• Journal of Ginseng Research
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• v.35 no.1
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• pp.69-79
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• 2011

Hepatocellular carcinoma (HCC) is the fi fth most common malignancy in the world and complicates liver cirrhosis related to hepatitis C virus (HCV) in many cases. We evaluated the therapeutic effect of Korean red ginseng extract (KGE) in patients with chronic liver diseases. Thirty male and female patients with HCC and another thirty with liver cirrhosis were included. Each category was divided into two groups; the first was used as control group, and received medical therapy only and the second group received the medical therapy supplemented with KGE capsules. The treated group with HCC received three KGE capsules/day (900 mg) while the treated group with HCV received two KGE capsules/day (600 mg) for 11 weeks along with their medical therapy. All patients were subjected to clinical examination and laboratory investigations, including liver function tests (at baseline, after 6 weeks of treatment and at the end of the study) and abdominal ultrasonography. Patients showing focal hepatic lesions were subjected to triphasic spiral abdominal computerized tomography and alpha-fetoprotein (AFP). HCV RNA was determined quantitatively by Roche for patients in the HCV group. Results showed that the medical therapy alone failed to normalize the liver enzymes or decrease the virus concentration. KGE administration induced a significant improvement in liver function tests, decreased the tumor marker (AFP) levels, and decreased the viral titers in HCV patients. Thus, KGE demonstrated powerful therapeutic effects against HCV and liver cancer.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.04a
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• pp.74-74
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• 2018

Abeliophyllum distichum is Korea Endemic Plants and its genetic resources found from Korea only. Bioactivities of A. distichum such as antioxidant, anti-cancer, and anti-inflammatory studies have been proved through many researches. Whereas, there are no studies on the biological activity of its callus extracts. In this study, we investigated the antioxidant activities of callus extracts derived from A. distichum and its inhibitory effect on oxidative DNA damage. The antioxidant activities were assessed using radical scavenging assays with DPPH, ABTS, and reducing power assay and the inhibitory effects on oxidative DNA damage were measured using ${\varphi}-174$ RF I plasmid DNA cleavage assay. In addition, callus extracts derived from A. distichum showed high antioxidant acitivties and no cytotoxicity in NIH/3T3. Also, it has significantly suppressed expression of ${\gamma}$-H2AX and p53 protein and mRNA levels in NIH/3T3 cells exposed to oxidative stress. Therefore, the callus extracts derived from A. distichum has potential antioxidant activity that can provide protective effects against the oxidative DNA damage caused by free radicals. This study suggest that it is valuable as cosmetics and medicine for antioxidant and cancer preventive materials.

• Archives of Pharmacal Research
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• v.29 no.10
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• pp.890-897
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• 2006

In inflammatory responses, induction of cytokines and other immune regulator genes in macrophages by pathogen-associated signal such as lipopolysaccharide (LPS) plays a crucial role. In this study, the gene expression profile changes by LPS treatment in the macrophage/monocyte lineage cell line RAW264.7 was investigated. A 60-mer oligonucleotide microarray of which probes target 32381 mouse genes was used. A reverse transcription-in vitro translation labeling protocol and a chemileuminescence detection system were employed. The mRNA expression levels in RAW264.7 cells treated for 6 h with LPS and the control vehicle were compared. 747 genes were up-regulated and 523 genes were down-regulated by more than 2 folds. 320 genes showing more than 4-fold change by LPS treatment were further classified for the biological process, molecular function, and signaling pathway. The biological process categories that showed high number of increased genes include the immunity and defense, the nucleic acid metabolism, the protein metabolism and modification, and the signal transduction process. The chemokine-cytokine signaling, interleukin signaling, Toll receptor signaling, and apoptosis signaling pathways involved high number of genes differentially expressed in response to LPS. These expression profile data provide more comprehensive information on LPS-target genes in RAW264.7 cells, which will be useful in comparing gene expression changes induced by extracts and compounds from anti-inflammatory medicinal herbs.

• IMMUNE NETWORK
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• v.2 no.1
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• pp.25-34
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• 2002

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial hyperplasia and joint destruction. The synovial fibroblasts express cell adhesion molecules and have a role in adhesive interation with inflammatory cells in synovial tissue. It has been suggested that hypoxic conditioins are thought to exist in arthritic joints, and several studies indicate that reactive oxygen species (ROS) produced in hypoxic condition can initiate events that lead to pro-adhesive changes via increased expression of adhesion molecules. So, this study wsa designed to examine whether antioxidant can inhibit hypoxia-induced expression of ICAM-1 in cultured human synovial fibroblasts. Methods: Synovial fibroblasts were isolated from synovial tissue in patients with RA and cultured at hypoxic condition. Antioxidant, PDTC (pyrrolidine dithiocarbamate) were pre-treated for an hour before the hypoxic culture and synovial fibroblasts were harvested at 0, 6, 12, 24, 48 hours time points. Cell surface ICAM-1 expression in synovial fibroblasts was examined by the flow cytometric analysis. To analyse the expression of ICAM-1 mRNA, reverse-transcriptase polymerase chain reaction (RT-PCR) was performed. The levels of cytokines in culture supernatants were measured by ELISA, and activation of NF-${\kappa}B$ was analysed by electrophoretic mobility shift assay. The adhesive reaction between synovial fibroblasts and lymphocytes was assayed by measurement of fluorescent intensity of BCECF-AM in lymphocytes. Results: Hypoxic stimuli up-regulated the ICAM-1 expression as well as the adhesive interaction of human synvial fibroblasts to lymphocytes in a time-dependent manner, and PDTC inhibited hpyoxia-induced ICAM-1 expression and cell-cell interaction. PDTC also inhibited the hypoxia-induced activation of intracellular transcription factor, NF-${\kappa}B$. PDTC decreased the amount of hypoxia-induced production of IL-$1{\beta}$ and TNF-${\alpha}$. Conclusion: These studies demonstrate that PDTC inhibit the hypoxia-induced expression of the adhesion molecule, ICAM-1 and activation of NF-${\kappa}B$ in cultured human synovial fibroblasts.

• The Korea Journal of Herbology
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• v.35 no.5
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• pp.33-39
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• 2020

Objectives : Increasing evidence supports the biological and pharmacological activities of essential oils on the central nervous system such as pain, anxiety, attention, arousal, relaxation, sedation and learning and memory. The purpose of present work is to investigate the protective effect and molecular mechanism of cypress essential oil (CEO) against scopolamine (SCO)-induced cognitive impairments in C57BL/6 mice. Methods : A series of behavior tests such as Morris water maze, passive avoidance, and fear conditioning tests were conducted to monitor learning and memory functions. Immunoblotting and RT-PCR were also performed in the hippocampal tissue to determine the underlying mechanism of CEO. Results : SCO induced cognitive impairments as assessed by decreased step-through latency in passive avoidance test, relatively low freezing time in fear conditioning test, and increased time spent to find the hidden platform in Morris water maze test. Conversely, CEO inhalation significantly reversed the SCO-induced cognitive impairments in C57BL/6 mice comparable to control levels. To elucidate the molecular mechanisms of memory enhancing effect of CEO we have examined the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. CEO effectively elevated the protein as well as mRNA expression of BDNF via activation of cAMP response element binding protein (CREB). Conclusions : Our findings suggest that CEO inhalation effectively restored the SCO-impaired cognitive functions in C56BL/6 mice. This learning and memory enhancing effect of CEO was partly mediated by up-regulation of BDNF via activation of CREB.

• Journal of Korean Medicine Rehabilitation
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• v.18 no.3
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• pp.41-49
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• 2008

Objectives : The aim of this study is to investigate Daesiho-tang(Dachaihu-tang) water extracts (DSTE) have potent anti-obesity activities in a high-fat diet-induced obesity mouse model. Methods : In this study, we designed three groups (normal diet group, high-fat diet group, high-fat diet plus DSTE group for 7-weeks oral administration). Results : Increases in body weight were inhibited by 7-weeks oral administration of DSTE at a 500 mg/kg concentration in this animal model. Results from blood lipid analysis showed that the levels of triglyceride, total cholesterol and LDL-cholesterol were significantly lowered by DSTE administration, also HDL-cholesterol was increased more than high-fat diet-induced obese mouse. To understand the underlying mechanism at the molecular level, the effects of DSTE were examined on the expression of the genes involved in lipogenesis by real-time PCR. In epididymal fat and liver of DSTE-treated mice, the mRNA level of lipogenic genes such as sterol regulatory element binding protein 1 and fatty acid synthase were decreased, which was well correlated with the reduction of the tissues weight. Conclusions : These results suggest that DSTE may have great potential as a novel anti-obesity agent.

• Journal of Ginseng Research
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• v.39 no.4
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• pp.406-413
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• 2015

Background: Pathogenesis-related 10 (PR-10) proteins are small, cytosolic proteins with a similar three-dimensional structure. Crystal structures for several PR-10 homologs have similar overall folding patterns, with an unusually large internal cavity that is a binding site for biologically important molecules. Although structural information on PR-10 proteins is substantial, understanding of their biological function remains limited. Here, we showed that one of the PgPR-10 homologs, PgPR-10.3, shares binding properties with flavonoids, kinetin, emodin, deoxycholic acid, and ginsenoside Re (1 of the steroid glycosides). Methods: Gene expression patterns of PgPR-10.3 were analyzed by quantitative real-time PCR. The three-dimensional structure of PgPR-10 proteins was visualized by homology modeling, and docking to retrieve biologically active molecules was performed using AutoDock4 program. Results: Transcript levels of PgPR-10.3 expressed in leaves, stems, and roots of 3-wk-old ginseng plantlets were on average 86-fold lower than those of PgPR-10.2. In mature 2-yr-old ginseng plants, the mRNA of PgPR-10.3 is restricted to leaves. Ginsenoside Re production is especially prominent in leaves of Panax ginseng Meyer, and the binding property of PgPR-10.3 with ginsenoside Re suggests that this protein has an important role in the control of secondary metabolism. Conclusion: Although ginseng PR-10.3 gene is expressed in all organs of 3-wk-old plantlets, its expression is restricted to leaves in mature 2-yr-old ginseng plants. The putative binding property of PgPR-10.3 with Re is intriguing. Further verification of binding affinity with other biologically important molecules in the large hydrophobic cavity of PgPR-10.3 may provide an insight into the biological features of PR-10 proteins.

• Animal cells and systems
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• v.14 no.4
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• pp.283-289
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• 2010

Ssanghwa-tang (SHT) is a traditional Korean herbal medicine widely prescribed to decrease fatigue following an illness. The purpose of this study was to investigate the effects of SHT on osteoclast differentiation in vitro, and on bone loss in ovariectomized (OVX) rats in vivo. SHT significantly reduced the receptor activator for the nuclear factor ${\kappa}B$ (NF-${\kappa}B$) ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP) activity, and multinucleated osteoclast formation in RAW264.7 cells without affecting cell viability. In addition, SHT significantly attenuated RANKL-induced mRNA expression levels of c-Src and cathepsin K. To examine the in vivo effect of SHT on OVX-induced bone loss in OVX rats, we administered SHT (0.6 g/kg BID) orally to OVX rats for 12 weeks. SHT administration significantly blocked OVX-induced decrease of femoral bone mineral density (BMD) and femoral trabeculae in OVX rats. In conclusion, these results suggest that SHT treatment effectively prevents OVX-induced bone loss, and this effect may result from its inhibitory effect on osteoclast differentiation.

• Tuberculosis and Respiratory Diseases
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• v.42 no.4
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• pp.447-454
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• 1995

Cytokine release from alveolar macrophages and subsequent interaction of these cytokines with the bronchial epithelium can induce epithelial cells to release inflammatory mediators. Nitric oxide(NO), a highly reactive gas formed from arginine by nitric oxide synthase(NOS), is known to be involved in inflammation and edema formation, and the inducible form of NOS(iNOS) can be increased by cytokines. In this context, we hypothesized that lung epithelial cells could be stimulated by cytokines released by alveolar macrophages to express iNOS. To test this hypothesis, the murine lung epithelial cell line, LA-4, or the human lung epithelial cell line, A549, were stimulated with culture supernatant fluids from alveolar macrophages. NO production was assessed by evaluating the culture supernatant fluids for nitrite and nitrate, the stable end products of NO. Both murine and human cell culture supernatant fluids demonstrated an increase in nitrite and nitrate which were time- and dose-dependent and attenuated by $TNF{\alpha}$ and IL-$1{\beta}$ antibodies(p<0.05, all comparisons). Consistent with these observations, cytomix a combination of $TNF{\alpha}$, IL-$1{\beta}$, and $\gamma$-interferon, stimulated the lung epithelial cell lines as well as primary cultures of human bronchial epithelial cells to increase their NO production as evidenced by an increase in nitrite and nitrate in their culture supernatant fluids, an increase in the iNOS staining by immunocytochemistry, and an increase in iNOS mRNA by Northern blottin(p<0.05, all comparisons). The cytokine effects on iNOS were all attenuated by dexamethasone. To determine if these in vitro observations are reflected in vivo, exhaled NO was measured and found to be increased in asthmatics not receiving corticosteroids. These data demonstrate that alveolar macrophage derived cytokines increase iNOS expression in lung epithelial cells and that these in vitro observations are mirrored by increased exhaled NO levels in asthmatics. Increased NO in the lung may contribute to edema formation and airway narrowing.

• Journal of Ginseng Research
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• v.35 no.2
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• pp.200-208
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• 2011

Ginsenoside (G) $Rp_1$ is a ginseng saponin derivative with anti-cancer and anti-inflammatory activities. In this study, we examined the mechanism by which G-$Rp_1$ inhibits inflammatory responses of cells. We did this using a strategy in which DNA constructs containing cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) promoters were transfected into HEK293 cells. G-$Rp_1$ strongly inhibited the promoter activities of COX-2 and iNOS; it also inhibited lipopolysaccharide induced upregulation of COX-2 and iNOS mRNA levels in RAW264.7 cells. In HEK293 cells G-$Rp_1$ did not suppress TANK binding kinase 1-, Toll-interleukin-1 receptor-domain-containing adapter-inducing interferon-${\beta}$ (TRIF)-, TRIF-related adaptor molecule (TRAM)-, or activation of interferon regulatory factor (IRF)-3 and nuclear factor (NF)-${\kappa}$B by the myeloid differentiation primary response gene (MyD88)-induced. However, G-$Rp_1$ strongly suppressed NF-${\kappa}$B activation induced by I${\kappa}$B kinase (IKK)${\beta}$ in HEK293 cells. Consistent with these results, G-$Rp_1$ substantially inhibited IKK${\beta}$-induced phosphorylation of $I{\kappa}B{\alpha}$ and p65. These results suggest that G-$Rp_1$ is a novel anti-inflammatory ginsenoside analog that can be used to treat IKK${\beta}$/NF-${\kappa}$B-mediated inflammatory diseases.