• 셀메드
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• 제3권2호
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• pp.15.1-15.5
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• 2013

Previous reports showed that Compound Astragalus and Salvia miltiorrhiza extract (CASE), which was mainly composed of astragalosides, astragalus polysaccharide and salvianolic acids, inhibited hepatic fibrosis by mediating transforming growth factor-${\beta}$ (TGF-${\beta}$)/Smad signaling. Our aim was to examine the effects of CASE on D-galactosamine (D-GalN) treated liver injury in mice and carbon tetrachloride ($CCl_4$)-induced liver fibrosis in rats. CASE was administered to mice with D-GalN-induced liver injury and to rats with $CCl_4$-induced liver fibrosis, respectively. Liver injury was routinely evaluated by relative liver weight, serum levels of ALT, AST, hyaluronic acid (HA), hepatic malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, hydroxyproline (HYP) and histopathologic changes. Treatment of mice with CASE (60, 120, and 240 mg/kg, ig) significantly lowered ALT, relative liver weight, and MDA levels when compared with D-GalN treated mice. CASE (120, 240 mg/kg) significantly lowered ALT, AST, HA, HYP, and MDA levels against $CCl_4$ treated rats. Decreased SOD level was reversed with CASE treatment. Upon histopathological examination, CASE treatment had significantly inhibitory effect on the progression of hepatic fibrosis in rats. These results indicate that CASE might be effective in treatment and prevention of acute and chronic hepatic injury due to its antioxidant activity.

• 약학회지
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• 제50권6호
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• pp.358-366
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• 2006

The aim of this study was to investigate the protective effects of glycynhizin, active glycosides of Glycyrrhizae Radix, and baicalin, bioactive flavonoid isolated from Scutellariae Radix, on hepatocyte injury induced by carbon tetrachloride(CCl$_4$, 10 mM), tert-butyl hydroperoxide (TBH, 0.5 mM), and D-galactosamine (GaIN, 30 mM). Primary cultures of rat hepatocyte (18 hr cultured) were treated with CCl$_4$, TBH, or GaIN and various concentrations (0.1, 1, 10, and 100 ${\mu}$M) of glycyrrhizin or baicalin. Activity was accessed by determining the release of lactate dehydrogenase (LDH) and aminotransferses. CCl$_4$ significantly increased the levels of LDH, alanine aminotransferase (ALT), and aspartate aminotransferase(AST) and these increases were prevented by baicalin concentrations of 0.1,1, and 100 ${\mu}$M. The increases in ALT and AST levels were reduced by glycyrrhizin concentration of 100 ${\mu}$M. The level of LDH was markedly increased by TBH, and this increase was reduced by both glycyrrhizin and baicalin. ALT and AST levels were increased by TBH, which were prevented by glycynhizin and bacalin, respectively: GaIN markedly increased the levels of LDH, ALT and AST These increases was significantly reduced by both glycyrrhizin and baicalin. These results suggest that glycynhizin and baicalin possess the hepatoprotective activity.

• Biomolecules & Therapeutics
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• 제12권3호
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• pp.133-137
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• 2004

Present review is built on base of research work on Ganoderma lucidum in our laboratory. A great deal of experimental evidence has suggested that the pharmacological activities of Ganoderma lucidum (Lingzhi) are related to anti-oxidative and free radical scavenging activity. The anti-oxidative and free radical scavenging effects of polysaccharides and triterpenoids isolated from Ganoderma lucidum in different oxidative injury models including tert-butylhydroperoxide (tBOOH)- damaged mice peritoneal macrophages, alloxan-induced diabetes, experimental liver injury models induced by carbon tetrachloride (CCl4), D-galactosamine (DGal) and Bacillus Calmette-Guerin (BCG) plus lipopolysaccharides (LPS) were investigated. It is also demonstrated that Lugu lingzhi, one of Ganoderma product, significantly inhibited LDL oxidation mediated by endothelial cells and decreased monocyte adhesion to endothelial cell (EC) induced by Oxidative low-density lipoprotein (ox-LDL) and advanced glycation endproducts (AGE). Lugulingzhi-treated serum could markedly inhibit the expression of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-l) induced by ox-LDL and AGE.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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• pp.179-179
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• 1998

We previously reported the hepato-protective effect of butanol soluble fraction of methanolic extract of Carthamus tinctorius L. Semen on carbon tetrachloride induced hepatotoxicity. In this study, the active component from the butanol soluble fraction was isolated by column chromatographic separation using Silica gel and Sephadex LH -20 and identified by spectroscopic methods such as Mass, $^1$H - NMR and $\^$13/C-NMR. The hepato-protective effect of the isolated active component on the CCl$_4$-induced liver damaged rats has been evaluated by performing blood chemical analysis and biotransformational enzyme analysis.

• Bulletin of the Korean Chemical Society
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• 제1권3호
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• pp.75-78
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• 1980

The interactions of iodine with toluidines (o-, m-, and p-) and N-methyltoluidines (o-, m-, and p-) in $CCl_4$ solution have been investigated through spectrophotometric measurements. The results indicate that toluidines and N-methyltoluidines form the one-to-one charge-transfer complexes with $I_2$ in solution. By comparing the values of the formation constants of the complexes, it is concluded that the relative stabilities of the $I_2$-amine complexes decrease in the following orders: p-toluidine >m-toluidine >aniline >o-toluidine, N-methyl-p-toluidine >N-methyl-m-toluidine >N-methylaniline >N-methyl-o-toluidine, N-methyltoluidines >toluidines. These results can be explained by the electron-releasing character and the steric effect of methyl group in the amine molecules.

• 한국식품위생안전성학회지
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• 제26권3호
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• pp.235-241
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• 2011

아직 분명히 규명되지 않은 부분이 많지만, 신선초가 다양한 측면에서 건강증진 효과가 있다고 믿어져 왔고 따라서 일반인들이 지금까지 사용해 오고 있다. 이 연구에서는 신선초의 메타놀 추출물을 투여한 후, 전형적인 간독성 유발물질인 갈락토사민과 사염화탄소를 투여한 랫드에서 일반적 간독성지표와 지질대사능 지표를 측정함으로써 간장 보호작용이 있는지 시험하였다. 신선초를 독성유발전 7일간 매일 1회씩 200 및 500mg/kg의 용량으로 경구투여 하고, 간독성물질을 복강내로 투여 한 후 독성유발 24시간에 혈장과 간장조직에 대한 분석을 수행하였다. 시험한 두 용량(200 및 500 mg/kg)은 갈락토사민에 의해 유발된 지질과 산화물 증가, 혈장 AST 및 ALT 활성의 증가를 감소시켰다. 또한 신선초 500mg/kg은 갈락토사민이 유발한 혈장 중성지질, 총 콜레스테롤 및 저밀도지단백 콜레스테롤의 농도 증가현상을 감소시켰다. 갈락토사민에 의해 유발된 독성에 대한 효과와는 달리, 사염화탄소로 유발된 AST, ALT 및 과산화지질의 증가현상이 신선초 전투여에 의해 더욱 증가하였다. 이 결과는 갈락토사민에 의한 독성을 신선초 전투여가 감소시킬 수 있지만, 반대로 사염화탄소 유발 독성은 더 악화시킴을 의미한다. 신선초의 사염화탄소 유발 간독성 증강효과에 대한 기전을 이해하기 위해 신선초를 투여한 랫드의 간장내 aninline hydroxyiase의 활성을 측정하였다. 그 결과 사염화탄소가 간독성을 발휘하는 데에 필요한 조건인 대사체로의 변환을 매개하는 이 효소의 간장내 활성이 증가함을 관찰하였다. 종합적으로 신선초가 간장보호효과를 발휘하지만 간독성이 어떤 독소에 의해 유발되었느냐에 따라 향상 보호효과가 있지는 않음을 의미한다.

• 사상체질의학회지
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• 제15권1호
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• pp.90-108
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• 2003

Osuyubujaijung-tang(OBT) and Sipyimiguanjung-tang(SGT) has been developed as prescriptions for the Soyeumin constitution. The hepatoprotective effect of the water extract of Osuyubujaijung-tang(OBT) and Sipyimiguanjung-tang(SGT) was investigated against carbon tetrachloride (CCl4)-induced hepatic damage. A single intra-peritoneal injection of CCl4 produced liver damage in rats as manifested by the significant rise of aspartate aminotransferase(AST), alanine aminotransferase(ALT), and alkaline phosphatase(ALP) in serum as compared to those of untreated normal group. Pretreatments of rats with Osuyubujaijung-tang(OBT) and Sipyimiguanjung-tang(SGT) 500 mg/kg for 7 days) were significantly reduced AST, ALT, and ALP levels compared with CCl4-treated control group. Treatment of rats with CCl4 led to significantly increase in lipid peroxidation and significantly decrease in cytochrome P450 and P450 reductase. The oral administration of Osuyubujaijung-tang(OBT) and Sipyimiguanjung-tang(SGT) water extract significantly inhibited the accumulation of microsomal thiobarbituric acid reactive substance (TBARS) and increased the cytochrome P450 and P450 reductase activity. All these biochemical alterations resulting from CCl4 administration were inhibited by the pretreatment with Osuyubujaijung-tang(OBT) and Sipyimiguanjung-tang(SG1) extract. These results suggest that Osuyubujaijung-tang(OBT) and Sipyimiguanjung-tang(SGT) water extract can be useful as a hepatoprotective agent. And the effect of NO modulation by NO synthesis or precursors, and Osuyubujaijung-tang(OBT) and Sipyimiguanjung-tang (SGT) water extract was researched on chronic liver damage induced by CCl4 administration. It was observed that endogenous NO protected the liver from lipid peroxidation, fibrosis, and damage. Osuyubujaijung-tang(OBT) and Sipyimiguanjung-tang(SGT) water extract showed the hepatoprotective effect on the chronic liver cirrhosis model and relationship with NO modulation.

• 대한수의학회지
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• 제38권4호
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• pp.918-928
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• 1998

The present study was done with two aims. First, to evaluate the radiographic measurements of liver volumes in normal and hepatomegaly dogs induced by carbon tetrachloride. Second, to investigate quantitative tissue echo pattern by ultrasonography. Gray level histogram of the normal liver and the kidney were estimated with carbon tetra-chloride intoxication. In normal, r-square for liver volume to body weight was 0.93372, and this showed direct linear regression. Gray level histograms of the normal liver and the kidney were $19.150{\pm}2.490$(mean${\pm}$SD) and $13.175{\pm}2.686$(mean${\pm}$SD) respectively(p < 0.01). Liver parenchymal echogenicity was more hyperechogenic than kidney cortex echogenicity. Liver/Kidney ratio was $1.504{\pm}0.313$ and it can be used relative comparison of liver and kidney parenchymal echogenicity. In carbon-tetrachloride($CCl_4$) intoxication, changes of liver volume appeared to increase up to 24 hours after administration (p < 0.05), and decreased gradually to normal level after 2~5 days. Gray level histogram of liver parenchyma decreased up to 24hours (p < 0.01) after intoxication and then gradually increased to normal level. But that of kidney cortex had no significant change. Liver/Kidney ratio also decreased by 2 days(p < 0.01) and then gradually increased to normal level. On histopathologic features of hepatic tissues in carbon tetrachloride intoxication, both coagulative necrosis of hepatic cell and hemorrhage of centrilobular & midzonal area were identified. Conclusively, plain radiography is a useful diagnostic method for evaluating liver volume in mild hepatomegaly. Especially, it is considered that an adequate numerical processing of the liver length, depth and thoracic width and depth measurement would be helpful. Using gray level histogram, ultrasonographic evaluation was useful objective methods in early diagnosis of diffuse hepatic disease.

• 동의생리병리학회지
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• 제17권1호
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• pp.118-122
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• 2003

Oxidative stress and its consequent lipid peroxidation exert harmful effects, which have been currently involved in the generation of carbon tetrachloride (CCl₄)-induced fibrosis(cirrhosis). In this study, it was investigated whether dried extract of 田螺(Concha Cipangopaludinae; CC) has liver functional improvement, antioxidative and antifibrotic effect in rats those were induced liver fibrosis by CCl₄ administration. The female Sprague-Dawley rats were divided into 3 groups(Normal, AC, AC-CC) and were observed in 6 weeks. Except for normal group, liver fibrosis(cirrhosis) in rats were developed by CCl₄ administration(0.8 ㎖/rat/week). And the rats were treated with prepared CC(p. o. 2 ㎖/day/rat). At the time of sacrifice, the liver, kidney and spleen were weighed and the ratio of organ weight/body weight was calculated. The MDA, hyp and biochemical parameters(AST, ALT, ALP, t-bili) were measured in sera and liver tissue of rats. The strong yellow color of urine was observed in all CCl₄-treated group compared with normal group, but jaundice didn't appear in CCl₄-treated group. The mortality of CCl₄-treated group is very low(<13%) during 6 weeks of observation time. The ratio of liver/body as well as the weight of liver in CCl₄-treated rats significantly increased compared with that in normal group(p<0.001). The level of clinical parameters in sera of all liver fibrosis(cirrhosis) developed rats were significantly higher than that of normal group(p<0.001-0.05). Especially the value of BUN, ALP, t-bilirubin in AC-CC group showed 20.9%, 19.6%, 47.9% lower than that in AC group. The content of hyp in CCl₄-treated rats was significantly higher than normal group(p<0.001～<0.05), and showed 12.2% lower value in the AC-CC group than AC group(p<0.05). The production of lipid peroxidation(MDA) in sera and liver tissue significantly increased under the fibrotic(cirrhotic) condition(p<0.001～<0.05). Especially the MDA value of AC-CC group in sera significantly 46.5% decreased compared with that of AC group(p<0.05), and the MDA value of AC-CC in liver tissue showed 21.4% lower than that of AC group. Concha Cipangopaludinae can be improved hepatic function, and maybe have effect of liver protection, antioxidation and antifibrosis.

• Biomolecules & Therapeutics
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• 제29권2호
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• pp.175-183
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• 2021

The mitogen-activated protein kinase (MAPK) pathway controls intestinal epithelial barrier permeability by regulating tight junctions (TJs) and epithelial cells damage. Heme oxygenase-1 (HO-1) and carbon monoxide (CO) protect the intestinal epithelial barrier function, but the molecular mechanism is not yet clarified. MAPK activation and barrier permeability were studied using monolayers of Caco-2 cells treated with tissue necrosis factor α (TNF-α) transfected with FUGW-HO-1 or pLKO.1-sh-HO-1 plasmid. Intestinal mucosal barrier permeability and MAPK activation were also investigated using carbon tetrachloride (CCl4) administration with CoPP (a HO-1 inducer), ZnPP (a HO-1 inhibitor), CO releasing molecule 2 (CORM-2), or inactived-CORM-2-treated wild-type mice and mice with HO-1 deficiency in intestinal epithelial cells. TNF-α increased epithelial TJ disruption and cleaved caspase-3 expression, induced ERK, p38, and JNK phosphorylation. In addition, HO-1 blocked TNF-α-induced increase in epithelial TJs disruption, cleaved caspase-3 expression, as well as ERK, p38, and JNK phosphorylation in an HO-1-dependent manner. CoPP and CORM-2 directly ameliorated intestinal mucosal injury, attenuated TJ disruption and cleaved caspase-3 expression, and inhibited epithelial ERK, p38, and JNK phosphorylation after chronic CCl4 injection. Conversely, ZnPP completely reversed these effects. Furthermore, mice with intestinal epithelial HO-1 deficient exhibited a robust increase in mucosal TJs disruption, cleaved caspase-3 expression, and MAPKs activation as compared to the control group mice. These data demonstrated that HO-1-dependent MAPK signaling inhibition preserves the intestinal mucosal barrier integrity by abrogating TJ dysregulation and epithelial cell damage. The differential targeting of gut HO-1-MAPK axis leads to improved intestinal disease therapy.