• The Journal of Internal Korean Medicine
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• v.34 no.2
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• pp.134-146
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• 2013

Objectives : Auklandia Lappa (ALE) is one of the herbs used frequently to treat abdominal pain and diarrhea and reported anti-inflammatory activity by suppressing proinflammatory cytokines. This study was designed to investigate whether ALE could show protective activities on experimental colitis induced by dextran sulfate sodium (DSS) models. Methods : Colitis was induced by DSS in Balb/c mice. ALE 10, 30, 100 and 300 mg/kg were orally administered twice a day for 7 days in DSS model. Mice weight was measured daily. Scoring of clinical findings was measured every other day. Colon length, edema, fecal blood and histological damages were assessed at day 7 in DSS model. In histological analysis, we checked cryptal glands, surface epithelium, submucosa, transmural, stroma and scored degree of inflammatory cell damage by modified histological scoring. We also calculated cytokines concentrations including IFN-${\gamma}$, TNF-${\alpha}$, IL-6, IL-$1{\beta}$, IL-17, IL-23, IL-10 and TGF-${\beta}1$ by Biometric Multiplex Cytokine Profiling method. Results : ALE showed the protective effects on DSS-induced experimental colitis. ALE inhibited shortening of colon length and histological damages of colon does-dependently, but it did not inhibit weight loss. ALE also inhibited IFN-${\gamma}$ and IL-6 expression, and upregulated cytokines (IL-10, TGF-${\beta}1$) related to regulatory T cell differentiation and proliferation. Conclusions : The current results demonstrate the clinical utility of ALE in traditional medicine and indicate the possibility of potent drug development of inflammatory bowel diseases from natural products. Further investigations for exact mechanisms will be needed.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3137-3140
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• 2015

Objective: To explore the immune reconstitution of $CD4^+T$ cells after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and its relationship with invasive fungal infection (IFI) in patients with hematological malignancies. Materials and Methods: Forty-seven patients with hematological malignancies undergoing Allo-HSCT in Binzhou Medical University Hospital from February, 2010 to October, 2014 were selected. At 1, 2 and 3 months after transplantation, the immune subpopulations and concentration of cytokines were assessed respectively using flow cytometry (FCM) and enzyme linked immunosorbent assay (ELISA). The incidence of IFI after transplantation and its correlation with immune reconstitution of $CD4^+T$ cells were investigated. Results: The number of $CD4^+T$ cells and immune subpopulations increased progressively after transplantation as time went on, but the subpopulation cell count 3 months after transplantation was still significantly lower than in the control group (p<0.01). In comparison to the control group, the levels of interleukin-6 (IL-6) and IL-10 after transplantation rose evidently (p<0.01), while that of transforming growth factor-${beta}$ (TGF-${beta}$) was decreased (p<0.01). There was no statistically significant difference level of interferon-${\gamma}$ (IFN-${\gamma}$) (p>0.05). The incidence of IFI was 19.2% (9/47), and multivariate logistic regression revealed that IFI might be related to Th17 cell count (p<0.05), instead of Th1, Th2 and Treg cell counts as well as IL-6, IL-10, TGF-${beta}$ and IFN-${\gamma}$ levels (p>0.05). Conclusions: After Allo-HSCT, the immune reconstitution of $CD4^+T$ cells is delayed and Th17 cell count decreases obviously, which may be related to occurrence of IFI.

• Journal of Korean Medicine Rehabilitation
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• v.26 no.3
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• pp.31-49
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• 2016

Objectives The study was designed to evaluate the healing effects of Joaguihwan (JGH) extract on Anti-oxidation, Anti-inflammatory in RAW 264.7 Cells and factors related with bone metabolism in skull fractured Rat. Methods The fracture healing effect of JGH was measured by scavenging activities of1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) and nitric oxide (NO) in RAW 264.7 cells. The inhibitory effect against the production of inflammatory mediators including interleukin-$1{\beta}$ (IL-$1{\beta}$), interleukin-6 (IL-6), tumor necosis factors-${\alpha}$ (TNF-${\alpha}$) expression was inhibited in RAW 264.7 cells was experimented using JGH. The effects of JGH on healing fractured rats was measured by osteocalcin, calcitonin, CTXII, TGF-${\beta}$, BMP-2, Insulin, ALP in the serum. and was checked every 3 weeks from 0 week to 6week using x-ray. Results 1. DPPH free radica and ABTS scavenging activity of JGH were increased according to concentration of JGH in RAW 264.7 Cells. 2. In the experiment, NO, IL-$1{\beta}$, IL-6, TNF-${\alpha}$ all showed decrease, in general. Especially NO and IL-$1{\beta}$ showed significantly decrease at a concentration of 10, 100 (${\mu}g/ml$). 3. In the production of osteocalcin in the serum, JGH 200, 400 mg/kg experimental group showed significant increased effect at 2 weeks. 4. In the production of calcitonin in the serum. JGH 200 mg/kg experimental group showed significant increased effect at 4, 6 weeks. JGH 400 mg/kg experimental group showed significant increased effect at 2, 4, 6 weeks. 5. In the production of CTX, TGF-${\beta}$, BMP-2 in the serum, experimental group showed increased effect. but no significant effect. 6. In the production of insulin in the serum. JGH 200, 400 mg/kg experimental group showed significant decrease effect at 2, 4, 6 weeks. 7. In the production of ALP in the serum. JGH 200 mg/kg experimental group showed significant increased effect at 2, 4, 6 weeks. JGH 400 mg/kg experimental group showed significant increased effect at 4, 6 weeks. 8. In the change of X-ray, the experimental group showed better healing effects on skull fractured rats than control group. Conclusions From above results, JGH showed healing effect on Anti-oxidation, Anti-inflammatory in RAW 264.7 Cells, factors related with bone metabolism in the serum of skull fractured rat and x-ray, which is expected to be applied in clinics.

• The Journal of Dong Guk Oriental Medicine
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• v.7 no.2
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• pp.155-162
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• 1999

Euonymus alatus(Thunb.) Sieb has been used for cancer theraphy such as Liver cancer, esophagus cancer, stomach cancer, and uterine cancer in folk. Eupolyphaga simemsis(ES) extracted from Euonymus alatus(Thunb.) Sieb increases HDL-C/TC ratio and LCAT activity. TGF-${\beta}$ and Insulin has been Knoen as factors to induce the supression of proliferation of Hep3B, Human hepatoblastoma cell. Plasma HDL3-C involved in carbohydrate methabolism in the liver was maintained in low level by Euonymus alatus(Thunb.) Sieb. The low level of plasma HDL3-C suppresses the transition from normal liver to Fat liver. Finally, this resuly in suppression of cancer in liver. In this study, Euonymus alatus(Thunb.) Sieb showed higher cell toxicity in hepatoblastoma cell(Hep3B) compared to the uterine cancer cell(HeLa). This means Euonymus alatus(Thunb.) Sieb seems not to affect in the all kinds of cancer. In future, we will study whether Euonymus alatus(Thunb.) Sleb have an effect on the liver cancer induced by virus and hepatocellular carcinoma. Also, the mechanims of suppression of cell proliferation in HCC need to investigated.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.7
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• pp.980-987
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• 2008

The objective of this study was to investigate the effects of cell status of BOEC on development of bovine IVM/IVF embryos and gene expression in BOEC before or after culturing of embryos. The developmental rates beyond morula stage in the BOEC co-culture group was significantly higher than in the control group (p<0.05). In particular, blastocyst production in the BOEC co-culture group (28.3%) was dramatically increased compared with the control group (7.2%). In the in vitro development of bovine IVM/IVF embryos according to cell status, the developmental rates beyond morula stage in the primary culture cell (PCC) co-culture group were the highest of all experimental groups. Expression of genes related to growth (TGF-${\beta}$ EGF and IGFBP), apoptosis (Bax, Caspase-3 and p53) and antioxidation (CuZnSOD, MnSOD, Catalase and GPx) in different status cells of BOEC for embryo culture was detected by RT-PCR. While EGF gene was detected in isolated fresh cells (IFC) and PCC, TGF-${\beta}$ and IGFBP were found in IFC or PCC after use in the embryo culture, respectively. Caspase-3 and Bax genes were detected in all experimental groups regardless of whether the BOEC was used or not used in the embryo culture. However, p53 gene was found in IFC of both conditions for embryo culture and in frozen/thawed culture cells (FPCC) after use in the embryo culture. Although antioxidant genes examined were detected in all experimental groups before using for the embryo culture, these genes were not detected after use. This study indicated that the BOEC co-culture system used for in vitro culture of bovine IVF embryos can increase the developmental rates, and cell generations and status of BOEC might affect the in vitro development of bovine embryos. The BOEC monolayer used in the embryo culture did not express the growth factors (TGF-${\beta}$ and EGF) and enzymatic antioxidant genes, thereby improving embryo development in vitro.

• Journal of the korean academy of Pediatric Dentistry
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• v.37 no.3
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• pp.275-287
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• 2010

Deep caries may induce pulpitis and the pulpal tissue interacts with microbial invasion. The immune response to protect the pulpal tissue can be mediated by cellular signal molecules produced by the pulpal cells. The understanding of these processes is important to find future therapeutic method for the diseased pulp. The pulp tissue from sound teeth was set as control group (n=30) and the pulp tissue from decayed teeth was set as test group (n=30). Total RNA was extracted from the pulp of each group and it was used for cDNA microarray and reverse transcriptase-polymerase chain reaction(RT-PCR). The expression of TGF-${\beta}1$ was studied by immunohistochemistry. The results were as follows: 1. cDNA microarray analysis identified 520 genes with 6-fold or greater difference in expression level with 143 genes more abundant in health and 377 genes more abundant in disease. 2. The RT-PCR analysis was done for randomly selected 14 genes and the results supported the result of cDNA microarray assay. 3. TGF-${\beta}1$ was highly expressed in the carious pulp and it was found in odontoblast by immunohistochemistry. In conclusion, many cytokines were found to be significantly changed their expression in the diseased pulp(/M/>1.6).

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.5
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• pp.1127-1134
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• 2007

The study was designed to investigate the mechanism of Patholoobi Caulis freeze dried powder (PCF) on the regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP) in normal rats and cytokines production ($IL-1{\beta}$, $TNF-{\alpha}$, IL-10, $TGF-{\beta}$) in cerebral ischemic rats. The results in normal rats were as follows ; Increase of PCF-induced rCBF was significantly inhibited by pretreatment with methylene blue (10 ${\mu}g/kg$, I.p.), an inhibitor of guanylate cyclase, and was inhibited by indomethacin (1 mg/kg, i.p.), an inhibitor of cyclooxygenase. Increase of PCF-induced MABP was decreased by pretreatment with methylene blue, but was increased by indomethacin. These results suggested that the mechanism of action PCF was mediated by cyclic 3',5'-guanosine monophosphate. The results in cerebral ischemic rats were as follows ; In cytokine production in serum from femoral arterial blood 1 hr after middle cerebral arterial occlusion, PCF (10 mg/kg. i.p.) significantly decreased $IL-1{\beta}$ and $TNF-{\alpha}$ production, and increased IL-10 production compared with control group. In cytokine production in serum from femoral arterial blood 1 hr 1 hr after reperfusion, PCF (10 mg/kg, i.p.) significantly decreased $IL-1{\beta}$ production, and incresed IL-10 production compared with control group. These results suggested that PCF was significantly and stably increased regional cerebral blood flow by inhibiting $IL-1{\beta}$ production, and by accelerating IL-10 production.

• Journal of Korean Medicine Rehabilitation
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• v.28 no.1
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• pp.1-17
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• 2018

Objectives The purpose of this study was to evaluate the effect of Jeopgolsan (JGS) extract on anti-oxidant, anti-inflammatory activities in RAW 264.7 cells and on factors related with fracture healing in skull fractured rat. Methods Experimental animals were divided into four groups: normal group without any treatment (Normal), contral group were treated orally with distilled water (Control), Experimental group were treated orally with JGS at a concentration of 200 mg/kg/day (JGS 200) and Experimental group were treated orally with JGS at a concentration of 200 mg/kg/day (JGS 400). Rats in each group except the normal group were induced fractures in the skull. The 1,1-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) radical scavenging activity were measured to evaluate antioxidant activity. The production of nitric oxide (NO), $interleukin-1{\beta}$ ($IL-1{\beta}$), interleukin-6 (IL-6) and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) in the RAW 264.7 cells were measured to evaluate anti-inflammatory activity. The production of osteocalcin calcitonin, carboxy-terminal telepeptides of type II collagen (CTX II), transforming growth $factor-{\beta}$ ($TGF-{\beta}$), bone morphogenetic protein-2 (BMP-2), Insulin and alkaline phosphatase (ALP) in serum of rats were measured to evaluate the effects of fracture healing at 0, 2, 4, and 6th week. X-rays were taken every 3 week from 0 to 6th week to evaluate fracture healing effect. Results 1. No cytotoxicity was observed. 2. DPPH and ABTS radical scavenging activity were increased in a concentration dependent manner, indicating anti-oxidant effect. 3. NO, $IL-1{\beta}$, IL-6, and $TNF-{\alpha}$ were not significantly changed, indicating no anti-inflammatory effect. 4. Osteocalcin, Calcitonin, $TGF-{\beta}$ and ALP were significantly increased in the experimental groups. 5. CTX II, insulin were significantly decreased in the expermental groups. 6. Radiologic examination showed that union of fracture was promoted. Conclusions From above results, JGS showed significant results in factors related with fracture healing and radiologic examination. Threfore, JGS is expected to be effective in the treatment of fracture.

• Biomedical Science Letters
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• v.19 no.3
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• pp.195-205
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• 2013

Obesity may cause metabolic syndrome and adult diseases. This study was undertaken to investigate the ameliorative or useful effects of beanleaves on inflammation and liver damage in obese rat models. Rats were divided into three groups: a control group (normal diet, n=6), a fat diet group (45%-fat diet, n=7), and a bean leaf group (45%-fat+Korean bean leaves diet, n=7). Body weights in the bean leaf group were lower than those of the fat group (P<0.05). Serum tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and prostaglandin $E_2$ ($PGE_2$) concentrations were lower in both the control and bean leaf groups than in the fat group (P<0.001). TNF-${\alpha}$ concentrations in the bean leaf group were slightly higher than in the control group but statistically significant (P<0.05). The bean leaf group histologically exhibited lower fatty degeneration, spotty necrosis, and leukocyte infiltrations in hepatic tissues than those of the fat group. In the homogenized liver tissues, the cyclooxygenase-2 (COX-2) gene was only expressed in the fat group. The gene expression levels of hepatic TNF-${\alpha}$, inducible nitric-oxide synthase, peroxiome proliferator-activated receptor-${\alpha}$ (PPAR-${\alpha}$), poly (ADP-ribose) polymerase (PARP), and transforming growth factor-${\beta}1$ (TGF-${\beta}1$) were weaker in the bean leaf group than in the fat group. These results suggest that adding bean-leaves to the diet may ameliorate obesity-induced systemic inflammation and liver damage and that bean leaves may be a useful food for preventing obesity and thereby metabolic syndrome and adult diseases.

• BMB Reports
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• v.39 no.6
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• pp.649-655
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• 2006

The NSAID activated gene (NAG-1), a member of the TGF-$\beta$ superfamily, is involved in tumor progression and development. The over-expression of NAG-1 in cancer cells results in growth arrest and increase in apoptosis, suggesting that NAG-1 has anti-tumorigenic activity. This conclusion is further supported by results of experiments with transgenic mice that ubiquitously express human NAG-1. These transgenic mice are resistant to the development of intestinal tumors following treatment with azoxymethane or by introduction of a mutant APC gene. In contrast, other data suggest a pro-tumorigenic role for NAG-1, for example, high expression of NAG-1 is frequently observed in tumors. NAG-1 may be like other members of the TGF-$\beta$ superfamily, acting as a tumor suppressor in the early stages, but acting pro-tumorigenic at the later stages of tumor progression. The expression of NAG-1 can be increased by treatment with drugs and chemicals documented to prevent tumor formation and development. Most notable is the increase in NAG-1 expression by the inhibitors of cyclooxygenases that prevent human colorectal cancer development. The regulation of NAG-1 is complex, but these agents act through either p53 or EGR-1 related pathways. In addition, an increase in NAG-1 is observed in inhibition of the AKT/GSK-$3{\beta}$ pathway, suggesting NAG-1 alters cell survival. Thus, NAG-1 expression is regulated by tumor suppressor pathways and appears to modulate tumor progression.