTOCHEMICAL STUDY OF THE VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) EXPRESSION IN GENISTEIN TREATED HAMSTER BUCCAL POUCH ORAL CARCINOMA MODEL (Genistein을 투여한 햄스터 협낭 구강암 모델에서의 Vascular Endothelial Growth Factor (VEGF) 발현 변화에 대한 면역조직화학적 연구)

  • Myoung, Hoon;Kim, Young-Yun;Choi, Sang-Mook;Chung, Chong-Pyoung;Kim, Myung-Jin
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.28 no.2
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    • pp.147-154
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    • 2002
  • Genistein that is a component of soy has been reported to have a protective effect on the carcinogenesis of various tumors and to inhibit the growth of a wide variety of tumor cell in vitro. Angiogenesis is an essential process for the carcinogenesis, growth, invasion and metastasis of cancer and genistein has been suggested to act as natural anti-angiogenic agent. The purpose of this study was to evaluate the effects of genistein on the vascular endothelial growth factor (VEGF) expression in hamster buccal pouch oral carcinogenesis model induced by 9, 10-dimethyl 1,2-benzanthracene (DMBA). Experimental group that were supplied with 0.1mg/day genistein were sacrificed by time schedules and routinely processed for immunohistochemical examination of VEGF. In genistein treated group, carcinogenesis was retarded with respect to the acanthosis, hyperkeratosis, and epithelial dysplasia. Immunohistochemical study showed that the VEGF protein of genistein group was less expressed than that of the control group. (p<0.05) Thus, it is postulated that genistein has chemopreventive effect on the oral carcinogenesis, and this chemopreventive effect, at least partly, is originated from the anti-angiogenic effect of genistein

Effects of Traditional Chinese Herbal Medicine Shengmai-San and Pyungwi-San on Gastrointestinal Motility in Mice (생맥산 및 평위산 추출물의 위장관 운동 조절 효능에 관한 연구)

  • Lee, Min Cheol;Park, Jin Ryeong;Shim, Ji Hwan;Ahn, Tae Seok;Kim, Byung Joo
    • Journal of Korean Medicine for Obesity Research
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    • v.15 no.2
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    • pp.68-74
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    • 2015
  • Objectives: The purpose of this study was to investigate the effects of Shengmai-san and Pyungwi-san, a herbal product used in traditional Chinese medicine, on gastrointestinal (GI) motility in mice. Methods: The in vivo effects of Shengmai-san and Pyungwi-san on GI motility were investigated by measuring the intestinal transit rates (ITRs) using Evans blue in normal mice and in mice with experimentally induced GI motility dysfunction (GMD). GMD was induced by injecting acetic acid or streptozotocin intraperitoneally. Results: In normal Institute of Cancer Research mice, ITRs were significantly and dose-dependently increased by Shengmaisan (0.01~1 g/kg) and Pyungwi-san (0.01~1 g/kg). The ITRs of acetic acid induced peritoneal irritation model and streptozotocin-induced diabetic model mice were significantly reduced compared to normal mice, and these reductions were significantly and dose-dependently inhibited by Shengmai-san (0.01~1 g/kg) and Pyungwi-san (0.01~1 g/kg). Conclusions: These results suggest that both Shengmai-san and Pyungwi-san are a good candidate for the development of a prokinetic agent that may prevent or alleviate GMD.

An 8-wk, randomized, double-blind, placebo-controlled clinical trial for the antidiabetic effects of hydrolyzed ginseng extract

  • Park, Soo-Hyun;Oh, Mi-Ra;Choi, Eun-Kyung;Kim, Min-Gul;Ha, Ki-Chan;Lee, Seung-Kwon;Kim, Young-Gon;Park, Byung-Hyun;Kim, Dal-Sik;Chae, Soo-Wan
    • Journal of Ginseng Research
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    • v.38 no.4
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    • pp.239-243
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    • 2014
  • Background: To investigate the antidiabetic effects of hydrolyzed ginseng extract (HGE) for Korean participants in an 8-wk, randomized, double-blinded, placebo-controlled clinical trial. Methods: Impaired fasting glucose participants [fasting plasma glucose (FPG) ${\geq}5.6mM$ or < 6.9mM who had not been diagnosed with any disease and met the inclusion criteria were recruited for this study. The 23 participants were randomly divided into either the HGE (n = 12, 960 mg/d) or placebo (n = 11) group. Outcomes included measurements of efficacy (FPG, postprandial glucose, fasting plasma insulin, postprandial insulin, homeostatic model assessment-insulin resistance, and homeostatic model assessment-${\beta}$) and safety (adverse events, laboratory tests, electrocardiogram, and vital signs). Results: After 8 wk of HGE supplementation, FPG and postprandial glucose were significantly decreased in the HGE group compared to the placebo group. No clinically significant changes in any safety parameter were observed. Our study revealed that HGE is a potent antidiabetic agent that does not produce noticeable adverse effects. Conclusion: HGE supplementation may be effective for treating impaired fasting glucose individuals.

Antidepressant effects of ginsenoside Rf on behavioral change in the glial degeneration model of depression by reversing glial loss

  • Kim, Yunna;Lee, Hwa-Young;Choi, Yu-Jin;Cho, Seung-Hun
    • Journal of Ginseng Research
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    • v.44 no.4
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    • pp.603-610
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    • 2020
  • Background: Depression is a common neuropsychiatric disease that shows astrocyte pathology. Ginsenoside Rf (G-Rf) is a saponin found in Panax ginseng which has been used to treat neuropsychiatric diseases. We aimed to investigate antidepressant properties of G-Rf when introduced into the L-alphaaminoadipic acid (L-AAA)-infused mice model which is representative of a major depressive disorder that features diminished astrocytes in the brain. Methods: L-AAA was infused into the prefrontal cortex (PFC) of mice to induce decrease of astrocytes. Mice were orally administered G-Rf (20 mg/kg) as well as vehicle only or imipramine (20 mg/kg) as controls. Depression-like behavior of mice was evaluated using forced swimming test (FST) and tail suspension test (TST). We observed recovery of astroglial impairment and increased proliferative cells in the PFC and its accompanied change in the hippocampus by Western blot and immunohistochemistry to assess the effect of G-Rf. Results: After injection of L-AAA into the PFC, mice showed increased immobility time in FST and TST and loss of astrocytes without significant neuronal change in the PFC. G-Rf-treated mice displayed significantly more decreased immobility time in FST and TST than did vehicle-treated mice, and their immobility time almost recovered to those of the sham mice and imipramine-treated mice. G-Rf upregulated glial fibrillary acidic protein (GFAP) expression and Ki-67 expression in the PFC reduced by L-AAA and also alleviated astroglial change in the hippocampus. Conclusion: G-Rf markedly reversed depression-like behavioral changes and exhibited protective effect against the astrocyte ablation in the PFC induced by L-AAA. These protective properties suggest that G-Rf might be a therapeutic agent for major depressive disorders.

Improvement of Environment Recognition using Multimodal Signal (멀티 신호를 이용한 환경 인식 성능 개선)

  • Park, Jun-Qyu;Baek, Seong-Joon
    • The Journal of the Korea Contents Association
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    • v.10 no.12
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    • pp.27-33
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    • 2010
  • In this study, we conducted the classification experiments with GMM (Gaussian Mixture Model) from combining the extracted features by using microphone, Gyro sensor and Acceleration sensor in 9 different environment types. Existing studies of Context Aware wanted to recognize the Environment situation mainly using the Environment sound data with microphone, but there was limitation of reflecting recognition owing to structural characteristics of Environment sound which are composed of various noises combination. Hence we proposed the additional application methods which added Gyro sensor and Acceleration sensor data in order to reflect recognition agent's movement feature. According to the experimental results, the method combining Acceleration sensor data with the data of existing Environment sound feature improves the recognition performance by more than 5%, when compared with existing methods of getting only Environment sound feature data from the Microphone.