• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.2
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• pp.290-294
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• 2002

The aim of this study was to investigate in an in vivo model the effects of ethanol extract and ethyl ether and ethyl acetate fractions of Sedum sarmentosum Bunge (SS). To investigate the effects of ethanol extract and ethyl ether and ethyl acetate fractions, Sprage-Dawley female rats were randomly assigned to groups as follows : Sham, OVX-control and ovariectomized rats supplemented with SS at 50 mg/kg bw/day, with SS at 100 mg/kg bw/day, with SS at 200 mg/kg bw/day, with ethyl ether fraction of SS at 10 mg/ka bw/day and with ethyl acetate fraction of SS at 10 mg/kg bw/day. Food intake and food efficiency ratio were not significantly different in groups. But body weight gain was decreased by supplementation of ethyl acetate fraction of SS compared to OVX-control. The levels of total cholesterol and triglyceride in serum were higher in ovariectomized control rats than Sham-operated rats, but supplementation of SS ethanol extracts at 200 mg/kg bw/day decreased the level of the lipid in serum. The level of HDL-cholesterol in serum increased by supplementation of SS ethanol extracts at 200 mg/kg bw/day (p<0.01). The levels of total cholesterol and triglyceride in serum were decreased by supplementation of ethyl acetate fraction of SS (p<0.01). On the other hand, the level of HDL-cholesterol in serum was increased by supplementation of ethyl acetate fraction of SS (p<0.05). On conclusion, it might be expected that ethanol extract and ethyl acetate fraction of SS is believed to be a possible protective effects for the fatty serum increasing serum lipid.

• KSBB Journal
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• v.19 no.2
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• pp.138-142
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• 2004

Cigarette smoke causes atypical structure of pulmonary (cell structural) and oxidative damage. Therefore, we carried out to determine if exposure to cigarette smoke alters pulmonary structure and anti-oxidant related enzyme in a ICR mice model, when natural product extracts using by manual sprayer. The mice were divided into five groups, control group, sham-treated group (Sham), natural product extracts-treated group (NPE), natural product extracts-treated with smoke-exposed group (NPE-SM) and smoke-exposed (SM) group. All groups are similar to control group in weight, but SM group is lower than the other groups. Microscopic image of the pulmonary structure in SM group showed deleterious alterations in the morphology, but the other groups are maintained in original structure. In anti-oxidant related enzyme, SOD (superoxide dismutase) and catalase, SM group represents the lowest enzyme activity among all groups. These results indicate that the natural product extracts is an efficient tissue protective agent against smoke-induced lung injury.

• Food Science and Biotechnology
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• v.15 no.3
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• pp.413-417
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• 2006

The purpose of this study was to investigate the hypoglycemic effect of Saururus chinensis Baill in vitro and in vivo. Methanol extract of S. chinensis Baill inhibited yeast ${\alpha}$-glucosidase activity by 49.8%, which was twice as strong as that of acarbose at a concentration of 0.5 mg/mL in vitro. The effect of S. chinensis Baill methanol extract on the postprandial increase in blood glucose levels was studied in streptozotocin-induced diabetic rats using a carbohydrate load test. Oral administration of S. chinensis Baill extract (500 mg/kg) significantly decreased incremental blood glucose levels at 60 and 90 min (p<0.05) after oral ingestion of starch (1 g/kg). The area under the glucose response curve of the S. chinensis Baill group was significantly decreased compared to that of the control group (p<0.05). The effect of prolonged feeding of S. chinensis Baill was studied in an animal model of type 2 diabetes. Three-week-old db/db mice were fed an AIN-93G diet or a diet containing 0.5% S. chinensis Baill extract for 7 weeks after 1 week of adaptation. Plasma glucose, insulin, and blood glycated hemoglobin levels of the mice fed S. chinensis Baill extract were significantly lower than those of the control group (p<0.05). Therefore, we conclude that S. chinensis Baill is effective in controlling hyperglycemia in animal models of diabetes mellitus.

• Laboraroty Animal Research
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• v.34 no.4
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• pp.302-310
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• 2018

CD47 (integrin-associated protein), a multi-spanning transmembrane protein expressed in all cells including red blood cells (RBCs) and leukocytes, interacts with signal regulatory protein ${\alpha}$ ($SIRP{\alpha}$) on macrophages and thereby inhibits phagocytosis of RBCs. Recently, we generated a novel C57BL/6J CD47 knockout ($CD47^{-/-}$ hereafter) mouse line by employing a CRISPR/Cas9 system at Center for Mouse Models of Human Disease, and here report their hematological phenotypes. On monitoring their birth and development, $CD47^{-/-}$ mice were born viable with a natural male-to-female sex ratio and normally developed from birth through puberty to adulthood without noticeable changes in growth, food/water intake compared to their age and sex-matched wild-type littermates up to 26 weeks. Hematological analysis revealed a mild but significant reduction of RBC counts and hemoglobin in 16 week-old male $CD47^{-/-}$ mice which were aggravated at the age of 26 weeks with increased reticulocyte counts and mean corpuscular volume (MCV), suggesting hemolytic anemia. Interestingly, anemia in female $CD47^{-/-}$ mice became evident at 26 weeks, but splenomegaly was identified in both genders of $CD47^{-/-}$ mice from the age of 16 weeks, consistent with development of hemolytic anemia. Additionally, helper and cytotoxic T cell populations were considerably reduced in the spleen, but not in thymus, of $CD47^{-/-}$ mice, suggesting a crucial role of CD47 in proliferation of T cells. Collectively, these findings indicate that our $CD47^{-/-}$ mice have progressive hemolytic anemia and splenic depletion of mature T cell populations and therefore may be useful as an in vivo model to study the function of CD47.

• Translational and Clinical Pharmacology
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• v.26 no.4
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• pp.160-165
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• 2018

Indobufen ($Ibustrin^{(R)}$), a reversible inhibitor of platelet aggregation, exists in two enantiomeric forms in 1:1 ratio. Here, we characterized the anti-platelet effect of S- and R-indobufen using response surface modeling using $NONMEM^{(R)}$ and predicted the therapeutic doses exerting the maximal efficacy of each enantioselective S- and R-indobufen formulation. S- and R-indobufen were added individually or together to 24 plasma samples from drug-naïve healthy subjects, generating 892 samples containing randomly selected concentrations of the drugs of 0-128 mg/L. Collagen-induced platelet aggregation in platelet-rich plasma was determined using a Chrono-log Lumi-Aggregometer. Inhibitory sigmoid $I_{max}$ model adequately described the anti-platelet effect. The S-form was more potent, whereas the R-form showed less inter-individual variation. No significant interaction was observed between the two enantiomers. The anti-platelet effect of multiple treatments with 200 mg indobufen twice daily doses was predicted in the simulation study, and the effect of S- or R-indobufen alone at various doses was predicted to define optimal dosing regimen for each enantiomer. Simulation study predicted that 200 mg twice daily administration of S-indobufen alone will produce more treatment effect than S-and R-mixture formulation. S-indobufen produced treatment effect at lower concentration than R-indobufen. However, inter-individual variation of the pharmacodynamic response was smaller in R-indobufen. The present study suggests the optimal doses of R-and S-enantioselective indobufen formulations in terms of treatment efficacy for patients with thromboembolic problems. The proposed methodology in this study can be applied to the develop novel enantio-selective drugs more efficiently.

• Journal of Ginseng Research
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• v.45 no.2
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• pp.325-333
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• 2021

Background: Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders. Enhancing hippocampal neurogenesis by promoting proliferation and differentiation of neural stem cells (NSCs) is a promising therapeutic strategy for AD. 20(S)-protopanaxadiol (PPD) and oleanolic acid (OA) are small, bioactive compounds found in ginseng that can promote NSC proliferation and neural differentiation in vitro. However, it is currently unknown whether PPD or OA can attenuate cognitive deficits by enhancing hippocampal neurogenesis in vivo in a transgenic APP/PS1 AD mouse model. Here, we administered PPD or OA to APP/PS1 mice and monitored the effects on cognition and hippocampal neurogenesis. Methods: We used the Morris water maze, Y maze, and open field tests to compare the cognitive capacities of treated and untreated APP/PS1 mice. We investigated hippocampal neurogenesis using Nissl staining and BrdU/NeuN double labeling. NSC proliferation was quantified by Sox2 labeling of the hippocampal dentate gyrus. We used western blotting to determine the effects of PPD and OA on Wnt/GSK3β/β-catenin pathway activation in the hippocampus. Results: Both PPD and OA significantly ameliorated the cognitive impairments observed in untreated APP/PS1 mice. Furthermore, PPD and OA significantly promoted hippocampal neurogenesis and NSC proliferation. At the mechanistic level, PPD and OA treatments resulted in Wnt/GSK-3β/β-catenin pathway activation in the hippocampus. Conclusion: PPD and OA ameliorate cognitive deficits in APP/PS1 mice by enhancing hippocampal neurogenesis, achieved by stimulating the Wnt/GSK-3β/β-catenin pathway. As such, PPD and OA are promising novel therapeutic agents for the treatment of AD and other neurodegenerative diseases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.36 no.6
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• pp.209-212
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• 2022

We recently reported that Gastrodia elata extracts (GEE) had an effects to protect against lipopolysaccharide-induced cognitive impairment in vivo model. In this study, we investigated the neuroprotective effects and the mechanism of action of GEE in hydrogen peroxide (H₂O₂)-induced cell death of SH-SY5Y human neuroblastoma cell. The SH-SY5Y cells were divided into five groups, including control(non-treated group), 100 μM H₂O₂, 100, 200, 500 ㎍/㎖ GEE+ 100 μM H₂O₂ groups. Pre- and co-treatment with GEE prevented cell death induced by 100 μM H₂O₂ for 24 h in SH-SY5Y cells. Our findings also showed that anti-oxidants enzymes (Cu/Zn superoxide dismutase, Mn superoxide dismutase, catalase) were up-regulated by 100 μM H₂O₂. But GEE suppressed H₂O₂-induced anti-oxidants enzymes decrease in a dose-dependent manner. Treatment with GEE also inhibited phosphorylation of eukaryotic initiation factor-2α (eIF-2α) and p38 by H₂O₂. Taken together, the neuroprotective effects of GEE in terms of recovery of antioxidant enzymes expression, down-regulation of eIF-2α and p38 phosphorylation, and inhibition of cell death are associated with reduced oxidative stress in SH-SY5Y cells.

• 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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.1
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• pp.24-29
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• 2014

The effects of Lycii fructus and Lycii folium on osteoporosis and serum cholesterol levels were tested in ovariectomized (OVX) rats. Twenty-four female Sprague-Dawley rats were divided into four groups: Sham group (sham-operated), Control group (OVX, ovariectomized model), LCF group (Ovx+Lycii fructus extract), and LCL group (OVX+Lycium folium extract). After 8 weeks, the OVX ($330{\pm}5.39$ g), LCF ($315{\pm}2.99$ g), and LCL ($318{\pm}2.06$ g) groups showed increased body weight compared with sham group ($281{\pm}1.71$ g). The levels of serum osteocalcin (OC) also increased in the LCF ($444.6{\pm}26.9$ ng/mL) and LCL ($407{\pm}18.9$ ng/mL) groups compared with the OVX group ($107{\pm}3.52$ ng/mL). The activities of serum alkaline phosphatase (ALP) increased in the LCF ($108{\pm}2.7$ U/L) and LCL ($407{\pm}18.9$ ng/mL) groups compared with the OVX group ($95{\pm}2.9$ U/L). Stereomicroscopy found that the low bone density that developed in the OVX group was significantly reversed in the LCF and LCL groups after 8 weeks. We also obtained molecular-based in vivo evidence that supports a mechanism of action involving novel estrogen receptor ($ER{\alpha}$) modulator in the uterus. We found that expression of ER${\alpha}$ mRNA in the OVX rat uterus was elevated by Lycium chinense. These results suggest that Lycii fructus and Lycii folium administered to rats during 8 weeks after oophorectomy may partially recover postmenopausal osteoporosis or delay the progression of osteoporotic changes.

• Journal of Applied Biological Chemistry
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• v.64 no.1
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• pp.89-96
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• 2021

The aim of this study is to examine the effect of Caulerpa okamurae ethanol extract (COE) on glucose metabolism and insulin sensitivity as one of the drug targets for treatment of type2 diabetes. COE significantly inhibited protein tyrosine phosphatase (PTP1B) and dipeptidyl peptidase-IV (DPP-IV) enzyme activities in vitro assay. Also, COE significantly enhanced the glucose uptake and the expression of insulin receptor substrate-1 (IRS-1) and glucose transporter4 (GLUT4) proteins in 3T3-L1 adipocytes or zebrafish larvae compared with control. In dexamethasone-induced resistance model of L6 myotubes, the protein expression of insulin signaling and glucose uptake was effectively increased by the treatment of COE. In contrast, the elevated phosphorylation of IRS-1 Ser307 was normally suppressed by treatment of COE. However, COE had no effect on insulin secretion in pancreatic beta cells. Thus, our results suggest that COE improves the glucose metabolism and insulin sensitivity through the regulation of insulin signaling and GLUT4 protein in insulin's target cells and zebrafish larvae.