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PubMed | Institute of Jinan Red Ginseng, Sogang University, Chonbuk National University and Korea University
Type: Journal Article | Journal: Pharmaceutical biology | Year: 2016

Red ginseng (heat-processed Panax ginseng) is a well-known alternative medicine with pharmacological antidiabetic activity. It exerts pharmacological effects through the transformation of saponin into metabolites by the intestinal microbiota. Given that intestinal conditions and intestinal microflora vary among individuals, the pharmacological effects of orally administered red ginseng likely may vary among individuals.To overcome this variation and produce homogeneously effective red ginseng, we evaluated the antidiabetic effects of probiotic-fermented red ginseng in a mouse model.The antidiabetic efficacy of orally administered probiotic-fermented red ginseng was assessed in ICR mice after induction of diabetes using streptozotocin (170mg/kg body weight). Samples were given orally for 8 weeks, and indicators involved in diabetic disorders such as body weight change, water intake, blood glucose, glucose tolerance and various biochemical parameters were determined.Oral administration of probiotic-fermented red ginseng significantly decreased the level of blood glucose of about 62.5% in the fasting state and induced a significant increase in glucose tolerance of about 10.2% compared to the control diabetic mice. Additionally, various indicators of diabetes and biochemical data (e.g., blood glycosylated haemoglobin level, serum concentrations of insulin, and -amylase activity) showed a significant improvement in the diabetic conditions of the mice treated with probiotic-fermented red ginseng in comparison with those of control diabetic mice.Our results demonstrate the antidiabetic effects of probiotic-fermented red ginseng in the streptozotocin-induced mouse diabetes model and suggest that probiotic-fermented red ginseng may be a uniformly effective red ginseng product.


PubMed | Institute of Jinan Red Ginseng, Chonbuk National University and Dongguk University
Type: | Journal: International immunopharmacology | Year: 2016

Studies have been focused on natural products with antibacterial and anti-inflammatory activities, such as fucoidan. Many in vivo studies have evaluated the effect of fucoidan on tumor growth, diabetes, obesity, ischemia reperfusion, and oxidative stress. However, the effects of fucoidan on bacteria-induced gingival inflammation and periodontitis have not been reported. We previously characterized the anti-inflammatory effect of fucoidan in vitro. Here, we confirmed the anti-inflammatory activity of fucoidan in a macrophage cell line in terms of its inhibition of the expression of inflammatory mediators and pro-inflammatory cytokines. Additionally, we confirmed the ability of fucoidan to inhibit gingival inflammation, expression of pro-inflammatory cytokines, and neutrophil recruitment in the gingival tissue of mice injected with LPS prepared from P. gingivalis. Interestingly, however, fucoidan did not inhibit the expression of pro-inflammatory cytokines in a P. gingivalis-infected mouse model of periodontitis. Additionally, fucoidan treatment did not lead to clearance of P. gingivalis or improvement of P. gingivalis infection-mediated bone loss in the periodontitis model. We conclude that fucoidan exerts anti-inflammatory effects in vitro and in vivo, together with a limited antibacterial effect in vivo.


Park Y.M.,Sungkyunkwan University | Hwang S.J.,Sungkyunkwan University | Masuda K.,U.S. National Institutes of Health | Choi K.-M.,Institute of Jinan Red Ginseng | And 5 more authors.
Molecular and Cellular Biology | Year: 2012

MicroRNAs (miRNAs) have been implicated in the pathogenesis and progression of brain tumors. miR-21 is one of the most highly overexpressed miRNAs in glioblastoma multiforme (GBM), and its level of expression correlates with the tumor grade. Programmed cell death 4 (PDCD4) is a well-known miR-21 target and is frequently downregulated in glioblastomas in accordance with increased miR-21 expression. Downregulation of miR-21 or overexpression of PDCD4 can inhibit metastasis. Here, we investigate the role of heterogeneous nuclear ribonucleoprotein C1/C2 (hnRNPC) in the metastatic potential of the glioblastoma cell line T98G. hnRNPC bound directly to primary miR-21 (pri-miR-21) and promoted miR-21 expression in T98G cells. Silencing of hnRNPC lowered miR-21 levels, in turn increasing the expression of PDCD4, suppressing Akt and p70S6K activation, and inhibiting migratory and invasive activities. Silencing of hnRNPC reduced cell proliferation and enhanced etoposideinduced apoptosis. In support of a role for hnRNPC in the invasiveness of GBM, highly aggressive U87MG cells showed higher hnRNPC expression levels and hnRNPC abundance in tissue arrays and also showed elevated levels as a function of brain tumor grade. Taken together, our data indicate that hnRNPC controls the aggressiveness of GBM cells through the regulation of PDCD4, underscoring the potential usefulness of hnRNPC as a prognostic and therapeutic marker of GBM. © 2012, American Society for Microbiology.


Kim C.-D.,Sychar Maxface Center for Maxillofacial Surgery | Cha J.-D.,Institute of Jinan Red Ginseng | Li S.,Yanbian University | Cha I.-H.,Yonsei University
Archives of Oral Biology | Year: 2015

Background Acacetin (5,7-dihydroxy-40-methoxyflavone), present in safflower seeds, plants, flowers, Cirisium rhinoceros Nakai, has been reported to be able to exert anti-peroxidative, anti-inflammatory, anti-plasmodial, and anti-proliferative activities by inducing apoptosis and blocking the progression of cell cycles. Objective and design The objective of this study is to investigate the mechanism of acacetin-induced apoptosis of oral squamous cell carcinoma cell line (HSC-3). Results Acacetin caused 50% growth inhibition (IC50) of HSC-3 cells at 25 μg/mL over 24 h in the MTT assay. Apoptosis was characterized by DNA fragmentation and increase of sub-G1 cells and involved activation of caspase-3 and PARP (poly-ADP-ribose polymerase). Maximum caspase-3 activity was observed with 100 μg/mL of acacetin for 24 h. Caspase-8 and -9 activation cascades mediated the activation of caspase-3. Acacetin caused reduction of Bcl-2 expression leading to an increase of the Bax:Bcl-2 ratio. It also caused a loss of mitochondrial membrane potential that induced release of cytochrome c into the cytoplasm. Pretreatment with casapse-3 (Z-DEVD-FMK), -8 (Z-IETD-FMK), and 9 inhibitor (z-LEHD-fmk) inhibited the acacetin-induced loss of mitochondrial membrane potential and release of cytochrome c. The mitogen-activated protein kinases (MAPKs) were activated by acacetin. Moreover, pretreating the cells with each of the caspase inhibitor or MAPKs specific inhibitors apparently inhibited acacetin-induced cytotoxicity of HSC-3 cells. Conclusion In conclusion, acacetin induce the apoptosis of oral squamous cell carcinoma cell line, which is closely related to its ability to activate the MAPK-mediated signaling pathways with the subsequent induction of a mitochondria- and caspase-dependent mechanism. These results strongly suggest that acacetin might have cancer inhibition and therapeutic potential. © 2015 Elsevier Ltd Elsevier Ltd. All rights reserved.


Cha J.-D.,Institute of Jinan Red Ginseng | Lee J.-H.,Chonbuk National University | Choi K.M.,Institute of Jinan Red Ginseng | Choi S.-M.,Daegu Health College | Park J.H.,Dong - Eui University
Evidence-based Complementary and Alternative Medicine | Year: 2014

Cryptotanshinone (CT), a major tanshinone of medicinal plant Salvia miltiorrhiza Bunge, demonstrated strong antibacterial activity against clinic isolated methicillin and vancomycin-resistant Staphylococcus aureus (MRSA and VRSA) in this experiment. The CT was determined against clinic isolated MRSA 1-16 with MIC and MBC values ranging from 4 to 32 and 8 to 128 g/mL; for MSSA 1-2 from 16 to 32 g/mL and 64 to 128 g/mL; for VRSA 1-2 from 2 to 4 g/mL and 4 to 16 g/mL, respectively. The range of MICand MICof CT was 0.5-8 g/mL and 4-64 g/mL, respectively. The combination effects of CT with antibiotics were synergistic (FIC index < 0.5) against most of tested clinic isolated MRSA, MSSA, and VRSA except additive, MRSA 4 and 16 in oxacillin, MRSA 6, 12, and 15 in ampicillin, and MRSA 6, 11, and 15 in vancomycin (FIC index < 0.75-1.0). Furthermore, a time-kill study showed that the growth of the tested bacteria was completely attenuated after 2-6 h of treatment with the 1/2 MIC of CT, regardless of whether it was administered alone or with ampicillin, oxacillin, or vancomycin. The results suggest that CT could be employed as a natural antibacterial agent against multidrug-resistant pathogens infection. © 2014 Jeong-Dan Cha et al.


Lee K.-Y.,Chonbuk National University | Jeong M.-R.,Institute of Jinan Red Ginseng | Choi S.-M.,Daegu Health College | Na S.-S.,Chonbuk National University | Cha J.-D.,Institute of Jinan Red Ginseng
Archives of Oral Biology | Year: 2013

Background: Fucoidan is a sulphated polysaccharide that is primarily extracted from brown seaweeds; it has been broadly studied in recent years due to its numerous biological properties, including anticoagulant, antithrombotic, antitumour and antiviral activities. Objective and design: In this study, fucoidan was evaluated against oral bacteria, either alone or with antibiotics, via the broth dilution method and chequerboard and time-kill assay. Results: Minimum inhibitory concentration/minimum bactericidal concentration (MIC/MBC) values for the fucoidan against all the tested bacteria ranged between 0.125 and 0.50/0.25 and 1.00 mg ml-1, for ampicillin 0.125 and 64/0.5 and 64 μg ml-1 and for gentamicin 2 and 256/4 and 512 μg ml -1, respectively. Furthermore, the MIC and MBC were reduced to one half-eighth as a result of the combination of the fucoidan with antibiotics. One to 3 h of treatment with MIC50 of fucoidan with MIC50 of antibiotics resulted from an increase of the rate of killing in colony forming units (CFUs) ml-1 to a greater degree than was observed with alone. Conclusion: These results suggest that fucoidan is important in the antibacterial actions of the agents. © 2012 Elsevier Ltd.


Kho M.C.,Wonkwang University | Lee Y.J.,Wonkwang University | Cha J.D.,Institute of Jinan Red Ginseng | Choi K.M.,Institute of Jinan Red Ginseng | And 2 more authors.
Evidence-based Complementary and Alternative Medicine | Year: 2014

Overconsumption of fructose results in dyslipidemia, hypertension, and impaired glucose tolerance, which have documented correlation with metabolic syndrome. Gastrodia elata, a widely used traditional herbal medicine, was reported with anti-inflammatory and antidiabetes activities. Thus, this study examined whether ethanol extract of Gastrodia elata Blume (EGB) attenuate lipid metabolism and endothelial dysfunction in a high-fructose (HF) diet animal model. Rats were fed the 65% HF diet with/without EGB 100 mg/kg/day for 8 weeks. Treatment with EGB significantly suppressed the increments of epididymal fat weight, blood pressure, plasma triglyceride, total cholesterol levels, and oral glucose tolerance, respectively. In addition, EGB markedly prevented increase of adipocyte size and hepatic accumulation of triglycerides. EGB ameliorated endothelial dysfunction by downregulation of endothelin-1 (ET-1) and adhesion molecules in the aorta. Moreover, EGB significantly recovered the impairment of vasorelaxation to acetylcholine and levels of endothelial nitric oxide synthase (eNOS) expression and induced markedly upregulation of phosphorylation AMP-activated protein kinase (AMPK) in the liver, muscle, and fat. These results indicate that EGB ameliorates dyslipidemia, hypertension, and insulin resistance as well as impaired vascular endothelial function in HF diet rats. Taken together, EGB may be a beneficial therapeutic approach for metabolic syndrome. © 2014 Min Chul Kho et al.


Sung Y.-Y.,Korea Institute of Oriental Medicine | Kim S.-H.,Daejeon University | Kim D.-S.,Korea Institute of Oriental Medicine | Park S.H.,Korea Institute of Oriental Medicine | And 2 more authors.
Journal of Functional Foods | Year: 2014

The nutritional composition and anti-obesity activities of cereal bars containing Allium fistulosum extract (AFB) in high-fat diet-induced obese mice was determined. AFB is rich in vitamins C, B2, and B3, and B9 with high protein. Oral treatment of AFB in obese mice reduced body weight, lipid accumulation in liver and adipose tissue as well as adipocyte size, compared to the high fat diet control mice. AFB also decreased serum triacylglycerol, glucose, and insulin concentrations, with increased HDL-cholesterol and adiponectin levels. Furthermore, 5% AFB markedly increased mRNA expression of peroxisome proliferators activated receptor-γ, uncoupling protein-2 as well as β3-adrenoreceptor in the visceral adipose tissue. These results demonstrate that the cereal bar with A. fistulosum extract may potentially serve as nutraceutical for improvement of obesity and metabolic disorders. © 2013 Elsevier Ltd.


PubMed | Institute of Jinan Red Ginseng, Wonkwang University and Chonbuk National University
Type: Journal Article | Journal: Nutrients | Year: 2016

Metabolic syndrome including obesity, dyslipidemia and hypertension is a cluster of risk factors of cardiovascular disease. Fermentation of medicinal herbs improves their pharmacological efficacy. Red ginseng (RG), a widely used traditional herbal medicine, was reported with anti-inflammatory and anti-oxidant activity. Aim in the present study was to investigate that the effects of fermented red ginseng (FRG) on a high-fructose (HF) diet induced metabolic disorders, and those effects were compared to RG and losartan. Animals were divided into four groups: a control group fed a regular diet and tap water, and fructose groups that were fed a 60% high-fructose (HF) diet with/without RG 250 mg/kg/day or FRG 250 mg/kg/day for eight weeks, respectively. Treatment with FRG significantly suppressed the increments of body weight, liver weight, epididymal fat weight and adipocyte size. Moreover, FRG significantly prevented the development of metabolic disturbances such as hyperlipidemia and hypertension. Staining with Oil-red-o demonstrated a marked increase of hepatic accumulation of triglycerides, and this increase was prevented by FRG. FRG ameliorated endothelial dysfunction by downregulation of endothelin-1 (ET-1) and adhesion molecules in the aorta. In addition, FRG induced markedly upregulation of Insulin receptor substrate 1 (IRS-1) and glucose transporter type 4 (Glut4) in the muscle. These results indicate that FRG ameliorates obesity, dyslipidemia, hypertension and fatty liver in HF diet rats. More favorable pharmacological effects on HF diet induced metabolic disorders were observed with FRG, compared to an equal dose of RG. These results showed that the pharmacological activity of RG was enhanced by fermentation. Taken together, fermentated red ginseng might be a beneficial therapeutic approach for metabolic syndrome.


PubMed | Institute of Jinan red ginseng, Daegu Health College, Chonbuk National University and Pohang College
Type: | Journal: Archives of oral biology | Year: 2016

Sophora flavescens AITON (Leguminosae) is a typical traditional Korean medical herb considered to exhibit antibacterial, anti-inflammatory, and antipyretic effects, and is also used for the treatment of skin and mucosal ulcers, sores, diarrhea, gastrointestinal hemorrhage, arrhythmia, and eczema.This study examined the inhibitory effects of sophoraflavanone G (SF) of S. flavescens on the bacterial fibrillar protein, Antigen I/II (AgI/II)-N recombinant protein isolated from Streptococcus mutans(rAg I/II)-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2). The investigation was focused on whether SF could inhibit the production of proinflammatory mediators such as nitric oxide (NO) and prostaglandin (PG) E2 as well as the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-a, interleukin (IL)-6, nuclear factor (NF)-B and mitogen-activated protein kinases (MAPKs) in rAgI/II-stimulated RAW 264.7 cells using Griess reagent, Enzyme linked immunosorbent assay (ELISA), and Western blotting analysis.SG significantly inhibited the production of NO and PGE2 and pro-inflammatory cytokines, such as interleukin (IL)-1, IL-6, and tumor necrosis factor in Ag I/II-N-stimulated RAW264.7 cells, which were mediated by the down-regulation of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. The SF inhibited the phosphorylation of IB-, nuclear translocation of p65, and subsequent activation of NF- B in the rAgI/II-stimulated cells. In addition, the SF suppressed the rAgI/II-stimulated activation of ERK MAPK as well as the MAPK inhibitor significantly reduced the rAgI/II-induced production of NO and PGE2.Collectively, we suggest that the SF inhibits the expression and production of inflammatory mediators by blocking the ERK MAPK mediated pathway and inhibiting the activation of NF-B.

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