• 동의생리병리학회지
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• 제31권6호
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• pp.328-333
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• 2017

Desomodii Herba (DH) has been shown to exhibit pharmacologyical activities, such as increase myocaridal contraction and secretion of hepatic bile. DH is used to reduce pain caused by rheumatoid arthritis(RA) in Korean medicine. However, the DH exact(DHE) effect and mechanism on rheumatoid arthritis are unknown. In this study, we aimed at the inhibitory effect of DHE on rheumatoid arthritis, and investigated the effect in collagen-induced mice arthritis model and TNF-${\alpha}$ induced MMP-1 and MMP-3 expression including the molecular basis in rheumatoid arthritis synovial fibroblasts (RASFs).The effect of DHE on RA was measured by clinical scoring system. In RASFs, expression of MMP-1 and MMP-3 was assessed by Western blotting and real-time PCR. Also, Western blotting used to evaluate the phosphorylation levels of p38, ERK and JNK and activation of NF-${\kappa}B$ and AP-1. Our results showed that DHE reduced collagen-induced arthritis in mice. DHE inhibits TNF-${\alpha}$ induced MMP-1 and MMP-3 expression and mRNA levels in RASFs. The inhibitory effect of DHE was mediated by the inhibition of the AP-1/JNK signaling pathway. Taken together, our results suggest that the DHE may have preventive potential for rheumatoid arthritis.

• Asian-Australasian Journal of Animal Sciences
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• 제10권3호
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• pp.260-264
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• 1997

This study was conducted with adult cockerels to determine whether dietary RNA affects feed intake and renal weight and function, and if the responses are similar to dietary adenine. Chickens were ad libitum fed a RNA diet (100 g/kg) or an adenine diet (9.1 g/kg) for 14 d and catheterized in right jugular vein, hepatic portal vein and both urethers, and saline together with para-amino hippuric acid and sodium thiosulfate was continuously infused into them to evaluate renal functions. Dietary RNA reduced feed intake and body weight, and dietary adenine increased kidney weight expressed as a proportion of body weight (P < 0.05). Feed intake and body weight on the adenine diet and kidney weight on the RNA diet showed similar though non significant tendencies. No calculi were detected in the kidney in chickens fed either the RNA or adenine diets. Plasma inorganic phosphate (IP), Ca and 1,25 $(OH)_2$ vitamin $D_3$ concentrations were increased by dietary RNA and adenine, although the increases of IP and Ca in adenine-fed chickens were not significant. Uric acid and urea concentrations in the blood plasma were unaffected by dietary RNA or adenine. Both dietary RNA and adenine increased renal blood flow rates 3.5-3.7 fold, renal plasma flow rates 3.4-3.7 fold and glomerular filtration rates (GFR) 2.9-3.0 fold (p < 0.01). Clearance of urea, IP and Ca were also enhanced by dietary RNA, but not by dietary adenine. However, neither RNA nor adenine affected uric acid clearance. Only IP clearance was significantly augmented at the glomerular level by dietary RNA (p < 0.05). Glomerular filtration of uric acid, urea, IP and Ca and reabsorption of urea, IP and Ca at the renal tubule were increased by dietary RNA and adenine (p < 0.05), whereas tubular secretion of uric acid was decreased by both dietary treatments. It is concluded that dietary adenine is effective in changing renal function and P and Ca metabolism in chickens.

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.747-752
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• 2013

Oncostatin M (OSM) is a multifunctional cellular regulator acting on a wide variety of cells, which has potential roles in the regulation of gene activation, cell survival, proliferation and differentiation. Previous studies have shown that OSM can induce morphological and/or functional differentiation and maturation of many tumor cells. However, the action of OSM on the induction of differentiation of human hepatocellular carcinoma (HCC) has not been reported. Here, we investigated the effects of different concentrations of OSM on human HCC cell line SMMC-7721 growth, proliferation, cell cycling, apoptosis and differentiation in vitro. Cell growth was determined via MTT assay, proliferation by cell cycle analysis, apoptosis by flow cytometry, morphology by transmission electronic microscopy, and cell function by detection of biochemical markers. Our results demonstrated that OSM strongly inhibited the growth of SMMC-7721 cells in a dose-dependent manner, associated with decreased clonogenicity. Cell cycle analysis revealed a decreased proportion of cells in S phase, with arrest at G0/G1. The apotosis rate was increased after OSM treatment compared to the control. These changes were associated with striking changes in cellular morphology, toward a more mature hepatic phenotype, accompanied by significant reduction of the expression of AFP and specific activity of ${\gamma}$-GT, with remarkable increase in secretion of albumin and ALP activity. Taken together, our findings indicate that OSM could induce the differentiation and reduce cell viability of SMMC-7721 cells, suggesting that differentiation therapy with OSM offers the opportunity for therapeutic intervention in HCC.

• 한국식품영양과학회지
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• 제35권10호
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• pp.1329-1335
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• 2006

AIDS로의 진행과정은 단순히 몇몇 기작에 의한 것이 아니라 여러 경로를 거쳐 발생하며 그 진행속도도 개개인에 따라 다양하게 나타나고 있다. 본 연구에서는 쥐 AIDS 모델을 이용하여 항산화호르몬으로 알려진 DHEAS의 면역조절 효과를 확인하고자 하였다. DHEAS의 투여는 LP-BM5 retrovirus 감염으로 인한 T와 B 임파구의 mitogenesis를 증가시켰으며 Th1/Th2 type cytokines의 발현에도 영향을 미쳤는데 주로 전사수준에서 작용한 것으로 생각된다/ 또한 retrovirus 감염으로 인한 간조직의 지질과산화 유발을 억제하여 조직 내의 항산화제인 vitamin E의 함량을 유지시킴으로 NF-kB의 활성화를 통한 retrovirus의 복제를 억제시켜 Th1/Th2 type cytokines의 불균형적인 발현을 저해하였을 것으로 여겨진다. 따라서 쥐 AIDS모델에 있어서 DHEAS의 면역조절 효과를 확인한 본 연구는 향후 HIV감염 이후 AIDS로의 진행 과정 시 항산화제의 역할과 기작 규명에 대한 가능성을 제시할 수 있을 것으로 생각된다.

• Nutrition Research and Practice
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• 제3권1호
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• pp.23-30
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• 2009

The aim of this study was to examine the hypoglycemic effect of chlorella in 6 week-old type 2 diabetic Goto-Kakizaki (GK, n=30) rats and 6 week-old normal Wistar (n=30) rats. Animals were randomly assigned to 3 groups respectively, and were fed three different experimental diets containing 0%, 3% or 5% (w/w) chlorella for 8 weeks. In diabetic GK rats, the insulinogenic-indices were not significantly different among the groups. The concentrations of fasting plasma glucagon and hepatic triglyceride, and the insulin/glucagon ratios of the GK-3% chlorella and GK-5% chlorella groups were significantly lower than those of the GK-control group. The HOMA-index and the concentrations of fasting blood glucose and plasma insulin of the GK-3% chlorella and GK-5% chlorella groups were slightly lower than those of the GK-control group. In normal Wistar rats, the insulinogenic-indices were not significantly different among the normal groups, but that of the Wistar-5% chlorella group was slightly higher than the other groups. The concentrations of fasting blood glucose and plasma insulin, and the HOMA-index of the Wistar-5% chlorella group were a little higher, and the fasting plasma glucagon concentration and the insulin/glucagon ratio of the Wistar-5% chlorella group were significantly higher than those of the Wistar-control and Wistar-3% chlorella groups. In conclusion, this study shows that the glucose-stimulated insulin secretion was not affected by the intake of chlorella, which could be beneficial, however, in improving insulin sensitivity in type 2 diabetic GK and normal Wistar rats.

• International Journal of Oral Biology
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• 제45권4호
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• pp.190-196
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• 2020

Several factors, including genetic and environmental insults, impede protein folding and secretion in the endoplasmic reticulum (ER). Accumulation of unfolded or mis-folded protein in the ER manifests as ER stress. To cope with this morbid condition of the ER, recent data has suggested that the intracellular event of an unfolded protein response plays a critical role in managing the secretory load and maintaining proteostasis in the ER. Tauroursodeoxycholic acid (TUDCA) is a chemical chaperone and hydrophilic bile acid that is known to inhibit apoptosis by attenuating ER stress. Numerous studies have revealed that TUDCA affects hepatic diseases, obesity, and inflammatory illnesses. Recently, molecular regulation of ER stress in tooth development, especially during the secretory stage, has been studied. Therefore, in this study, we examined the developmental role of ER stress regulation in tooth morphogenesis using in vitro organ cultivation methods with a chemical chaperone treatment, TUDCA. Altered cellular events including proliferation, apoptosis, and dentinogenesis were examined using immunostaining and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. In addition, altered localization patterns of the formation of hard tissue matrices related to molecules, including amelogenin and nestin, were examined to assess their morphological changes. Based on our findings, modulating the role of the chemical chaperone TUDCA in tooth morphogenesis, especially through the modulation of cellular proliferation and apoptosis, could be applied as a supporting data for tooth regeneration for future studies.

• 대한약리학회지
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• 제17권1호
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• pp.17-25
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• 1981

No evidence has accumulated that lead compound is an essential component for biological function in animals. Lead is absorbed primarily through the epithelial mucosal cells in duodenum and the absorption can be enhanced by the substances which bind lead and increase its solubility. Iron, zinc and calcium ions, however, decrease the absorption of lead without affecting its solubility, probably by competing for shared absorptive receptors in the intestinal mucosa. Therefore, the absorption of lead is increased in iron deficient animals. Lead shows a strong affinity for ligands such as phosphate, cysteinyl and histidyl side chains of proteins, pterins and porphyrins. Hence lead can act on various active sites of enzymes, inhibiting the enzymes which has functional sulfhydryl groups. lead inhibits the activity of ${\delta}$-aminolevulinic acid dehydratase for the biosynthesis of hemoproteins and cytochrome, which catalyzed the synthesis of monopyrrole prophobilinogen from ${\delta}$-aminolevulinic acid. Accordingly lead decrease hepatic cytochrome p-450 content, resulting an inhibition of the activity of demethylase and hydroxylase in liver. Little informations are available on the effect of lead on digestive system although the catastrophic effects of lead intoxication are well documented. The present study was, therefore, attempted to investigate the effect of lead on pancreaticobiliary secretion in rats. Albino rats of both sexes weighing $170{\sim}230g$ were used for this study. The animals were divided into one control and three treated groups, i.e., control (physiologic saline 1.5ml/kg i.p.), lead acetate $(l0{\mu}mole/kg/day\;i.p.)$, $Pb(Ac)_2$ and EDTA$(each\;10{\mu}mole/kg/day\;i.p.)$, $Pb(Ac)_2$ and $FeSO_4(each\;l0{\mu}mole/kg/day\;hp)$. The pancreatico-biliary juice was collected under urethane anesthesia, and activities of amylase and lipase were determined by employing Sumner's and Cherry and Crandall's methods. The summarized results are follows. 1) In the experiment for acute toxicity of lead acetate, 20% of mortality was observed in rat treated with lead acetate as well as inhibition of the activity of amylase in the juice at the 3 rd day of the treatment. 2) No increases in body weight were observed in rats treated with lead acetate, while in control group the significant increases were observed. However, the body weights of animals were increased in the group lead acetate plus EDTA or $FeSO_4$. 3) Lead acetate decreased significantly the volume of pancreatico-biliary juice whereas additional treatment of EDTA and $FeSO_4$ prevented it. 4) Total activity of amylase was markedly reduced due to lead acetate treatment, but no change was showed following additional treatment with EDTA and $FeSO_4$. 5) No changes in the cholate and lipase output were observed in rats treated with lead acetate as compared with that of control rats. 6) Increase in bilirubin output in rats treated with lead acetate was shown on the 2nd and 3rd weeks treatment. 7) In the case of in vitro experiment, lead acetate also markedly inhibited release of amylase from pancreatic fragment. 8) Histologic finding indicated that acini vacuolation was induced in the pancreatic tissue of rat treated with lead acete. From the above results, it might be concluded that lead acetate decreases the volume of pancreatico-biliary secretion and inhibits the amylase activity, by acting directly on pancreatic cells.

• 한국식품영양과학회지
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• 제38권4호
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• pp.415-422
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• 2009

고 fructose 식이를 섭취시켜 제 2형 당뇨를 유발한 쥐에서 ZA의 섭취가 혈당 조절에 미치는 기전을 밝히고자 하였다. 4주 동안의 실험기간 중 Control군(normal chow diet), Fructose군(high-fructose diet)과 Fructose+ZA군(highfructose diet+ZA treatment) 간의 체중, 먹이 및 물의 섭취량에는 유의한 차이를 나타내지 않았다(p<0.05). 기저상태 (basal state)에서 혈장 포도당, 인슐린 농도 및 간의 포도당 생성률을 측정한 결과 Control군과 Fructose군 및 Fructose+ZA군 간의 차이를 나타내지 않았다. 인슐린 감수성을 알아보기 위한 hyperinsulinemic euglycemic clamp 실험에서 인슐린 농도와 포도당 농도는 군 간의 차이를 나타내지 않았다. 또한 인슐린 감수성 지표인 포도당 흡수(glucose uptake)에서도 역시 군 간의 차이를 발견하지 못하였다. 그러나 간의 인슐린 감수성 지표인 간의 포도당 생성률(HGO)에서는 Fructose군이 Control군에 비하여 유의적으로 증가되었고 (p<0.05), Fructose+ZA군이 대조군의 수준으로 감소되었다. 이것으로 미루어 볼 때 fructose 식이는 간에서 인슐린감수성을 감소시켰으나 당뇨는 유발되지 않았으며, ZA 섭취가 간의 포도당 생성률을 억제하는 것으로 보아 인슐린 감수성을 증가시키지만, 말초조직의 포도당 이용에는 영향을 미치지 않는 것으로 사료된다.

• Clinical and Experimental Pediatrics
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• 제48권11호
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• pp.1239-1243
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• 2005

목 적 : 체내에 축적된 철은 간에서 인슐린제거를 늦게 해 고인슐린혈증을 유발하며, 인슐린 작용을 저해시키고 이로 인해 당신생이 증가해 이차적으로 당뇨병을 유발할 수 있는 것으로 알려져 있다. 따라서 체내의 저장 철을 알 수 있는 가장 좋은 지표인 ferritin을 측정해 2형 당뇨병 발생과의 연관성을 조사하기 위한 연구를 시행하였다. 방 법 : 연세의료원에서 진료받고 있는 1형 당뇨 환자군 36명, 2형 당뇨 환자군 8명, 내당능 장애군 18명을 대상으로 하였으며, 2004년 학교 신체 검사에서 정상 대조군 29명을 선정하여, ferritin과 기타 혈청학적 및 임상적 검사를 실시하였다. 결 과 : 1) 정상대조군, 내당능 장애군, 2형 당뇨 환자군에서 평균 Log ferritin은 각각 $1.33{\pm}0.32$, $1.63{\pm}0.19$, $1.90{\pm}0.30$였으며 정상 대조군에 비해 내당능 장애군(P<0.01)과 2형 당뇨 환자군(P<0.01)에서 유의하게 증가되어 있었다. 2) Log ferritin과 각 변수인자와의 상관관계는 체질량 지수(P<0.01), 수축기 혈압(P<0.01), 공복시 혈당(P<0.01), 공복시 인슐린(P<0.01)과 유의한 관계를 보였다. 결 론 : 정상 대조군에 비해 내당능 장애군과 2형 당뇨 환자군에서 ferritin이 의미 있게 높았으며 ferritin의 증가는 인슐린 저항성과 2형 당뇨병 발생의 유발인자로서의 가능성을 시사한다.

• 대한한방소아과학회지
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• 제29권3호
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• pp.65-79
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• 2015

Objectives : In this study, effects of haepyoijintang (HIJ) on the increase in airway epithelial mucosubstances of rats and ATP-, PMA-, EGF- or TNF-${\alpha}$-induced MUC5AC mucin production and gene expression from human airway epithelial cells were investigated. Methods : Hypersecretion of airway mucus was induced by exposure of rats to $SO_2$ during 3 weeks. Effect of orally-administered HIJ during 2 weeks on increase in airway epithelial mucosubstances from tracheal goblet cells of rats was evaluated using histopathological analysis after staining the epithelial tissue with PAS-alcian blue. Possible cytotoxicity of HIJ was evaluated by examining the potential damage of kidney and liver functions by measuring serum GOT/GPT activities and serum BUN and creatinine concentrations of rats and the body weight gain during experiment, after administering HIJ orally. At the same time, the effect of HIJ on ATP-, PMA-, EGF- or TNF-${\alpha}$-induced MUC5AC mucin production and gene expression from human airway epithelial cells (NCI-H292) were investigated. Confluent NCI-H292 cells were pretreated for 30 min in the presence of HIJ and treated with ATP ($200{\mu}M$), PMA (10 ng/ml), EGF (25 ng/ml) or TNF-${\alpha}$ (0.2 nM) for 24 hrs, to evaluate the effect of HIJ both on ATP-, PMA-, EGF- or TNF-${\alpha}$-induced MUC5AC mucin production using enzyme-linked immunosorbent assay (ELISA) and on gene expression by the same inducers using reverse transcription-polymerase chain reaction (RT-PCR). Results : (1) HIJ decreased the amount of intraepithelial mucosubstances of trachea of rats. (2) HIJ did not show renal and hepatic toxicities and did not affect body weight gain of rats during experiment. (3) HIJ significantly inhibited ATP-, PMA-, EGF-, and TNF-${\alpha}$-induced MUC5AC mucin productions from NCI-H292 cells. (4) HIJ significantly inhibited ATP-, PMA-, EGF-, and TNF-${\alpha}$-induced MUC5AC mucin gene expression from NCI-H292 cells. Conclusions : The result from the present study suggests that HIJ might control the production and gene expression of airway mucin observed in various respiratory diseases accompanied by mucus hypersecretion and do not show in vivo toxicity to liver and kidney functions after oral administration. Effect of HIJ with their diverse components should be further investigated using animal experimental models that can reflect the pathophysiology of airway diseases through future studies.