• Journal of Pharmaceutical Investigation
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• v.7 no.1_4
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• pp.38-50
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• 1977

A study on the mechanism of biliary and urinary excretion of chloramphenicol has been performed in the dog. 1) Chloramphenicol administered intravenously to dogs with ligated renal pedicle, readily appeared in bile greater than in plasma. 6.9% of a 50mg /kg i. v. dose of chloramphenicol were excreted into bile within 100 minutes. During the same periods of above experiment, the bile/plasma concentration ratios(B/P ratios) were 46 to 87. 2) Chloramphenicol injected into the vein of dog was rapidly excreted into urine. 18% of the administered dose were excreted into urine within 70 minutes. In the same periods of this experiment, Ccm/Ccr ratios were greater than 1.0 in most cases. 3) In experiment of simultaneous measurement of biliary and urinary excretion of chloramphenicol, Ccm/Ccr ratios were less than 1.0 and B/P ratios were 50 to 52. 4) In experiment measured simultaneously biliary and urinary excretion both Ccm/Ccr and $C^Hcm$(hepatic clearance) were significantly declined by probenecid, but not affected by 2,4-DNP and aminophylline although 2,4-DNP increased only bile flow and aminophylline both bile and urine volume. 5) Ccm/Ccr and $C^Hcm$ were increased in proportion to increment of plasma concentration ranging from 3.3 to 30 mg% of chloramphenicol. But when plasma concentration were increased to 70mg %, Ccm/Ccr were not increased and $C_Hcm$ were reduced about 30% in comparison with values obtajned at 30mg% of chloramphenicol. 6) Free/Bound(free to bouid from) ratios ranging from 1.0 to 90.0mg% of chloramphenicol were 76.2+3.72% $(mean{\pm}S.E.)$ Above results suggest that chloramphenicol is excreted into bile by a process of active trasport, that excretion of chloramphenicol into urine was made up with dual process, reabsorption and secretion, and that renal secretion was attained by active trasport process although renal reabsorption process could not understand.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.74-74
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• 1997

Chicory is used popularly. We use leaves of the plant as ordinary mea1, and roots as a substitute of tea materials. It also has been asserted that it has clinical effects on weakness, hepatic disease, diabetes, etc. However, experimental evidences are so insufficient that we started these studies. For antiinflammatory activity, MeOH Ex. was orally administered to rats, and decreased amounts of paw edema induced by carrageenan injection were measured. For bile secretion increament, rats were administered total MeOH, EtOAc fraction, and BuOH fraction Ex. respectively. One hour later, bile ducts were cannulated, and we collected bile every 20 minutes for 4 hours. For hepatoprotective activity, CCl$_4$-intoxicated mouse were treated with MeOH Ex., then s-GPT, S-GOT, and liver weight were measured. For antidiabetic activity, rats were induced diabetes by streptozocin 45mg/kg(i.v) injection. One week later, 1000mg/kg of total MeOH Ex. of chicory root was orally administered. We divided rats into three groups. Group 1 rats were administered only once, group 2 ones once a day for one week, and group 3 ones for three weeks. The concentrations of serum glucose were measured before and after administration. For antihypertensive activity, SHR were administrated total MeOH Ex. of chicory once a day for 8 days, and were measured blood pressure on 1st, 3rd, 6th and 8th day. Total MeOH, EtOAc fraction, and BuOH fraction Ex. increased bile secretion in rats, and decreased liver toxicity induced by CCl$_4$ in mouse. Total MeOH, Ex. of chicory roots has antiinflammatory effect, and decreased blood glucose concentration in group 2 and 3 rats. It was revealed not lowering blood pressure significantly in SHR.

• Parasites, Hosts and Diseases
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• v.57 no.4
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• pp.379-387
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• 2019

Clonorchis sinensis is a carcinogenic human liver fluke that promotes hepatic inflammatory environments via direct contact or through their excretory-secretory products (ESPs), subsequently leading to cholangitis, periductal fibrosis, liver cirrhosis, and even cholangiocarcinoma (CCA). This study was conducted to examine the host inflammatory responses to C. sinensis ESPs and their putative protein components selected from C. sinensis expressed sequenced tag (EST) pool databases, including $TGF-{\beta}$ receptor interacting protein 1(CsTRIP1), legumain (CsLeg), and growth factor binding protein 2 (CsGrb2). Treatment of CCA cells (HuCCT1) with the ESPs or bacterial recombinant C. sinensis proteins differentially promoted the secretion of proinflammatory cytokines ($IL-1{\beta}$, IL-6, and $TNF-{\alpha}$) as well as anti-inflammatory cytokines (IL-10, $TGF-{\beta}1$, and $TGF-{\beta}2$) in a time-dependent manner. In particular, recombinant C. sinensis protein treatment resulted in increase (at maximum) of ~7-fold in $TGF-{\beta}1$, ~30-fold in $TGF-{\beta}2$, and ~3-fold in $TNF-{\alpha}$ compared with the increase produced by ESPs, indicating that CsTrip1, CsLeg, and CsGrb2 function as strong inducers for secretion of these cytokines in host cells. These results suggest that C. sinensis ESPs contribute to the immunopathological response in host cells, leading to clonorchiasis-associated hepatobiliary abnormalities of greater severity.

• Journal of Ginseng Research
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• v.46 no.4
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• pp.561-571
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• 2022

Background: Ginsenoside Rb1 (GRb1) is capable of regulating lipid and glucose metabolism through its action on adipocytes. However, the beneficial role of GRb1-induced up-regulation of adiponectin in liver steatosis remains unelucidated. Thus, we tested whether GRb1 ameliorates liver steatosis and insulin resistance by promoting the expression of adiponectin. Methods: 3T3-L1 adipocytes and hepatocytes were used to investigate GRb1's action on adiponectin expression and triglyceride (TG) accumulation. Wild type (WT) mice and adiponectin knockout (KO) mice fed high fat diet were treated with GRb1 for 2 weeks. Hepatic fat accumulation and function as well as insulin sensitivity was measured. The activation of AMPK was also detected in the liver and hepatocytes. Results: GRb1 reversed the reduction of adiponectin secretion in adipocytes. The conditioned medium (CM) from adipocytes treated with GRb1 reduced TG accumulation in hepatocytes, which was partly attenuated by the adiponectin antibody. In the KO mice, the GRb1-induced significant decrease of TG content, ALT and AST was blocked by the deletion of adiponectin. The elevations of GRb1-induced insulin sensitivity indicated by OGTT, ITT and HOMA-IR were also weakened in the KO mice. The CM treatment significantly enhanced the phosphorylation of AMPK in hepatocytes, but not GRb1 treatment. Likewise, the phosphorylation of AMPK in liver of the WT mice was increased by GRb1, but not in the KO mice. Conclusions: The up-regulation of adiponectin by GRb1 contributes to the amelioration of liver steatosis and insulin resistance, which further elucidates a new mechanism underlying the beneficial effects of GRb1 on obesity.

• 한국생물공학회:학술대회논문집
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• 2003.10a
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• pp.305-306
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• 2003

To treat fulminant hepatic failure (FHF) patients, various extracorporeal bioartificial liver (BAL) systems have been developed. Several requirements should be met for the development of BAL systems: hepatocytes should be cultured in a sufficiently high density; their metabolic functions should be of a sufficiently high level and duration; and the BAL systems module should permit scaling-up and aseptic handling. Several investigators have found that freshly isolated primary hepatocytes can be cultured into three dimensional, tightly packed, freely suspended, multicellular aggregates, or spheroids. These specialized cell structures exhibited enhanced liver specific functions and a prolonged differentiated state compared to cells maintained in a monolayer culture. Cells in spheroids appear to mimic the morphology and ultrastructure of the in vivo liver lobule. The ability of hepatocytes to organize into three-dimensional structures was hypothesized to contribute to their enhanced liver-specific activities. In this study, the ammonia removal rate and urea secretion rate of pig hepatocytes spheroids encapsulated in Ca-alginate bead were determined. A packed-bed bioreactor with encapsulated pig hepatocytes was devised as BAL support system. The efficacy of the system was evaluated in vitro.

• Journal of Biomedical Engineering Research
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• v.19 no.3
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• pp.215-224
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• 1998

This paper is fundamental study to develope the extracorporeal liver support system for patient with fulminant hepatic failure(FHF) or being expected for orthotopic liver transplantation. The polyurethane foam, which is composed of the density of 33kg/m3, the average pore diameter of 500${\mu}{\textrm}{m}$, the closed window of 60-70%, was manufactured with the prepolymer of 15% NCO-, Hepatocytes were inoculated to form spheroids in polyurethane foam. The time of spheroid formation in BSA(Bovine Serum Albumin) coated polyurethane foam was shorter than that in raw polyurethane foam. To verify the function of hepatocyte spheroids, we measured ammonia removal rate, urea and albumin secretion rate. Polyurethane foam was suitable for culture of hepatocyte spheroids. And culture of hepatocyte spheroids in polyurethane foam has high possibility in using as an extracorporeal liver support system.

• International Journal of Oral Biology
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• v.31 no.4
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• pp.119-125
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• 2006

The importance of phytoestrogens to human health is currently being actively investigated. Hesperidin, abundantly found in citrus fruits, is known to possess antioxidant, anticancer, and anti-inflammatory effects. Recently, it has been reported that hesperidin inhibits bone loss and decreases serum and hepatic lipids in ovariectomized mice. In our study, to determine the possible role of hesperidin in the regulation of bone metabolism, we observed the effects of hesperidin on the proliferation and activity of osteoblasts, as well as the effects of hesperidin on osteoclast generation and activity. We observed that, when treated with hesperidin, the number and viability of osteoblastic cells increased, alkaline phosphatase (ALP) activity of osteoblastic cells increased, and osteoprotegerin (OPG) secretion from MG63 cells decreased. Hesperidin treatment had no effect on the osteoclast generation and activity in the bone marrow cell culture, but decreased the number and resorptive activity of osteoclasts generated from RAW/264.7 cells. Taken together, these results indicate that hesperidin increases the proliferation and activity of osteoblasts, while inhibiting generation and activity of osteoclasts. Although the precise role of hesperidin remains to be elucidated, our study suggests that it is one of the important modulators of bone metabolism.

• Journal of Pharmacopuncture
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• v.23 no.2
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• pp.79-87
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• 2020

Objectives: Ginsenosides found in ginseng, and the hydrolysates derived from their conversion, exhibit diverse pharmacological characteristics [1]. These have been shown to include anti-cancer, anti-angiogenic, and anti-metastatic effects, as well as being able to provide hepatic and neuroprotective effects, immunomodulation, vasodilation, promotion of insulin secretion, and antioxidant activity. Therefore, the purpose of this study was to examine how quickly the ginsenosides decompose and what kinds of degradation products are created under physicochemical processing conditions that don't involve toxic chemicals or other treatments that may be harmful. Methods: The formation of ginsenoside-Rg2 and ginsenoside-Rg3 was examined. These demonstrated diverse pharmacological effects. Results: We also investigated physicochemical factors affecting their conversion. The heating temperatures and times yielding the highest concentration of ginsenosides (-Rb1, -Rb2, -Rc, -Rd, -Rf, -Rg1, and -Re) were examined. Additionally, the heating temperatures and rates of conversion of these ginsenosides into new 'ginseng saponins', were examined. Conclusion: In conclusion, obtained provide us with effective technology to control the concentration of both ginsenosides and the downstream converted saponins (ginsenoside-Rg2, Rg3, Rg5, and Rk1 etc.), as well as identifying the processing conditions which enable an enrichment in concentration of these compounds.

• Biomolecules & Therapeutics
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• v.2 no.2
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• pp.173-184
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• 1994

The general and some pharmacological actions of DWP 305 were investigated in animals and the following results were obtained. In central nervous system, DWP 305 had no effects on the pentobarbital induced anaesthesia, locomotor activity, rotarod test, traction test, analgesic action in mice and body temperature in rat. DWP 305 showed no depressive action on convulsion induced by strychnine, electronic shock and pentylenetetrazole. From these results, DWP 305 was considered to have no pharmacological effect on the central nervous system. Furthermore, DWP 305 had no influences on the normal blood pressure and heart rate. In the isolated ileum of guinea pig, DWP 305 inhibited contractive effects against the acetylcholine (10$^{-6}$ g/mι), histamine (10$^{-6}$ g/mι), 5-hydroxytryptamine (10$^{-6}$ g/mι) and BaCl$_2$(10$^{-4}$ g/mι) at a concentration of 2.15$\times$10$^{-4}$ g/ml in bath. In the isolated trachea and vats deference, DWP 305 showed no effect on the contractions produced by histamine and norepinephrine, respectively. DWP 305 showed inhibitory effect on the contractions produced by acetylcholine and oxytocin at a concentration of 2.15$\times$10$^{-4}$ g/ml on the isolated nonpregnant rat uterus. DWP 305 had no effect on the isolated right atrium of guinea pig, bile excretion, urine volume, pH, gastrointestinal motility, gastric secretion and blood aggregation.

• YAKHAK HOEJI
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• v.30 no.5
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• pp.253-265
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• 1986

Among 230 species of herbal drugs screened, thirty one show the anthelmintic activities in vitro against Clonorchis sinensis, the chinese liver fluke. The active substances have been isolated and their structures identified. Some of the active substances and their derivatives have been synthesized, followed by anthelmintic activity tests. The extracts from the active drugs cause damages in organs of the adult worm in the hepatic duct of rabbit. Some fresh water fish, which function as bad hosts for the fluke, excrete defense substances against the cercaria of the fluke. The defense substances have been isolated from Cyprinus carpio and Cyprinus carpio nudus, followed by structural identification. The results are summarized as follows: l) The bark of Machilus thunbergii as well as the seed of Schizandra chinensis contain meso-dihydro-guaiaretic acid as the anthelmintic component. Among derivatives synthesized, 4-phenyl-1-((3, 4-dihydroxyphenyl)-, 4-phenyl-1-(3-hydroxy-4-methoxy phenyl)-and 4-phenyl-1-(4-hydroxy-3-methoxy phenyl)-2, 3-dimethyl butanes show considerable activities. Administration of the bark extract mainly damages the bladder of the adult worm. 2) The active substance from the roasted fruit of Prunus mume is 2-hydroxymethylfurfural. This substance is produced during the roasting process. Administration of the fruitextract causes a damage of the bladder of the adult worm. 3) The active substance from the root of Scutellaria baicalensis is 5.2'-dihydroxy-6, 7, 8, 6'-tetramethoxyflavone. 4) Beside alantolactone, a very strong anthelmintic component is contained in the root of Inula helenium. Administration of the root extract causes irreversible damage on the worm, affecting mainly the reproductive organs. 5) The cercaricidal substances from the epidermis of C. carpio and C. carpio nudus are ethyl linoleate and linoleic acid, respertively. 6) The cercaricidal substances from various kinds of fresh water fish have different $R_f$ values, implying that the defense substances are species-specific. Unexpectedly, the fish with good host function, for example Pseudorasbora parva, excrete the defense substances, too. The defense substances are possibly organ-specific in individual species; the organs essenstial for the existence of the species excrete the defense substances, allowing other parts to be invaded by the cercaria. 7) The cercaricidal fraction of Carassius carassius is detected only in the fish which have been collected during the summer time from May to September, Its secretion is not dependent on water temperature. Thus, it seems to be possible that the secretion of the defense substance would be stimulated through a contact between the fish and cercaria.