• The Korea Journal of Herbology
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• v.36 no.6
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• pp.1-8
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• 2021

Objectives : Atractylodis rhizoma Alba has been traditionally used as a medicinal resource that is used for enhancing Qi (氣) in traditional medicine in Korea, China, and Japan. This study investigated the protective effects of Atractylodis rhizoma Alba extract (ARE) against trimethyltin (TMT), a neurotoxin that causes selective hippocampal injury, using both in vitro and in vivo models. Methods : We investigated the effects of ARE on TMT- (5mM) induced cytotoxicity in primary cultures of mouse hippocampal cells (7 days in vitro ) and on hippocampal injury in C57BL/6 mice injected with TMT (2.6 mg/kg). Results : We observed that ARE treatment (0 - 50 ㎍/mL) significantly reduced TMT-induced cytotoxicity in cultured hippocampal neurons in a dose-dependent manner, based on results of lactate dehydrogenase and 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assays. Additionally, this study showed that orally administered ARE (5 mg/kg; between -6 and 0 days before TMT injection) significantly attenuated seizures in adult mice. Furthermore, quantitative analysis of allograft inflammatory factor-1 (Iba-1)- and glial fibrillary acidic protein (GFAP)- positive cells showed significantly reduced levels of Iba-1- and GFAP-positive cell bodies in the dentate gyrus of mice treated with ARE prior to TMT injection. These findings indicate the significant protective effects of ARE against the TMT-induced massive activation of microglia and astrocytes in the hippocampus. Conclusions : We conclude that ARE minimizes the detrimental effects of TMT-induced hippocampal neurotoxicity, both in vitro and in vivo . Our findings may serve as useful guidelines to support ARE administration as a promising pharmacotherapeutic approach to hippocampal degeneration.

• Biomolecules & Therapeutics
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• v.30 no.6
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• pp.529-539
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• 2022

Rheumatoid arthritis (RA) is a multifactorial immune-mediated disease, the pathogenesis of which involves different cell types. T-cell activation plays an important role in RA. Therefore, inhibiting T-cell activation is one of the current therapeutic strategies. Cytotoxic T-lymphocyte antigen 4-immunoglobulin (CTLA4-Ig), also known as abatacept, reduces cytokine secretion by inhibiting T-cell activation. To achieve a homeostatic therapeutic effect, CTLA4-Ig has to be administered repeatedly over several weeks, which limits its applicability in RA treatment. To overcome this limitation, we increased the number of sialic acid-capped antennas by genetically engineering the CTLA4 region to increase the therapeutic effect of CTLA4-Ig. N-acetylglucosaminyltransferase (GnT) and α2,6-sialyltransferase (α2,6-ST) were co-overexpressed in Chinese hamster ovary (CHO) cells to generate a highly sialylated CTLA4-Ig fusion protein, named ST6. The therapeutic and immunogenic effects of ST6 and CTLA4-Ig were compared. ST6 dose-dependently decreased paw edema in a mouse model of collagen-induced arthritis and reduced cytokine levels in a co-culture cell assay in a similar manner to CTLA4-Ig. ST6- and CTLA4-Ig-induced T cell-derived cytokines were examined in CD4 T cells isolated from peripheral blood mononuclear cells after cell killing through irradiation followed by flow- and magnetic-bead-assisted separation. Interestingly, compared to CTLA4-Ig, ST6 was substantially less immunogenic and more stable and durable. Our data suggest that ST6 can serve as a novel, less immunogenic therapeutic strategy for patients with RA.

• The Korea Journal of Herbology
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• v.29 no.2
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• pp.23-31
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• 2014

Objectives : This study was undertaken to verify the effects of Massa Medicata Fermentata (MMF) on nonalcoholic fatty liver disease (NAFLD) using high fat diet-fed male mice. Methods : Fifty four male C57BL/6N mice (age matched) were used for all experiments. Nine standard chow diet-fed mice were used as normal group and forty five high fat diet-fed obese mice were randomly divided into 5 groups: control, atorvastatin-10mg/kg, MMF(1)-62.5mg/kg, MMF(2)-125mg/kg and MMF(3)-250mg/kg. After all groups were treated with several kinds of diets for 8 weeks, we measured body weight gain, adipose tissue weights, plasma lipid and glucose metabolism, visceral organ weights, histological analysis for liver on the mice. Results : MMF-treated mice had lower body weight gain compared with controls. Among MMF-treated mice, the effect was magnified in MMF(2). MMF(3)-treated mice had lower blood plasma total cholesterol (TC) and glucose level compared with controls. MMF decreased hepatic lipid accumulation, liver fibrosis and liver inflammation of mice compared with controls. The effects was maximized in MMF(2) and atorvastatin. Blood plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), ${\gamma}$-glutamyltransferase (${\gamma}$-GT) concentrations tends to be decreased by MMF compared with controls. Blood plasma AST, ALT, ${\gamma}$-GT concentrations and organ weights were not changed by MMF, indicating that all three kinds of MMF do not show any hepatotoxicity. Conclusions : These results suggest that MMF improves NAFLD by reducing body weight gain, hepatic lipid accumulation, liver fibrosis, liver inflammation.

• The Korea Journal of Herbology
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• v.28 no.4
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• pp.77-81
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• 2013

Objectives : Horse oil (HO) has been used long time as the folk medicine of many Asian countries such as Korea, Mongol, China, India and Japan. HO has been used for anti-bacterial, anti-inflammatory, and anti-pruritic purposes in skin. However, it is still largely unknown whether HO modulates the skin condition. In this study, we attempted to evaluate the anti-inflammatory effect of HO on the 1 % of 2, 4-dinitro-1-chlorobenzene (DNCB)-induced contact hypersensitivity in Balb/c mice. Methods : To find the anti-inflammatory effect of HO, contact hypersensitivity, a local inflammatory response of skin, was induced on the back of Balb/c mice by sensitization and repeated application by 1% DNCB and HO treated 2 weeks on the 1% of DNCB-treated Balb/c mice. Excised mice skins were stained with hematoxylin and eosin and serum IgE level was measured by mouse IgE ELISA kit. Results : In this study, we found that HO reduced erythema by 1% of DNCB treated Balb/c mice. Also, HO recovered histopathological features such as the thickening of epidermis, hyperkeratosis and the infiltration of inflammatory cells in 1% of DNCB treated Balb/c mice. In addition, HO reduced IgE level on the serum obtained from blood of 1% of DNCB-treated Balb/c mice. Conclusion : Taken together, these results showed that HO could be used as a pharmaceutical material with anti-inflammatory effects by reducing of erythema, IgE level and recovering of histopathological features skin on DNCB-induced contact hypersensitivity in Balb/c mice model.

• The Korea Journal of Herbology
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• v.32 no.5
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• pp.47-55
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• 2017

Objectives : Obesity is caused by the excess accumulation of fat in the body due to energy imbalance, and it causes various diseases. The aim of this study was to investigate an anti-obesity efficacy and an antioxidant activity of water from herbal mixture extract (SM17). Methods : The antioxidant activities were evaluated through radical scavenging assays using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radicals. To evaluated anti-obesity effect of SM17, we used a high fat diet fed mouse model. The SM17 (150 mg/kg body weight/day, p.o.) was treated every day for 6 weeks to C57BL/6 mice. Body weight and food intake were measured every day. The changes of reactive oxygen species (ROS), alanine aminotransferanse (ALT), aspartate aminotransferase (AST), triglycerids (TG) and total cholesterol (TC) in serum were analyzed after experiment. Also, expression of lipid metabolism related proteins were investigated by western blot analysis. Results : It was effective in antioxidant measurements, SM17 administration inhibited the biomarkers of lipid metaboism in serum and tissues. The administration of SM17 showed a significant reduction of body and tissue weight. Morever, it decreased ROS, ALT, AST, TG and TC in serum, compared with those of the obese mice. Adipogenesis-related protein expressions increased in obese mice compared to normal mice. However, SM17 group exhibited the down-expression of these proteins. Conclusion : A SM17 aqueous extract has a great effect on the stimulation (AMPK) activation, and may have a benefit to reduce a fatty acid metabolism through inhibition of lipid accumulation.

• The Korea Journal of Herbology
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• v.34 no.2
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• pp.41-47
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• 2019

Objectives : A traditional herbal prescription, Kyung-Ok-Ko (KOK), has long been used in oriental medicine as an invigorant for age-related diseases, such as amnesia and stroke. However, the beneficial value of KOK for immune responses is largely unknown. Based on the above mentioned effects of KOK, other previous reports, and its use in traditional medicine, we hypothesized that KOK displays beneficial effects against methotrexate (MTX)-induced immune suppression. Methods : We investigated the effects of KOK (0.6 g/kg/day, oral (p.o.)) on deteriorated immunity caused by MTX (2 mg/kg/day, p.o.) in an immune suppression mouse model. MTX was fed to mice once a day for 7 days. After the immune responses of the mice deteriorated by MTX treatment, KOK in water was fed to the mice once a day for 14 days. We then measured the expression levels of various cytokines, such as T helper cell (Th1, Th2) cytokines, and the number of immune cells, such as spleen T cells, B cells, and macrophages. Results : The data showed that MTX decreased Th1 profiles (interferon $(IFN)-{\gamma}$, interleukin (IL)-2, IL-12) and the number of immune cells, and increased Th2 profiles (IL-4, IL-5, IL-13), which were normalized significantly by post-administration of KOK. However, there was no significant difference in body-weight gain between MTX- and KOK-treated mice. Conclusion : These results indicate that KOK has immune-enhancing functions and reduces immunotoxicity of MTX, suggesting that supplementation with KOK will improve immune responses clinically and be useful for the prevention of immune-related diseases.

• Journal of the Korean Society of Radiology
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• v.16 no.2
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• pp.103-113
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• 2022

In this paper, a combined ¹⁸F-FDG(fluorodeoxyglucose) and MNP(magnetic nanoparticles) contrast agent was synthesized using N-(p-maleimidophenyl) isocyanate as the crosslinker for use in simultaneous PET-MRI scans. PET-MRI images were acquired and evaluated before and after injection of the combined contrast imaging agent (¹⁸F-FDG labeled MNP) from a glioma stem cell mouse model. After setting the region of interest (ROI) on each acquired image, the area of the lesion was calculated by segmentation. As a result, the PET image was larger than the MRI. In particular, the simultaneous PET-MRI images showed accurate lesions along with the surrounding soft tissue. The mean and standard deviation values were higher in the MRI images alone than in the PET images or the simultaneous PET-MRI images, regardless of whether the contrast agent was injected. In addition, the simultaneous PET-MRI image values were higher than for the PET images. For PSNR experiments, the original image was PET Image using 18F-FDG, MRI using MNPs, and MRI without contrast medium, and the target image was simultaneous PET-MRI image using 18F-FDG labeled MNPs contrast medium. As a result, all of them appeared significantly, suggesting that the 18F-FDG labeled MNPs contrast medium is useful. Future research is needed to develop an agent that can simultaneously diagnose and treat through SPECT-MRI imaging research that can use various nuclides.

• Journal of Physiology & Pathology in Korean Medicine
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• v.36 no.5
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• pp.181-186
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• 2022

Atractylodes macrocephala (AM) and Amomum villosum (AV) are the most common herbs in Korean Medicine to treat digestive diseases. In this study, we investigated the cholesterol lowering effects of mixtures of AM and AV extracts on high cholesterol diet (HCD) induced dyslipidemia mouse model. We classified animals into six different groups; Group 1: Normal diet, Group 2: HCD, Group 3: AV extracts : AM extracts (1:1) (200 mg/kg) + HCD, Group 4: AV extracts : AM extracts (1:2) (200 mg/kg) + HCD, Group 5: AV extracts : AM extracts (1:3) (200 mg/kg) + HCD, Group 6: Simvastatin 40 mg/kg + HCD. After 4 weeks of oral administration of respective drugs, we checked body, liver and epididymal fatweights along with liver and serum triacylglyceride (TG) concentration, total and low density lipoprotein (LDL) cholesterol in serum. Moreover, 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase (HMGCR), LDL receptor (LDLR), and sterol regulatory element-binding protein 2 (SREBP2) were detected by RT PCR or western blot analysis. The overall results showed that mixtures of AM and AV extracts inhibited HCD-induced increases of total cholesterol and LDL cholesterol in serum. Those effects seem to be caused by AM and AV extracts through inhibition of HMGCR expression. And thus blood cholesterol is induced into the liver by increasing LDLR expression, which is regulated by SREBP2 transcrption factor. The cholesterol lowering effects and mechanism of mixtures of AM and AV extracts was similar to the statin. We have identified the potential mixtures of AM and AV extracts as a new treatment for dyslipidemia.

• The Korea Journal of Herbology
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• v.24 no.1
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• pp.99-110
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• 2009

Objectives : The current treatment regimens for patients with nephrotic syndrome due to membranous nephropathy(MN) are based on steroids or immunosuppressive therapy with the aim of reducing proteinuria and improving outcome. Although these treatments attenuate the deterioration of renal function in MN patients, it has been suggested that all are burdened by significant toxicity. Therefore, more specific and less toxic therapies are needed. This study was to evaluate the effects of Coptidis Rhizoma Extract(CRE) on the MN induced by cBSA in mice. Methods : Mice were divided into 4 groups. One group named for 'Normal' was injected with a saline solution not to be immunized. The rest groups were treated as follows; After mice were immunized with 0.2 mg of cBSA and Freund's complete adjuvant one time every two weeks for 6 weeks, they received intra-peritoneal injection of 10 mg/kg of cBSA daily for 4 weeks. Also, they were divided into 3 groups. The first named for 'Control' was not given CRE. The second for 'CRE-250' was given oral administration of 250 mg/kg of CRE daily for 4 weeks. The third for 'CRE-500' was given 500 mg/kg of CRE. All of mice were sacrificed 4 weeks after the first immunization. We measured a body weight and 24hrs proteinuria as well as serological analysis. The morphologic changes of renal glomeruli were also observed with a light microscope and an electron microscope. Results : The levels of 24 hrs proteinuria, triglyceride, IgG, IL-6 were significantly decreased in both CRE groups. And the level of IgM was significantly decreased in CRE-250 group. In histological findings of kidney tissue, thickening of GBM and deposition of electron-density were consideraly decreased in both CRE groups. Conclusions : The present study suggests that CRE is highly effective when treating mice with MN induced by cBSA. More clinical data and studies are to be done for efficient application.

• Nutrition Research and Practice
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• v.17 no.2
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• pp.371-385
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• 2023

BACKGROUND/OBJECTIVES: Soy isoflavone (SIF) and soy lecithin (SL) have beneficial effects on many chronic diseases, including neurodegenerative diseases. Regretfully, there is little evidence to show the combined effects of these soy extractives on the impairment of cognition and abnormal cerebral blood flow (CBF). This study examined the optimal combination dose of SIF + SL to provide evidence for improving CBF and protecting cerebrovascular endothelial cells. MATERIALS/METHODS: In vivo study, SIF50 + SL40, SIF50 + SL80 and SIF50 + SL160 groups were obtained. Morris water maze, laser speckle contrast imaging (LSCI), and hematoxylin-eosin staining were used to detect learning and memory impairment, CBF, and damage to the cerebrovascular tissue in rat. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the oxidized glutathione (GSSG) were detected. The anti-oxidative damage index of superoxide dismutase (SOD) and glutathione (GSH) in the serum of an animal model was also tested. In vitro study, an immortalized mouse brain endothelial cell line (bEND.3 cells) was used to confirm the cerebrovascular endothelial cell protection of SIF + SL. In this study, 50 µM of Gen were used, while the 25, 50, or 100 µM of SL for different incubation times were selected first. The intracellular levels of 8-OHdG, SOD, GSH, and GSSG were also detected in the cells. RESULTS: In vivo study, SIF + SL could increase the target crossing times significantly and shorten the total swimming distance of rats. The CBF in the rats of the SIF50 + SL40 group and SIF50 + SL160 group was enhanced. Pathological changes, such as attenuation of the endothelium in cerebral vessels were much less in the SIF50 + SL40 group and SIF50 + SL160 group. The 8-OHdG was reduced in the SIF50 + SL40 group. The GSSG showed a significant decrease in all SIF + SL pretreatment groups, but the GSH showed an opposite result. SOD was upregulated by SIF + SL pretreatment. Different combinations of Genistein (Gen)+SL, the secondary proof of health benefits found in vivo study, showed they have effective anti-oxidation and less side reaction on protecting cerebrovascular endothelial cell. SIF50 + SL40 in rats experiment and Gen50 + SL25 in cell test were the optimum joint doses on alleviating cognitive impairment and regulating CBF through protecting cerebrovascular tissue by its antioxidant activity. CONCLUSIONS: SIF+SL could significantly prevent cognitive defect induced by β-Amyloid through regulating CBF. This kind of effect might be attributed to its antioxidant activity on protecting cerebral vessels.