• The Journal of Pediatrics of Korean Medicine
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• v.27 no.1
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• pp.69-81
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• 2013

Objectives In this study, effects of Macmundongtang (MMT) on ATP or TNF-${\alpha}$ or PMA or EGF induced MUC5AC mucin production and gene expression from human airway epithelial cells and the increase in airway epithelial mucosubstances of rats were investigated. Materials and Methods Confluent NCI-H292 cells were pretreated for 30min in the presence of MMT and treated with ATP ($200{\mu}M$) or PMA (10 ng/ml) or EGF (25 ng/ml) or TNF-${\alpha}$ (0.2 nM) for 24hrs, to assess the effect of MMT both on ATP- or PMA- or 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). At the same time, hypersecretion of airway mucus was induced by exposure of rats to SO2 during 3 weeks. Effect of orally-administered MMT during 2 weeks on increase in airway epithelial mucosubstances from tracheal goblet cells of rats was assesed using histopathological analysis after staining the epithelial tissue with PAS-alcian blue. Possible cytotoxicity of MMT was assessed by investigating the potential damage of kidney and liver functions by measuring serum GOT/GPT activities and serum BUN concentration of rats and the body weight gain during experiment, after administering MMT orally. Results (1) MMT did not only inhibit but also increased MUC5AC mucin productions and expression levels of MUC5AC gene from NCI-H292 cells. (2) MMT did not decrease the amount of intraepithelial mucosubstances of trachea of rats. (3) MMT did not show renal and hepatic toxicities and did not affect body weight gain of rats during experiment. Conclusions The result from the present study suggests that MMT might normalize the production and gene expression of airway mucin observed in various respiratory diseases accompanied by yin-deficiency, without in vivo toxicity to liver and kidney functions after oral administration.

• Korean Journal of Pharmacognosy
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• v.26 no.4
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• pp.390-410
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• 1995

This study was attempted to investigate the effects of Composite Preparation (Samulchungkan-Tang) extract (SCTE), Scutellarias Radix extract (SRE), Artemisiae iwayomogii Herba extract (AIHE), Artemisia capillaris Flos extract (ACFE), Paeaniae Radix extract (PRE) and Gardeniae Fructus extract (GFE) on the activities of GOT, GPT, ALP and LDH, and Content of total cholesterol in serum of $CCl_4$ and ${_D}-galactosamime$ intoxicated rats, and bile flow in rats. 1) In $CCl_4-intoxicated$ rats-The activities of S-GOT and S-GPT which were elevated by $CCl_4$ were significantly decreased in dose of SCTE 450 mg/kg, ACFE 600 mg/kg and GFE 300 mg/kg, respectively as compared to $CCl_4$ intoxicated rats. ALP activity increased by $CC1_4-treatment$ was markedly decreased in dose of SCTE 450 mg and 600 mg/kg, SRE 400 mg/kg, AIHE 400 mg/kg, ACFE 600 mg/kg and PRE 300 mg/kg, and LDH activity in SCTE 450 mg and 600 mg/kg, ACFE 600 mg/kg and GFE 300 mg/kg, respectively compared to $CCl_4$ treated rates. ACFE 400 mg/kg and PRE 300 mg/kg decreased the content of total cholesterol increased by $CCl_4$, the liver weight in all sample administered groups was decreased significantly as compared to $CCl_4$ treated groups. 2) In ${_D}-galactosamine$ intoxicated rats-Sample of SCTE 450 mg and 600 mg/kg, SRE 400 mg/kg, AIHF 400 mg and 600 mg/kg, ACFE 600 mg/kg, PRE 300 mg/kg and GFE 300 mg and 500 mg/kg decreased the activities of S-GPT, ALP and LDH which was increased by ${_D}-galactosamine$ intoxication, compared to ${_D}-galactosamine$ intoxicated groups. In S-GOT activity elevated by ${_D}-galactosamine$ was significantly decreased by SCTE 450 mg/kg, ACFE 600mg/kg, AIHE 600 mg/kg, PRE 300 mg/kg, GFE 300 mg and 500 mg/kg. However, SCTE 600 mg/kg, SRE 400 mg/kg, and AIHE 400 mg/kg were not effected significantly. 3) In bile secretion-SCTE 450 mg and 600 mg/kg, ACFE 600 mg/kg and GFE 500mg/kg increased significantly the amount of bile secretion as compared to normal groups, but AIHE 400 mg/kg, SRE 400 mg/kg, and PRE 300 mg/kg did not effected significantiy.

• The Journal of Pediatrics of Korean Medicine
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• v.30 no.2
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• pp.31-46
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• 2016

Objectives In this study, the effects of Ja-eum-gang-hwa-tang (JGT) on the increase in airway epithelial mucosubstances of rats and ATP- or PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production and gene expression from human airway epithelial cells were investigated. Materials and Methods Hypersecretion of airway mucus was produced by exposure of $SO_2$ to rats for 3 weeks. The effect of orally-administered JGT for 2 weeks on increased epithelial mucosubstances from tracheal goblet cells of rats was assessed by using histopathological analysis after staining the epithelial tissue with Hematoxylin-eosin and PAS-alcian blue. Possible cytotoxicity of JGT was assessed by investigating the potential damage on kidneys and liver functions by measuring serum GOT/GPT activities and serum BUN concentration of rats and the body weight gain during experiment. Also, the effect of JGT on ATP- or PMA- or 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 JGT and treated with ATP ($200{\mu}M$) or PMA ($10ng/ml$) or EGF ($25ng/ml$) or TNF-${\alpha}$ (0.2 nM) for 24 hrs to assess the effect of JGT both on ATP- or PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production by using enzyme-linked immunosorbent assay (ELISA) and on gene expression by the same inducers using reverse transcription-polymerase chain reaction (RT-PCR). Results (1) JGT decreased the amount of intraepithelial mucosubstances of trachea of rats. (2) JGT did not show any renal and hepatic toxicities, and did not affect body weights either. (3) JGT significantly inhibited ATP-, PMA-, EGF-, and TNF-${\alpha}$-induced MUC5AC mucin productions from NCI-H292 cells. (4) JGT inhibited EGF-, and PMA-induced expression levels of MUC5AC gene in NCI-H292 cells. However, ATP- and TNF-${\alpha}$-induced MUC5AC gene expression levels were not affected in NCI-H292 cells. Conclusions The result from the present study suggests that JGT might control the production and gene expression of airway mucin observed in various respiratory diseases which accompanied by mucus hypersecretion. Also, JGT did not show liver toxicity or impact on kidney functions. The effect of JGT should be further studied by using animal experimental models which can show proper pathophysiology of airway diseases.

• Journal of the Korean Applied Science and Technology
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• v.37 no.3
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• pp.398-408
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• 2020

The purpose of the present study was to investigate the mechanism of metabolic partitioning between oxidization and esterification of liver fatty acids synthesized and secreted by the liver from egg yolk-fed laboratory rats. Animals were divided into four groups and orally administered egg yolk daily for 30 days: CON (control group, 1.0 g of saline solution), T1 (1.0 g of pork belly oil), T2 (1.0 g of egg yolk), and T3 (1.0 g of pork belly oil and 1.0 g of egg yolk, alternatively each week). The accumulation rate of [¹⁴C]-labelled lipid in liver was lowest in T2 among all treatments (P<0.05). Phospholipid secretion was higher in T2 than other treatments (P<0.05). The triglycerol secretion was highest in T1 and higher in the order of CON, T3, and T2 (P<0.05). Metabolic partitioning rate of phospholipid from total glycerolipid was highest in T2, followed by T3, CON and T1 (P<0.05). The ¹⁴CO₂ production from total glycerolipid was the highest in T2 and showed a high oxidation rate compared to CON, T1, and T3 (P<0.05). Metabolic partitioning of glycerolipid from the liver decreased in triglycerol of T2 compared to CON, T1, and T3, whereas phospholipids of T2 increased (P<0.05).

• Polymer(Korea)
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• v.32 no.2
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• pp.131-137
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• 2008

We have fabricated polystyrene (PS) nanofibrous scaffold for hepatocyte culture by electrospinning method and subsequently coated with specific ligand of Poly[N-p-vinylbenzyl-O-$\beta$-D-galactopyranocyl-($1{\rightarrow}4$)-D-gluconamide](PVLA) to enhance hepatocytes attachment. Rat hepatocytes behavior on the PVLA-coated and non-coated PS nanofibrous matrices have been investigated. Electrospun PS nanofiber structures revealed randomly aligned fibers with average diameter of 500 nm. It is observed that PS nanofibrous matrix could incorporate many cells into the interior of the matrix probably due to the suitable pore size. Cell viabilities cultured on PVLA-coated PS nanofibrous mats were maintained for 3 weeks, while it was decreased rapidly on PVLA-coated PS dishes. High hepatic functions especially for albumin secretion and ammonia removal were maintained at least for 2 weeks on nanofibrous mats but rapidly decreased on flat PS dishes. These results indicate that nanofibrous structure enabled 3-D culture with high level of cell-cell contact results in providing cell-cell communications and subsequent long-term maintenance of specific cell functions.

• KSBB Journal
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• v.29 no.1
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• pp.58-66
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• 2014

Demand for in vitro pharmacological evaluation and toxicity test using human hepatocytes has been increasing. In USA and Europe, human hepatocytes obtained from donated whole liver unsuitable for transplantation were distributed to researchers and deposited in cell bank facility as cryopreserved vial. In Korea, however, incidence of transplantation- inappropriate whole liver has been quite low and the whole livers almost have so severe liver disease such as fatty or fibrotic liver that cannot meet the demand. In this study we aimed to isolate human hepatocytes from liver resection surgery-originated partial liver, and assure the isolated human hepatocytes and its cryopreserved hepatocytes to be qualified for the in vitro pharmacological evaluation and drug toxicity tests. We compared those with commercially available human hepatocyte, BD $GenTest^{TM}$ by cell morphology, hepatic gene expression, urea synthesis, albumin secretion, ammonia removal, and cytochrome P450 induction activities. Changes in hepatotoxic gene expression after cryopreservation are evaluated with a typical hepatotoxic drug, acetaminophen. Consequently, the fresh hepatocytes from the partial liver and its cryopreserved hepatocytes expressed their intrinsic hepatic functions well and showed equal hepatotoxicity gene expression trend regardless to cryopreservation. Therefore, liver resection surgery-originated partial liver can be used as a useful source of human hepatocytes for various pharmacological and hepatotoxicity test.

• 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.

• Journal of Food Hygiene and Safety
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• v.29 no.2
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• pp.85-91
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• 2014

Deoxynivalenol (DON) and related trichothecene mycotoxins are extensively distributed in the cereal-based food and feed stuffs worldwide. Recent climate changes and global grain trade increased chance of exposure to more DON and related toxic metabolites in poorly managed production systems. Monitoring the biological and environmental exposures to the toxins are crucial in protecting human and animals from toxicities of the hazardous contaminants in food or feeds. Exposure biomarkers including urine DON itself are prone to shift to less harmful metabolites by intestinal microbiota and liver metabolic enzymes. De-epoxyfication of DON by gut microbes such as Eubacterium strain BBSH 797 and Eubacterium sp. DSM 11798 leads to more fecal secretion of DOM-1. By contrast, most of plant-derived DON-glucoside is also easily catabolized to free DON by gut microbes, which produces more burden to body. Phase 2 hepatic metabolism also contributes to the glucuronidation of DON, which can be useful urine biomarkers. However, chemical modification could be very typical depending on the anthropologic or genetic background, luminal bacteria, and hepatic metabolic enzyme susceptibility to the toxins in the diet. After toxin exposure, effect biomarkers are also important in estimating the linkage and mechanisms of foodborne diseases in human and animal population. Most prominent adverse effects are demonstrated in the DON-induced immunological and behavioral disorders. For instance, acutely elevated interleukin-8 from insulted gut exposed to dietaty DON is a dominant clinical biomarker in human and animals. Moreover, subchronic exposure to the toxins is associated with high levels of serum IgA, a biological mediator of IgA nephritis. In particular, anorexia monitoring using mouse models are recently developed to monitor the biological activities of DON-induced feed refusal. It is also mechanistically linked to alteration of serotoin and peptide YY, which are promising biomarkers of neurological disorders by the toxins. As animal-alternative biomonitoring, huamn enterocyte-based assay has been developed and more realistic gut mimetic models would be useful in monitoring the effect biomarkers in resposne to toxic contaminants in the future investigations.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.2
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• pp.153-166
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• 2013

Yang deficiency pattern is a representative syndrome differentiation. This article is a study on to which categories of modern diseases yang deficiency is assigned by reference to modern clinical papers and the meaning of yang deficiency interpreted with a perspective of Korean Medicine and a modern perspective. Yang deficiency, yang qi deficiency, lack of yang qi and yang qi debilitation are the words found in "Nei Ching" and yang qi can be interpreted as something to warm, drive and arouse. Zhangzhongjing considered recovery or loss of Yang as the key to life in "Shanghanlun". Danxi proposed "Yang being liable to hyperactivity, Yin being insufficient" and emphasized pathological ministerial fire of Yang exuberance rather than physiological ministerial fire of Yang deficiency. Zhangjingyue proposed "Yang not being in excess, Yin being often deficient" and understood growth and decline of yin qi are all led by yang qi and put emphasis on true yin in addition to yang qi. Diseases of yang deficiency pattern are related with decline of metabolic level, hypofunction of internal secretion, disorder of immune function, disorder of automatic nerve system, sympathetic nerve inhibition, metabolic disorder of microelements, increase of cGMP, change of microcirculation, low speed of blood stream, kidney malfunction. Diseases related with kidney are sterility, polycystic ovary syndrome, spinal stenosis, edema, renal failure, IgA nephropathy, erectile dysfunction, nephritis, prostatitis, benign prostatic hyperplasia, decrease of adrenal cortical hormone by nephrotic syndrome, myelodysplastic syndrome. Disease related with heart are heart failure, arrhythmia, cardiomyopathy, atherosclerosis heart disease, hypertension, hyperlipidemia, pulmonary heart disease. Diseases related with spleen are irritable bowel syndrome, ulcerative colitis. Diseases related with liver are hypothyroidism, liver cirrhosis ascites, hepatitis B, chronic hepatitis, hepatic diabetes. Diseases related with lung are allergic rhinitis, cough variant asthma, bronchial asthma, pulmonary emphysema. And diabetes mellitus, metabolic syndrome, aplastic anemia, headache, encephalatrophy, Alzheimer's disease are also related with yang deficiency.

• Journal of Nutrition and Health
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• v.27 no.10
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• pp.1048-1057
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• 1994

Nonobese NIDDM patients were studied were studied with respect to changes in visceral protein status, serum glucose and lipids and insulin secretion capacity before and after intake of enteral formula. Patients with renal or hepatic disease, gastrectomy, malabsorption, weight gain over past 6 months and poorly controlled blood glucose level were excluded. Eighteen patients served as case and administered, in addition of their usual diet, 400ml of enteral formula for 8 weeks. Another 18 patients participated in controls and had usual food intake for 8 weeks. In the begining, the levels of fasting and postprandial glucose, glycated hemoglobin, triglyceride, HDL, LDL, total cholesterol, albumin, total protein and transferrin and glucose response area on oral glucose tolerance test were not different between two groups. The response areas of insulin, C-peptide and free fatty acid and serum IGF-1 level were higher in the case than in the control group. Energy intake of patients given enteral formula exceeded their estimated energy requirements(108%) and they consumed a mean of 112g protein per day. Patients given enteral formula showed an increase in body weight(4.4%), serum transferrin(10%), IGF-1(13%) and triglyceride(34%) while controls showed no changes in those parameters at 8 weeks compared to initial values. There were no significant changes after 8 weeks in the levels of glucose, glycated hemoglobin, HDL, LDL, total cholesterol, total protein and albumin and response areas of glucose, insulin, C-peptide and free fatty acid in both groups compared to initial values. This study suggests that nutrition supplement with enteral formula can increase body weight and visceral protein status in nonobese NIDDM patients without changes in blood glucose. However, excessive calorie intake could temporarily increase serum triglyceride. In addition, this study indicates that serum transferrin and IGF-1 are more sensitive indicators to changes of protein intake than serum albumin and total protein.