• Korean Journal of Pharmacognosy
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• v.19 no.4
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• pp.270-277
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• 1988

Gamiinjinoryung-San is composed of eight crude drugs including Artemisiae capillaris Herba which is widely used for the treatment of acute jaundice, acute and chronic hepatitis at the Oriental hospital of Kyung-Hee Medical Center. This study was conducted to investigate the effects of water extract of Gamiinjinoryung-San on the liver function. The results obtained were as follows; the extract markedly reduced LDH and ALP activities, but slightly decreased GOT and GPT activities elevated with D-galactosamine in rat serum. The liver protective activities were shown in $CCl_4-intoxicated\;rats$. The extract prevented the prolongation of sleeping time in $CCl_4-intoxicated\;rats$. The bile flow and the biliary bile acid secretion were significantly increased in normal rats.

• Korean Journal of Veterinary Research
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• v.35 no.3
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• pp.481-488
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• 1995

In oriental folk medicine, Artemisia messes-schmidiana var viridis(Compositae) has been used for jaundice, hepatitis, diuretic and liver cirrhosis etc. 1-naphthylisothiocyanate(ANIT) has been used for more than 20 years as a model compound to study mechanisms of intrahepatic cholestasis in laboratory animals as rat and mouse. Various biochemical and morphological changes including biliary epithelial and parenchymal cell necrosis occur in the liver of animals treated with ANIT. The purposes of present study are to examine pharmacological effects of Artemisia messes-schmidiana var viridis water extract(AMWE) on alterations of secretion volume and total bile acids level in bile juice, and that of serum AST, ALT, ALP, bilirubin, and glucose levels in rat. AMWE stimulated bile secretion and recovered ANIT-induced cholestasis. Bile acid concentrations increased to more than 60% compared with normal by ANIT, which were returned toward normal value with AMWE treatment. Serum AST and ALT activities were increased by ANIT and yet which were significantly decreased with AMWE treatment. In addition, this effect was apparent in AMWE pretreatment group. Serum glucose levels were increased with AMWE and ANIT, while were decreased compared with control in AMWE posttreatment group. Increased serum total bilirubin contents and ALP activities by ANIT were significantly decreased with AMWE posttreatment. In conclusion, AMWE exerted bile acid-independent choleresis effect and then improved to normal conditions ANIT-induced cholestatic syndromes. Also, AMWE have protective and regenerative effect of hepatocytes in rat.

• Journal of the Korea Society of Computer and Information
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• v.21 no.12
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• pp.139-145
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• 2016

In this paper, we propose to evaluate the effect of Resistin-like molecule alpha (Retnla) on the expression of transporters involved in modulating concentrations of peripheral cholesterol and plasma high-density lipoprotein (HDL) cholesterol. High levels of blood cholesterol are a well-recognized risk factor for atherosclerosis and are eliminated via the process of reverse cholesterol transport (RCT). We recently showed that Retnla ameliorates hypercholesterolemia and atherosclerosis by increasing biliary cholesterol secretion, the final step of the process, in low-density lipoprotein receptor-deficient mice. However, the role of Retnla in HDL-mediated cholesterol efflux, initial step of RCT pathway, is not yet clear. To identify cholesterol transport genes regulated by Retnla, we performed an extensive microarray-based gene expression screen using livers from Retnla-overexpressing (Tg) mice and control animals. The most significant change in Retnla-Tg mice was an upregulation of ATP-binding cassette sub-family G member 4 (Abcg4) transport and was validated using quantitative RT-PCR. The validated gene was also induced by treatment of purified Retnla protein in RAW 264.7 cells incubated with acetylated low-density lipoprotein and Hepa1c1c7 cells. Taken together, these results indicates that Retnla might also accelerate initial step of RCT pathway, suggesting therapeutic value of Retnla in the treatment of hypercholesterolemia and atherosclerosis.

• Archives of Pharmacal Research
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• v.13 no.3
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• pp.227-232
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• 1990

A Physiologically based pharmacokinetic model was used to describe the distribition and elimination of cefriazone in the rat. To validate the practical application of the model, the effect of cffeine on the model was also examined. The model consisted of eleven compartments representing the major sites for ceftriaxone distribution including carcass which served as a residual compartment. Elimination was represented by renal and hepatic (metabolic biliary )excretion with GI secretion and re-absorption. The drug concentrations in most of the tissues were simulated using flow limited equations while brain levels were simulated using membrane limited passive diffusion distribution. The experimental data were obtained by averaging the concentration of drug in the plasma and tissues of five rats after i. v. injection of cefriazone 100 mg/kg without and with caffeine 20 mg/kg. The data for the amount of ceftriazone excreted in urine and gut contents were used to apportion total body clearance. HPLC with UV detection was used for the assay with 0.1-0.2 $\mu$g/ml sensitivity. The great majority of drug concentrations with and without caffeine show reasonably good agreements to the simulation results within 20%. The effect of caffeine on renal and hepatic clearances was apparent with 18.8% and 18.6% increase in the model values, respectively.

• Journal of the Korean Chemical Society
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• v.42 no.3
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• pp.266-276
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• 1998

Cholesterol supersaturation in bile, which causes gallstone formation, is the result of low bile acid secretion or high cholesterol secretion. The quantitative analysis of cholesterol, bile acids and sterols which are precursors of cholesterol have been used to examine the changes in bile component. We described a simple, sensitive and reproducible method for simultaneous determination of cholesterol, five bile acids and seven sterols in human bile juices and gallstones by capillary column gas chromatography-mass spectrometry (GC/MS). Clinical samples were hydrolyzed by alcoholic KOH, extracted twice (pH 14 and 1) and derivatized to trimethylsilyl (TMS) ether with $MSTFA/NH_4I$ (N-methyl-N-trimethylsilyltrifluoroacetamide/ammonium iodide) mixture in order to be detected on the GC/MS. The good quality control data were obtained through within-a-day and day-to-day test (RSD values were 1.72-13.79, 0.68-14.10, respectively) and the recovery range of them was 73.56-96. 95 Using this method, biliary and gallstone compositions in the patients with intrahepatic stones were analyzed. The amounts and its relative distribution of cholesterol, bile acids and sterols showed different pattern in bile juices and gallstones.

• Biomolecules & Therapeutics
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• v.23 no.4
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• pp.350-356
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• 2015

Functional dyspepsia (FD) is a prevalent idiopathic upper gastrointestinal (GI) disorder characterized by diverse symptomatology including epigastric pain or discomfort, postprandial fullness, and early satiety. Although its pathophysiological mechanisms have not yet been fully established, the available studies suggest that the etiology of FD is invariably multifactorial. Benachio-F$^{(R)}$ (BF) is a proprietary liquid formulation of 7 herbal extracts that has been proposed to address this multifactorial etiology using multi-drug phytotherapy. The pharmacological effects of BF, in comparison with those of two other herbal products (Whalmyungsu$^{(R)}$; WM and Iberogast$^{(R)}$; IB) were evaluated in rats. In a laparotomy-induced rat model of delayed GI transit, BF significantly accelerated the delayed gastric emptying caused by morphine, apomorphine, and cisplatin, and also significantly increased mean gastric transit, as compared to the control animals. BF markedly increased gastric accommodation in rats and produced higher gastric volume values than did the control treatment. The effects of BF were generally comparable or superior to those of WM and IB in these models. Furthermore, BF significantly stimulated biliary flow, as compared to the control treatment. These results indicated that BF might have great potential as an effective phytotherapeutic agent capable of reducing GI symptoms and increasing quality of life in FD patients.

• Journal of Life Science
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• v.21 no.12
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• pp.1772-1777
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• 2011

Cystic fibrosis transmembrane conductance regulator (CFTR) gene and sodium-independent $Cl^-/HCO_3^-$ anion exchanger (AE) genes are expressed in a wide variety of mammalian tissues including cholangiocytes. They play an important role in the regulation of intracellular pH (pHi) as well as in transepithelial acid/base transport necessary for biliary bicarbonate secretion. The aim of this study was to examine the expression level of CFTR gene and AE genes (AE1, AE2 and AE3) in the cholangiocytes and the hepatocytes, and also measure AE2 gene expression level after bile duct ligation (BDL). As we previously described, isolated hepatocytes and cholangiocytes from the liver of normal and BDL rats were prepared and gene expression levels were measured by using RT-PCR. We found that AE1, AE2, and AE3 genes were expressed in both hepatocytes and cholangiocytes, but CFTR was only in cholangiocytes. AE2 gene expression level was higher in the BDL hepatocytes than normal hepatocytes, which was significantly different between two groups. AE2 gene expression level was lower in the BDL cholangiocytes than normal cholangiocytes. However, AE2 gene expression level in both hepatocytes and cholangiocytes were not changed with a longer duration of BDL. These results suggest that CFTR and AE2 may play an important role in the pathogenetic mechanism of biliary cholestatic liver disease.

• The Korean Journal of Pharmacology
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• v.11 no.1 s.17
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• pp.47-53
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• 1975

The metabolism of many drugs and also of steroid hormones is mediated by enzymes located in the microsomal fraction in smooth surfaced endoplasmic reticulum of mammalian liver. The duration and intensity of action of many drugs are largely determined by the speed at which they are metabolized in the body. Repeated administration of phenobarbital results in the induction of enzymes that metabolize a number of drugs. Lee et al. reported that daily administration of phenobarbital in rats significantly increased the activities of amylase in the pancreatobiliary juice, but the concentration of cholate in the bile was significantly lower in the treated group than that in the control group. After animals were treated with $CCl_4$, histological changes were shown in the endoplasmic reticulum, decreased microsomal enzyme activity and decreased hepatic protein synthesis were apparent. The purpose of the present report was to study the interaction between a 'microsomal-stimulating' agent such as phenobarbital and a 'microsomal- depressing' agent such as $CCl_4$ on hepatic and pancreatic functions in rats. The results obtained are summarized as follows: 1. The mortality rate of $CCl_4$ treated group was 34% and was decreased this figure to 15% with phenobarbital pretreatment. 2. In animals treated with phenobarbital the volume of biliary-pancreatic secretion was markedly elevated but the volume was decreased significantly in animals treated with $CCl_4$. 3. Total bilirubin output was elevated markedly in the $CCl_4$ treated group of rats pretreated with phenobarbital. The bilirubin concentration was increased in $CCl_4$ treated group and decreased in the group treated phenobarbital alone. 4. The concentration and total output of cholate in the bile were significantly lower in the all experimental group than control group. 5. In the animals treated with phenobarbital alone and phenobarbital plus $CCl_4$, the activity of lipase in pancreatobiliary juice was elevated, while in the animals treated with $CCl_4$ alone no change was observed. 6. The activity of amylase in the pancreatobiliary juice was decreased in the $CCl_4$ treated group, but elevated markedly in phenobarbital group and also elevated in phenobarbital-$CCl_4$ group. By the above results, it is concluded, when the liver was damaged by $CCl_4$, the exocrine function of pancreas and liver was decreased simultaneously. However, in the animals pretreated with phenobarbital, the toxicity of $CCl_4$ on the liver and pancreas was reduced.

• The Korean Journal of Pharmacology
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• v.14 no.1_2
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• pp.47-54
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• 1978

Recently, a major resection of the pancreas has been carried out not only to treat carcinoma of pancreas but also chronic pancreatitis. But limited and often contradictory reports have been made on the exocrine effects after partial surgical pancreatectomy in mammals. It was suggested that the growth of the residual tissue in pancreatectomized rat is very active, because pancreas has the great power of regeneration after partial pancreatectomy, while others observed that rat pancreas after partial surgical resection revealed a perplexing mixture of atrophy and regeneration of acinar tissue. On the other hand, another results showed that the amount of insulin required to control diabetes after partial resection of pancreas is much greater than that needed after total pancreatectomy. Because the anti-insulin system, such as glucagon secretion and hypophyseoadrenal function, is probably depressed after total pancreatectomy. Furthermore, minimal resection line which will not influence the normal function of pancreas is not agreeable, such 75%, 80% or 95% resection of the total pancreas in rat. So far, studies on the exocrine function other than endocrine function after partial pancreatectomy have been limited. Therefore, the main purpose of this study is to examine the changes of exocrine as well as endocrine function of pancreas at the different time interval after 60% or 80% pancreatectomy in rats. The results summerized as follow: 1) In both 60% and 80% resected groups, a slight decrease of the total body weight was observed at a day after partial pancreatectomy in rats, but the body weight was continued to increase for following 100 days. 2) The weight of residual pancreas was continuously increased during experiment in both 60% and 80% resected groups. But the content of tissue protein in residual pancreas was significantly decreased comparing with those of resected pancreas. 3) The flow rate of pancreatico-biliary juice was significantly decreased immediately after pancreatectomy in both resected groups. But it was recovered to control level after a day in 60% resected group, after 30 days in 80% resected group. 4) The output of amylase and lipase in resected groups were significantly decreased right after pancreatectomy comparing with control group. In the 60% resected group, the output of amylase was recovered during the following 100 days after pancreatectomy, while lipase output in 3 days. However, in the 80% resected group, the output of amylase and lipase were not recovered during 100 days after pancreatectomy. 5) In order to examine the endocrine function, blood sugar level were examined at all experimental periods after partial pancreatectomy. There was no difference between control and 60% resected group in the sugar level. But in the 80% resected group the level was significantly incresed immediately after pancreatectomy, and reached the highest level at 3 days. Then it was decreased to control level during the next 10 days after pancreatectomy. The above results showed that in 60% resected group little changes were observed on pancreatic function, but severe functional impairments were observed in 80% resected group. This results suggested that the endocrine function was recovered within a short period, although the exocrine function was not recovered for a long time after 80% pancreatectomy in rats.

• Applied Microscopy
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• v.23 no.2
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• pp.53-77
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• 1993

In this study, an attempt was made to investigate the probable organelles participating in the secretion of biligrafin. The animals (ICR male mice, 25-30gm) were divided into normal control and 6 biligrafin injected groups to which 30% biligrafin (0.006ml/gm b.w.) were injected at 10, 20, 40, 80, 160 and 320 min prior to the sampling. The mice of each group were perfused through the heart with ice-cold 2.5% glutaraldehyde buffered with 0.1M Na-cacodylate (pH. 7.4) under the Na-pentobarbital (Nembtal 0.0015mg/gm b.w.) anesthesia and liver tissues were taken from each group. Some specimens were immersed 1 hr in the same solution used in the perfusion. After an overnight rinse in 0.1M Na-cacodylate buffer containing 10% DMSO and 7.6% sucrose, $75{\mu}m$ fronzen sections were made for cytochemical study. The sections were incubated in thiamin pyrophosphatase (TPPase) and inosine diphosphatase (ID Pase) media for 70 min at $37^{\circ}C$ respectively and acid phosphatase (AcPase) medium for 40 min at $37^{\circ}C$. They were postfixed in 1 % $OsO_4$ for 1 hr. The other specimens were immersed for 8 hrs in the fixative consisting of 2.5% glutaraldehyde and 3.0% paraformaldehyde buffered with Na-cacodylate (pH. 7.4). All of the osmificated specimens were processed for electron microscopy. In both normal and biligrafin injected groups, endoplasmic reticulum (ER), vacuoles, Golgi apparatus and lysosomes were seen in the vicinity of bile canaliculus. In the biligrafin injected groups, however, the Golgi apparatus appeared to be decreased and ER and vacuoles were dilated and increased. The rough endoplasmic reticulum (RER) having a few attached ribosomes appeared to be the round saccule, especially at 20 min after biligrafin injection. Smooth endoplasmic reticulum (SER) seemed to be formed by the detachment of ribosomes at the cisternal end of RER. The cistern of SER showed saccules which probably budded off to form the vacuole. The vacuoles were devoid of visible centents. This finding seemed to be in agreement with the biochemical property of the bile constituents. The fusion between the vacuoles and bile canaliculus were frequently seen in the groups injected with biligrafin. The lysosome did not show any changes in the biligrafin injected groups. Accumulation of some material and lipid droplets were seen at the 40 and 80 min after biligrafin injection, especially at the latter. At 160 and 320 min after biligrafin injections, however, they were decreased successively while the RER stack, free ribosomes and polysomes were increased. Although the reactive products of TPPase and IDPase were observed in the ER saccules and vesicles of the normal control and biligrafin injected groups, the fusion between the bile canaliculus and saccules or vesicles could easily be seen in the latter. The AcPase activity, however, was observed in the cistern at the maturing face of Golgi apparatus and lysosomes in both normal and biligrafin groups. The results suggest that the biligrafin is excreted via the vesicles, vacuoles or sacoules probably derived from the SER without the participation of Golgi apparatus and lysosomes, and the excess amount of material is stored as inclusions during the repairing of the organelles being overactive.