• The Korean Journal of Physiology and Pharmacology
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• v.14 no.6
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• pp.391-397
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• 2010

E2F transcription factors and their target genes have been known to play an important role in cell growth control. We found that curcumin, a polyphenolic phytochemical isolated from the plant Curcuma longa, markedly suppressed E2F4 expression in HCT116 colon cancer cells. Hydrogen peroxide was also found to decrease E2F4 protein level, indicating the involvement of reactive oxygen species (ROS) in curucmin-induced downregulation of E2F4 expression. Involvement of ROS in E2F4 downregulation in response to curcumin was confirmed by the result that pretreatment of cells with N-acetylcystein (NAC) before exposure of curcumin almost completely blocked the reduction of E2F4 expression at the protein as well as mRNA level. Anti-proliferative effect of curcumin was also suppressed by NAC which is consistent to previous reports showing curcumin-superoxide production and induction of poly (ADP-ribose) polymerase (PARP) cleavage as well as apoptosis. Expression of several genes, cyclin A, p21, and p27, which has been shown to be regulated in E2F4-dependent manner and involved in the cell cycle progression was also affected by curcumin. Moreover, decreased (cyclin A) and increased (p21 and p27) expression of these E2F4 downstream genes by curcumin was restored by pretreatment of cells with NAC and E2F4 overexpression which is induced by doxycycline. In addition, E2F4 overexpression was observed to partially ameliorate curcumin-induced growth inhibition by cell viability assay. Taken together, we found curcumin-induced ROS down-regulation of E2F4 expression and modulation of E2F4 target genes which finally lead to the apoptotic cell death in HCT116 colon cancer cells, suggesting that E2F4 appears to be a novel determinant of curcumin-induced cytotoxicity.

• Journal of Nutrition and Health
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• v.39 no.8
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• pp.721-727
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• 2006

This study was conducted to investigate the effects of Aralia elata, Acanthopanacis cortex and Ulmus davidiana water extracts on blood hemoglobin, $HbA_{1c}$, levels and biomarkers in the streptozotocin (STZ)-induced diabetic rats. Male Wistar rats divided into normal and diabetic groups. The diabetic groups subdivided into the control group (DM) and Araliaceae water extracts supplemented groups: Aralia elata (AE), Acanthopanacis cortex (AC) and Ulmus davidiana (UD). The extracts were supplemented in diet base on 11.42 g of raw Araliaceae/kg diet for 7 weeks. The diabetes was induced by injecting 572 (55 mg/kg B.W., i.p.) once 2 weeks before sacrifying. Relative weights of liver were significantly lowered in the DM group compared to the normal group, whereas those of kidney and heart were significantly increased in the DM group. Supplementation of the Araliaceae water extracts improved reduced liver weights in STZ-induced diabetic rats. Blood glucose level was significantly higher in the DM group than in the normal group, whereas insulin contents were significantly lowered in the DM groups. However, these parameters were normalized in the An, AC and UD supplemented groups, respectively. Blood hemoglobin and $HbA_{1c}$ levels were significantly higher in the DM group than in the normal group. When all of Araliaceae water extracts were supplemented to the diabetic rats lowered hemoglobin and $HbA_{1c}$ levels. Red blood cell, white blood cell and Lymphocyte were significantly higher in the DM group than in the normal group. The supplementation of Araliaceae family water extracts significantly lowered these parameters compared to the DM group. MCV, MCH contents were declined in the DM group, while the supplementation of Aralia elata, Acanthopanacis cortex and Ulmus davidiana water extracts elevated of these contents in STZ-induced diabetic rats. Accordingly, these results indicate that Aralia elata, Aeanthopanacis corex and Ulmus davidiana water extracts would seem to improve the blood biomarkers in STZ-induced diabetic rats.

• Journal of Acupuncture Research
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• v.24 no.4
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• pp.81-97
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• 2007

Objective: The purpose of this study was to observe the effects of Cnidii Rhizoma herbal-acupuncture solution(CR-HAS) at Joksamni($ST_{36}$) on arthritis induced by Collagen II in mice. Methods : The author performed several experimental items. The severity of arthritis, changes of mouse weight, size of the spleen and the degree of stenosis, changes of cytokine level, IgG, IgM and anti-collagen II, changes of immunocyte count, histological changes of the CIA mouse joint were analyzed. Results: 1. In the CR-HA, the arthritis index, the incidence of arthritis, the degree of joint edema was significantly decreased. 2. In the CR-HA, weight, spleen size and stenosis rate was low and maintained as the normal group was. 3. In the CR-HA, cytokine level, IgG, IgM and anti-collagen II were significantly decreased. 4. In the CR-HA, on changes of immunocyte count were maintained to the levels of normal group. 5. In histological changes of the CIA mouse joint, the cartilage destruction and synovial cell proliferation were decreased. Conclusions : These results suggest that CR-HA at the $ST_{36}$ has an important role to control the immune reactions and suppress inflammatory response on the collagen induced rheumatoid arthritis. This study can be a significant supporting evidence that CR-HA will be chosen to be the principal therapy for clinical practice of the rheumatoid arthritis in the future.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.5
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• pp.1095-1105
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• 2009

This study was carried out to know the immunological effect of GDGT on CIA(collagen induced arthritis) mice, a model of rheumatoid arthritis. For this purpose, GDGT was orally administerd to mice with arthritis induced by collagen II and then value of cytotoxicity on hFLSs and liver, the arthritis index, immunocyte in paw joint and DNL, rheumatoid factor (IgG and IgM), collagen II specific antibody in the serum were measured. The cytotoxicity were not shown on hFLSs and liver. The arthritis index decreased significantly after 3 week. In total cell counts of DLN and paw joint, there was a significant increase in DLN and significant decrease in paw joint. In DNL, $CD19^+$, $CD3^+$, $CD4^+$, $CD3^+/CD69^+$, $CD8^+$, $CD4^+/CD25^+$, $ CD3^+/CD49b^+$ cells increased significantly. In Paw joints, $CD3^+$, $ CD4^+$, $CD4^+/CD25^+$ cells decreased significantly. The level of serum IgG and IgM decreased significantly. The level of collagen II in the serum was decreased significantly. Marginal erosion, necrotic chodrocytes, cartilage and bone degradation were improved in histological section of paw joints. The results present significant immunological effect of GDGT on rats with arthritis induced by collgen II. So we expect that GDGT should be used as a effective drugs for not only rheumatoid arthritis but also another auto-immune disease.

• The Journal of Korean Medicine
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• v.32 no.2
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• pp.63-78
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• 2011

Objective: This study aimed to evaluate the protective effects of Maekmundong-tang (MMDT) on an elastase-induced COPD model. Materials and Methods: The extract of MMDT was treated to A549 cells and elastase-induced COPD mice model. Then, various parameters such as cell-based cytoprotective activity and histopathological findings were analyzed. Results: MMDT showed a protective effect on elastase-induced cytotoxicity in A549 cells. This effect was correlated with analysis for caspase 3 levels, collagen and elastin contents, protein level of Cdk1, and gene expression of TNF-${\alpha}$ and IL-$1{\beta}$ in A549 cells. MMDT treatment also revealed a protective effect on the elastase-induced COPD mice model. This effect was evidenced via histopathological finding including immunofluorescence stains against elastin, collagen, and caspase 3, and protein level of Cdc2 in lung tissue. Conclusion: These data suggest that MMDT has pharmaceutical properties on COPD. This study can provide scientific evidence for the efficacy of MMDT for clinical application to patients with COPD.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.6
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• pp.479-486
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• 2000

The aim of this study was to clarify the mechanism of the inhibitory action of carbon monoxide (CO) on contraction, by measuring cytosolic $Ca^{2+}$ level $([Ca^{2+}]_i)$ and ionic currents in guinea-pig ileum. CO (10%) inhibited 40 mM KCl-induced contraction and this effect was blocked by ODQ $(1\;{\mu}M),$ a soluble guanylyl cyclase (sGC) inhibitor. CO inhibited the 40 mM KCl-induced contraction without changing $[Ca^{2+}]_i.$ Cumulative addition of KCl induced a graded increase in $[Ca^{2+}]_i$ and muscle tension. In the presence of CO, cumulative addition of KCl induced smaller contraction than in the absence of CO. On the other hand, the increase in $[Ca^{2+}]_i$ induced by cumulative addition of KCl was only slightly decreased in the presence of CO, and the $[Ca^{2+}]_i-tension$ relationship shifted downwards. Using the patch clamp technique with a holding potential of -60 mV, we found that CO had little effect on the peak Ba currents $(I_{Ba})$ when voltage was stepped from -60 mV to 0 mV. In addition, CO showed no effect on the depolarization-activated outward $K^+$ currents in the all potential ranges. We conclude that CO inhibits smooth muscle contraction mainly by decreasing the $Ca^{2+}$ sensitivity of contractile elements via a cGMP-dependent pathway, not by involving L-type $Ca^{2+}$ and outward-potassium currents in guinea-pig ileum.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.4
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• pp.641-649
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• 2011

This study was purposed to evaluate the effects of root of Liriope spicata (RLS) on LPS-induced COPD (chronic obstructive pulmonary disease) model. The extract of RLS was treated to A549 cells and LPS-induced COPD mice model. Then, various parameters such as cell-based cyto-protective activity and histopathological finding were analyzed. RLS showed a protective effect on LPS-induced cytotoxicity in A549 cells. This effect was correlated with analysis for caspase 3 levels, protein level of cyclin B1, Cdc2, and phospho-Erk1/2, and gene expression of TNF-${\alpha}$ and IL-$1{\beta}$ in A549 cells. RLS treatment also revealed the protective effect on LPS-induced lung injury in COPD mice model. This effect was evidenced via histopathological finding including immunofluence stains against caspase 3, and protein level of cyclin B1, Cdc2, and Erk1/2 in lung tissue. These data suggest that RLS has a pharmaceutical properties on lung injury. This study would provide an scientific evidence for the efficacy of RLS for clinical application to patients with COPD.

• Journal of Haehwa Medicine
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• v.16 no.2
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• pp.131-145
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• 2007

To evaluate the effects of GP on contact dermatitis, we examined the composition of immune cells from drain lymph node in DNCB-induced contact dermatitis murine model NC/Nga mice. And the amount of pathologic cytokines of spleen and antioxidant activity were investigated. The results were summarized as followers; 1. GP did not show cytotoxic effect on mLFC in vitro. 2. GP did not have hepatotoxicity in vivo in the level of ALT, AST. 3. GP decreased the production of DPPH and in a dose-dependent. 4. GP significantly decreased total cell number of DLN in DNCB-induced NC/Nga mice compared to the untreated control group. 5. GP significantly decreased the number of CD3+, CD19+, CD4+, CD8+, CD3+/CD69+ and CD4+/CD45+ in DLN of DNCB-induced NC/Nga mice compared to the untreated control group. 6. GP significantly reduced the level of IL-4 and IFN-$\gamma$ in splenocytes of DNCB-induced NC/Nga mice compared to the untreated control group. Taken together above results, GP have therapeutic effects on contact dermatitis by regulating T cell activation. This study warranted further investigations of molecular mechanisms of GP on contact dermatitis.

• Journal of Society of Preventive Korean Medicine
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• v.12 no.2
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• pp.51-59
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• 2008

Objectives : Buplueri Radix (BR), used medical plant in Korea traditional medicine, contains various compounds, including a series of triterpene saponins known as saikosaponins. We performed this study for the protective effect of BR against oxidative damage induced by 1,2,4-benzentriol(BT) in human lymphocytes. Methods : In order to investigate the protective effect of BR against carcinogens, genotoxicity induced by benzene metabolite, BT were performed using cytokinesis-block micronucleus(CBMN) assay and comet assay. Results : The frequency of micronucleus at 25, 50 and $100{\mu}M$ concentration of BT were $8{\pm}2.36$, $23{\pm}2.31$, $35{\pm}4.17$ respectively. In addition of BR with concentration of 25 and $50{\mu}g/mL$, MN frequencies were significantly decreased. According to comet assay, BT induced DNA damage in a dose-dependent manner at concentration of 10 and 50 while BT with BR treatment decreased DNA breakage. No genotoxicity was observed by BR($25{\sim}50{\mu}g/mL$) treatment alone on DNA breakage. Since BT can induce DNA damage through the generation of reactive oxygen species(ROS), we examined the level of ROS in human lymphocytes treated with BT and/or BR using DCF-DA, ROS-sensitive probe. The generation of ROS in BT-treated cells was also observed, and BR addition inhibited the level of BT-induced DNA damage. Conclusions : From above results it is suggested that BR could protect the cell and DNA from pro-oxidant effect by ROS by BT

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.6
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• pp.1485-1496
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• 2006

Various kinds of related parameters on hypertension such as anti-oxygen effect, ACE, weight of body, hwart and kidney, blood pressure, heartbeat rates, contents of aldosterone, catecholamine, change rates, of plasma constituents, uric acid, BUN, creatinine were determined to verify the effects on hypertension by Kamisamul-tang (KSMT). And the results are concluded as follows. KSMT did not show any cytotoxicity at the range of concentration (1-250 ${\mu}g/m{\ell}$) on the human fibroblast cell (hFCs). KSMT decreased the production of reactive oxygen species (ROS) and DPPH generation depending on the concentration. KSMT significantly inhibited angiotensin converting enzyme(ACE) activity depending on the concentration compared with control. KSMT maintained body weight of body, heat and kidney nearly normal group in hypertensive rat induced by DOCA-salt. KSMT significantly blood pressure and heart beat rate compared with control in hypertensive rat induced by DOCA-salt. KSMT significantly decreased aldosterone, dopamine, norepineph- rine, epinephrine compared with control in hypertensive rat induced by DOCA-salt. KSMT significantly decreased the level of potassium and cloride compared with control wheareas increased that of calcium significantly in hypertensive rat induced by DOCA-salt. KSMT significantly decreased the level of uric acid and BUN compared with control in hypertensive rat induced by DOCA-salt. It is verified experimentally tat Kamisamultang(KMST) which has been used broadly as a clinical therapeutics in oriental medicine is effective for anti-hypertension mechanism. And it could be applied to develope the reliable prescriptions for anti-hypertension in the future.