• 생약학회지
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• 제19권4호
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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.

• 대한수의학회지
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• 제35권3호
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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.

• 한국컴퓨터정보학회논문지
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• 제21권12호
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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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• 제13권3호
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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.

• 대한화학회지
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• 제42권3호
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• pp.266-276
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• 1998

담즙산 분비 저하 및 콜레스테롤의 과도한 분비는 담석 형성의 주된 원인으로 담즙내의 담즙산과 콜레스테롤 및 그 전구 물질인 스테롤의 상대적인 농도는 담즙 성분의 이상을 알아보기 위한 중요한 지표로 알려져 있다. 이에 본 연구에서는 염기를 이용한 가수 분해와 pH 14와 1에서 두 번의 액체-액체 추출을 거친 후, $MSTFA/NH_4I$ 혼합액으로 유도체화 시키는 전처리 방법과 GC/MS를 이용한 새로운 분석 방법을 설정, 담즙산과 스테롤 그리고 콜레스테롤의 동시 분석을 시도하였다. 그 결고 회수율은 73.56-96.95% 이었고 within-a-day 및 day-to-day 분석의 RSD 값은 각각 1.72-13.79%, 0.68-14.10% 이었으며, 이 방법을 간내 담석증 환자에 적용하여 담즙과 담석내에 존재하는 7종의 스테롤과 5종의 담즙산, 그리고 콜레스테롤의 농도 및 그들간의 상대적인 농도 분포를 측정한 결과 담즙고 담석에서 현저히 다른 차이를 보였다.

• Biomolecules & Therapeutics
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• 제23권4호
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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.

• 생명과학회지
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• 제21권12호
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• pp.1772-1777
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• 2011

본 연구는 흰쥐의 담관 세포와 간세포에서 CFTR과 $AE1{\cdot}AE2{\cdot}AE3$ 유전자들의 발현 유무를 조사하고 흰쥐에서 담관 결찰 후 AE2 유전자의 발현의 변화를 관찰하고자 하였다. 200-250 g의 Sprague Dawley 계 흰쥐 24마리의 총담관을 결찰한 후 4 주 동안 1 주일에 6마리씩 희생하여 간세포와 담관 세포를 분리하였다. 6마리는 대조군으로 사용하여 간세포와 담관 세포에서 CFTR 유전자와 $AE1{\cdot}AE2$와 AE3 유전자 발현을 조사하고 담관 결찰 후 1 2 3 4주 간격으로 AE2 유전자 발현을 조사하였다. $AE1{\cdot}AE2$ 와 AE3는 간세포와 담관 세포에서 발현되었고 CFTR은 담관 세포에서만 발현되었다. 담관 결찰 담관세포군에서 AE2 유전자의 발현은 대조군인 정상 담관세포군에 비해서 낮았다. 결찰 담관세포군에서 AE2 유전자의 발현은 결찰 기간에 따라 차이가 없었다. 담관 결찰 간세포군에서 AE2 유전자의 발현은 대조군인 정상 간세포군에 비해서 경계적 유의성을 보이며 증가하는 경향이 있었다. 결찰 간세포군에서 AE2 유전자의 발현은 결찰 기간에 따라 차이는 없었다. 따라서 $CFTR{\cdot}AE1{\cdot}AE2$ 그리고AE3 는 간세포와 담관 세포에서 중탄산염이온과 수액을 매개하는 주된 이온 전달체라는 사실을 고려할 때 담도 담즙정체 간질환에서CFTR과 AE2 발현의 변화는 병리학적 기전에 중요한 역할을 할 수 있으리라고 생각된다.

• 대한약리학회지
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• 제11권1호
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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.

• 대한약리학회지
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• 제14권1_2호
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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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• 제23권2호
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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.