• Title/Summary/Keyword: In Vivo and In Vitro Function

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Effects of Water Extract of Smoke-dried Skipjack Tuna on Memory in a Scopolamine-induced Amnesia Animal Model

  • Lim, Soon-Sung;Hwang, In-Koo;Yoo, Ki-Yeon;Kang, Il-Jun;Shin, Hyun-Kyung;Kim, Sang-Moo;Won, Moo-Ho
    • Food Science and Biotechnology
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    • v.17 no.3
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    • pp.594-597
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    • 2008
  • Natural products have been used to treat many neurological illnesses such as Alzheimer's disease. In the present study, the effects of the water extract of smoke-dried skipjack tuna (WSST), which is used as a traditional seasoning in Japan, as well as its fractions on acetylcholinesterase (AChE) inhibition in vitro and on memory in scopolamine-induced amnesia mice in vivo were evaluated. Bio-Rad P-2 gel permeation chromatography revealed the presence of 7 peaks and AChE significantly inhibited peak 3 and 5. When in vivo behavioral studies were conducted, a passive avoidance test revealed that treatment with 50 and 100 mg/kg WSST as well as with fraction 3 and 5 improved the loss in memory retention induced by scopolamine. These results suggest that skipjack tuna extract and its fractions improve memory deficits and that these substances are suitable for use in healthy foods designed to improve memory deficits induced by aging and Alzheimer's disease.

High fat diet-induced brain damaging effects through autophagy-mediated senescence, inflammation and apoptosis mitigated by ginsenoside F1-enhanced mixture

  • Hou, Jingang;Jeon, Byeongmin;Baek, Jongin;Yun, Yeejin;Kim, Daeun;Chang, Boyoon;Kim, Sungyeon;Kim, Sunchang
    • Journal of Ginseng Research
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    • v.46 no.1
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    • pp.79-90
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    • 2022
  • Background: Herbal medicines are popular approaches to capably prevent and treat obesity and its related diseases. Excessive exposure to dietary lipids causes oxidative stress and inflammation, which possibly induces cellular senescence and contribute the damaging effects in brain. The potential roles of selective enhanced ginsenoside in regulating high fat diet (HFD)-induced brain damage remain unknown. Methods: The protection function of Ginsenoside F1-enhanced mixture (SGB121) was evaluated by in vivo and in vitro experiments. Human primary astrocytes and SH-SY5Y cells were treated with palmitic acid conjugated Bovine Serum Albumin, and the effects of SGB121 were determined by MTT and lipid uptake assays. For in vivo tests, C57BL/6J mice were fed with high fat diet for 3 months with or without SGB121 administration. Thereafter, immunohistochemistry, western blot, PCR and ELISA assays were conducted with brain tissues. Results and conclusion: SGB121 selectively suppressed HFD-induced oxidative stress and cellular senescence in brain, and reduced subsequent inflammation responses manifested by abrogated secretion of IL-6, IL-1β and TNFα via NF-κB signaling pathway. Interestingly, SGB121 protects against HFD-induced damage by improving mitophagy and endoplasmic reticulum-stress associated autophagy flux and inhibiting apoptosis. In addition, SGB121 regulates lipid uptake and accumulation by FATP4 and PPARα. SGB121 significantly abates excessively phosphorylated tau protein in the cortex and GFAP activation in corpus callosum. Together, our results suggest that SGB121 is able to favor the resistance of brain to HFD-induced damage, therefore provide explicit evidence of the potential to be a functional food.

Effect of Lactobacillus fermentum MG590 on Alcohol Metabolism and Liver Function in Rats

  • Kim, Ji-Hyun;Kim, Hyun-Jin;Son, Jeong-Hwa;Chun, Ho-Nam;Yang, Jin-Oh;Choi, Sung-Jin;Paek, Nam-Soo;Choi, Gyoung-Hoon;Kim, Sung-Koo
    • Journal of Microbiology and Biotechnology
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    • v.13 no.6
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    • pp.919-925
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    • 2003
  • Alcohol consumption has numerous health consequences for the human body. For example, heavy drinking on a daily basis causes liver diseases, and certain products such as acetaldehyde produced from alcohol metabolism are more toxic than alcohol itself. Accordingly, the current study evaluated the role of Lactobacillus fermentum MG590 to enhance the removal of the toxic effect of alcohol in alcohol metabolism. The maximum activities of the alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) by L. fermentum MG590 were observed after 6 h of culture. The production of ADH and ALDH by L. fermentum MG590 was also confirmed by SDS-PAGE. Six hours after the addition of alcohol to a culture broth of L. fermentum MG590, the alcohol concentration decreased from 7.5 to 2.7%. From an in vitro evaluation based on hepatocytes, the viability of hepatocytes in a medium containing alcohol and the cytosol of L. fermentum MG590 was higher than that in a medium containing only alcohol. From an in vivo test using SD rats fed a 22% alcoholic drink, the blood alcohol concentration (BAC), glutamic-oxaloacetic transaminase (GOT), and glutamic-pyruvic transaminase (GPT) in the rats fed a medium containing L. fermentum MG590 were lower than those in the rats fed a medium containing only the alcohol drink. These results demonstrate that the ADH and ALDH produced by L. fermentum MG590 play an important role in detoxicating alcohol in vivo. Therefore, a fermentation broth of L. fermentum MG590 could be used as an effective alcohol detoxification drink.

A Review of the Neuroprotective Effects of Cinnamon in Experimental Studies on Parkinson's Disease (파킨슨병 관련 실험 연구에서 육계의 신경 보호효과에 대한 고찰)

  • Heo, Hyemin;Han, Juhee;Jeong, Minjeong;Kim, Hongjun;Jang, Insoo
    • The Journal of Internal Korean Medicine
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    • v.41 no.6
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    • pp.1089-1099
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    • 2020
  • Objective: The purpose of this study was to investigate the effect of cinnamon on the treatment of Parkinson's disease (PD) and to introduce its use in Korea. Method: We searched the experimental studies in electronic databases (PubMed, CNKI, Wanfang, CiNii, J-STAGE, Science ON, and OASIS) using the key search terms "cinnamic acid", "cinnamon", "cinnamomum", "Parkinson's disease", "Parkinson disease", "Parkinsonism", and "dopamine". This study only involved experimental studies (in vivo and in vitro) that adopted cinnamon as a single administration and measured indicators relating to Parkinson's disease, including parkin, tyrosine hydroxylase (TH), and dopamine. Results: A Total of 11 literature studies were selected, and they all showed that treatment with cinnamon has a neuroprotective effect. Cinnamon activated neuroprotective factors and restored neurotransmitters and it reduced the rate of oxidative stress and inflammation in neurons. As a result, cell viability was upregulated, while cell apoptosis and neurodegeneration were downregulated. Five in vivo studies, through behavioral tests, also confirmed that cinnamon recovers locomotor function in PD models. Conclusion: We identified that cinnamon is an effective neural protector and improves motor performance in behavioral testing in the experimental PD studies.

Ginsenoside Rp1 Exerts Anti-inflammatory Effects via Activation of Dendritic Cells and Regulatory T Cells

  • Bae, Jin-Gyu;Koo, Ji-Hye;Kim, Soo-Chan;Park, Tae-Yoon;Kim, Mi-Yeon
    • Journal of Ginseng Research
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    • v.36 no.4
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    • pp.375-382
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    • 2012
  • Ginsenoside Rp1 (G-Rp1) is a saponin derivate that provides anti-metastatic activities through inhibition of the NF-${\kappa}B$ pathway. In this study, we examined the effects of G-Rp1 on regulatory T cell (Treg) activation. After treatment of splenocytes with G-Rp1, Tregs exhibited upregulation of IL-10 expression, and along with dendritic cells (DCs), these Tregs showed increased cell number compared to other cell populations. The effect of G-Rp1 on Treg number was augmented in the presence of lipopolysaccharide (LPS), which mimics pathological changes that occur during inflammation. However, depletion of DCs prevented the increase in Treg number in the presence of G-Rp1 and/or LPS. In addition, G-Rp1 promoted the differentiation of the memory types of $CD4^+Foxp3^+CD62L^{low}$ Tregs rather than the generation of new Tregs. In vivo experiments also demonstrated that Tregs and DCs from mice that were fed G-Rp1 for 7 d and then injected with LPS exhibited increased activation compared with those from mice that were injected with LPS alone. Expression of TGF-${\beta}$ and CTLA4 in Tregs was increased, and upregulation of IL-2 and CD80/CD86 expression by DCs affected the suppressive function of Tregs through IL-2 receptors and CTLA4. These data demonstrate that G-Rp1 exerts anti-inflammatory effects by activating Tregs in vitro and in vivo.

Effects of gas signaling molecule SO2 in cardiac functions of hyperthyroid rats

  • Qi Yang;Ting Yang;Xing Liu;Shengquan Liu;Wei Liu;Liangui Nie;Chun Chu;Jun Yang
    • The Korean Journal of Physiology and Pharmacology
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    • v.28 no.2
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    • pp.129-143
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    • 2024
  • Sulfur dioxide (SO2), a novel endogenous gas signaling molecule, is involved in the regulation of cardiac function. Exerting a key role in progression of hyperthyroidism-induced cardiomyopathy (HTC), myocardial fibrosis is mainly caused by myocardial apoptosis, leading to poor treatment outcomes and prognoses. This study aimed to investigate the effect of SO2 on the hyperthyroidism-induced myocardial fibrosis and the underlying regulatory mechanisms. Elisa, Masson staining, Western-Blot, transmission electron microscope, and immunofluorescence were employed to evaluate the myocardial interstitial collagen deposition, endoplasmic reticulum stress (ERS), apoptosis, changes in endogenous SO2, and Hippo pathways from in vitro and in vivo experiments. The study results indicated that the hyperthyroidism-induced myocardial fibrosis was accompanied by decreased cardiac function, and down-regulated ERS, apoptosis, and endogenous SO2-producing enzyme aspartate aminotransferase (AAT)1/2 in cardiac myocytes. In contrast, exogenous SO2 donors improved cardiac function, reduced myocardial interstitial collagen deposition, up-regulated AAT1/2, antagonized ERS and apoptosis, and inhibited excessive activation of Hippo pathway in hyperthyroid rats. In conclusion, the results herein suggested that SO2 inhibited the overactivation of the Hippo pathway, antagonized ERS and apoptosis, and alleviated myocardial fibrosis in hyperthyroid rats. Therefore, this study was expected to identify intervention targets and new strategies for prevention and treatment of HTC.

The effects of Korean Red Ginseng-derived components on oligodendrocyte lineage cells: Distinct facilitatory roles of the non-saponin and saponin fractions, and Rb1, in proliferation, differentiation and myelination

  • Lee, Ahreum;Kwon, Oh Wook;Jung, Kwi Ryun;Song, Gyun Jee;Yang, Hyun-Jeong
    • Journal of Ginseng Research
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    • v.46 no.1
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    • pp.104-114
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    • 2022
  • Background: Abnormalities of myelin, which increases the efficiency of action potential conduction, are found in neurological disorders. Korean Red Ginseng (KRG) demonstrates therapeutic efficacy against some of these conditions, however effects on oligodendrocyte (OL)s are not well known. Here, we examined the effects of KRG-derived components on development and protection of OL-lineage cells. Methods: Primary OL precursor cell (OPC) cultures were prepared from neonatal mouse cortex. The protective efficacies of the KRG components were examined against inhibitors of mitochondrial respiratory chain activity. For in vivo function of Rb1 on myelination, after 10 days of oral gavage into adult male mice, forebrains were collected. OPC proliferation were assessed by BrdU incorporation, and differentiation and myelination were examined by qPCR, western blot and immunocytochemistry. Results: The non-saponin promoted OPC proliferation, while the saponin promoted differentiation. Both processes were mediated by AKT and extracellular regulated kinase (ERK) signaling. KRG extract, the saponin and non-saponin protected OPCs against oxidative stress, and both KRG extract and the saponin significantly increased the expression of the antioxidant enzyme. Among 11 major ginsenosides tested, Rb1 significantly increased OL membrane size in vitro. Moreover, Rb1 significantly increased myelin formation in adult mouse brain. Conclusion: All KRG components prevented OPC deaths under oxidative stress. While non-saponin promoted proliferation, saponin fraction increased differentiation and OL membrane size. Furthermore, among all the tested ginsenosides, Rb1 showed the biggest increase in the membrane size and significantly enhanced myelination in vivo. These results imply therapeutic potentials of KRG and Rb1 for myelin-related disorders.

RalA-binding Protein 1 is an Important Regulator of Tumor Angiogenesis (Tumor angiogenesis에 있어서 RLIP76의 중요성)

  • Lee, Seunghyung
    • Journal of Life Science
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    • v.24 no.5
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    • pp.588-593
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    • 2014
  • Tumor angiogenesis is important in tumorigenesis and therapeutic interventions in cancer. To know inhibitor and effector of tumor angiogenesis in cancer, the specific gene of tumor and angiogenesis may develop the mechanisms of cancer suppression and therapy. Recently, we described the role of RalA-binding protein 1 (RLIP76) in tumor angiogenesis. Tumor vascular volumes were diminished, and vessels were fewer in number, shorter, and narrower in RLIP76 knockout mice than in wild-type mice. Moreover, angiogenesis in basement membrane matrix plugs was blunted in the knockout mice in the absence of tumor cells, with endothelial cells isolated from the lungs of these animals exhibiting defects in migration, proliferation, and cord formation in vitro. RLIP76 is expressed in most human tissues and is overexpressed in many tumor types. In addition, the protein regulates tumorigenesis and angiogenesis in vivo and in vitro. As the export of chemotherapy agents is a prominent cellular function of RLIP76, it is a major factor in mechanisms of drug resistance. Moreover, RLIP76 acts as a selective effector of the small GTPase, R-Ras, and regulates R-Ras signaling, leading to cell spreading and migration. Furthermore, in skin carcinogenesis, RLIP76 knockout mice are resistant, with tumors that form showing diminished angiogenesis. Thus, RLIP76 is required for efficient endothelial cell function and angiogenesis in solid tumors.

P-Glycoprotein-Based Drug-Drug Interactions: Preclinical Methods and Relevance to Clinical Observations

  • Aszalos, Adorjan
    • Archives of Pharmacal Research
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    • v.27 no.2
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    • pp.127-135
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    • 2004
  • Multiple drug administration is common in elderly, HIV, and cancer patients. Such treatments may result in drug-drug interactions due to interference at the metabolic enzyme level, and due to modulation of transporter protein functions. Both kinds of interference may result in altered drug distribution and toxicity in the human body. In this review, we have dealt with drug-drug interactions related to the most studied human transporter, P-glycoprotein. This transporter is constitutively expressed in several sites in the human body. Its function can be studied in vitro with different cell lines expressing P-glycoprotein in experiments using methods and equipment such as flow cytometry, cell proliferation, cell-free ATP as activity determination and Transwell culture equipment. In vivo experiments can be carried out by mdr1a(-/-) animals and by noninvasive methods such as NMR spectrometry. Some examples are also given for determination of possible drug-drug interactions using the above-mentioned cell lines and methods. Such preclinical studies may influence decisions concerning the fate of new drug candidates and their possible dosages. Some examples of toxicities obtained in clinics and summarized in this review indicate careful consideration in cases of polypharmacy and the requirement of preclinical studies in drug development activities.

Development of a Dynamic System Simulating Pig Gastric Digestion

  • Chiang, C.-C.;Croom, J.;Chuang, S.-T.;Chiou, P.W.S.;Yu, B.
    • Asian-Australasian Journal of Animal Sciences
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    • v.21 no.10
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    • pp.1522-1528
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    • 2008
  • The objective of this study was to develop a model for simulating gastric digestion in the pig. The model was constructed to include the chemical and physical changes associated with gastric digestion such as enzyme release, digestion product removal and gastric emptying. Digesta was collected from the stomach cannula of pigs to establish system parameters and to document the ability of the model to simulate gastric digestion. The results showed that the average pH of gastric digesta increased significantly from 2.47 to 4.97 after feed consumption and then decreased 140 min postprandial. The model described the decrease in pH within the pigs' stomach as $pH_t=5.182e^{-0.0014t}$, where t represents the postprandial time in minutes. The cumulative distribution function of liquid digesta was $V_t=64.509e^{0.0109t}$. The average pepsin activity in the liquid digesta was 317Anson units/mL. There was significant gastric emptying 220 min after feed consumption. The cybernetic dynamic system of gastric digestion was set according to the above data in order to compare with in vivo changes. The time course of crude protein digestion predicted by the model was highly correlated with observed in vivo digestion (r = 0.97; p = 0.0001), Model prediction for protein digestion was higher than that observed for a traditional static in vitro method (r = 0.89; p = 0.0001).