• Archives of Pharmacal Research
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• v.28 no.4
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• pp.451-457
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• 2005

Experimental studies have demonstrated that the triple combination of amantadine (A)/ ursodeoxycholic acid (UDCA, U)/ biphenyl dimethyl dicarboxylate (DDB, D) might have a preferential antiviral effect compared with that observed in interferon-induced antiviral signal pathways, such as those of $STAT1\alpha$ and the 6-16 genes. To confirm the results, this study examined whether th signal transduction for the antiviral activity in HepG2 2.2.15 was induced dependently or independently of interferon. To accomplish this, the correlation between the $STAT1\alpha$ and 6-16 genes, and nitric oxide, for the mediation of the antiviral activity was assessed. The increase in nitric oxide in the UDCA groups suggests that the inhibition of viral gene replication was enhanced by the amantadine combinations (AU and AUD), and might be more effective if incubated for longer periods. It was found that $STAT1\alpha$ was activated by the amantadine combination, although to a lesser extent than that of $interferon-\alpha$, and the primary endpoints examined for the inhibition of gene expression (HBsAg and HBcAg) were remarkably well regulated. This suggests that the amantadine triple, or at least the double, combination had better clinical benefits than those of $IFN-\alpha$ and the nucleoside analogue single treatment. This demonstrates that the amantadine combination might be a substitute for the existing HBV therapy if the results of in vivo and in vitro studies concur.

• YAKHAK HOEJI
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• v.42 no.1
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• pp.82-88
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• 1998

The effect of hepatoprotective agents and bile acids on tumor necrosis factor-alpha, (TNF-${\alpha}$) production in murine and human macrophage cell line (RAW264.7 and U937) was inve stigated. The hepatoprotective agents including silymarin and its major component, silybin, significantly inhibited TNF-alpha production in a concentration dependent manner ($IC_50$ of silybin=67.7${\mu}g$/ml (140.3${\mu}g$M)). In differentiated U937 cells, especially, silybin showed more effective inbitory activity ($IC_50$=35.1${\mu}g$g/ml (72.7${\mu}g$M)). These results suggest that silymarin and silybin may inhibit TNF-alpha production in the process of hepatic diseases in human. However, biphenyldimethyl dicarboxylate (DDB) was not effective. In the case of bile acids, chenodeoxycholic acid (CDCA) showed a concentration dependent inhibitory effect on TNF-alpha production ($IC_50$ of CDCA= 71.5${\mu}g$g/ml (182.1${\mu}g$M)). In contrast, glycine or taurine conjugated form (G-CDCA or T-CDCA) restored to the control level or significantly increased TNF-${\alpha}$ production. And also ursodeoxycholic acid (UDCA) and its conjugated forms (G-UDCA and T-UDCA) showed a variety of patterns on TNF-${\alpha}$ production by changes of functional groups and concentration. These results also indicate that bile acids may regulate TNF-${\alpha}$ production in normal hepatic function or disease conditions.

• Food Science and Biotechnology
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• v.17 no.3
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• pp.598-602
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• 2008

Concentrated catfish Silurus asotus bile (SAB) containing high amounts of ursodeoxycholic acid (UDCA) and taurocholic acid may have immunosuppressive properties. To investigate the putative immunosuppressive properties of SAB, the anti-proliferation and suppression of early T cell activation markers, and the inhibition of cytokines induced by T cells in response to anti-CD3 mAb activation in mouse splenocytes were examined. The suppression of these activation repertoires are the main properties of calcineurin inhibitors. It was found that SAB effectively suppressed the activation of T cells, and cytokines from T cell activation, at levels similar to cyclosporine A, a calcineurin inhibitor. Although the mechanism in which suppression occurs is not clear, we speculate that SAB from Silurus asotus, which has been known to switch their intake habits to zoophagy during an early adult stage, may explain the suppressive effect of SAB as a result of high amounts of functional UDCA in bile. Our results suggest that the treatment or intake of SAB, either in therapy or as a food supplement, may act as an adjuvant therapy for the prevention of transplant rejection, although further investigation is required before this treatment can be applied clinically.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.23 no.5
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• pp.430-438
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• 2020

Purpose: We investigated the clinical features and factors affecting the choice of treatment modality and the course of pediatric gallstone (GS) disease. Methods: We retrospectively analyzed the medical records of 65 patients diagnosed with GS using imaging studies between January 2009 and December 2017 were included. Results: This study included 65 patients (33 boys and 32 girls; mean age, 8.5±5.3 years; range, 0.2-18 years) who primarily presented with abdominal pain (34%), jaundice (18%), and vomiting (8%). Idiopathic GS occurred in 36 patients (55.4%). The risk factors for GS included antibiotic use, obesity, hemolytic disease, and chemotherapy in 8 (12.3%), 7 (10.8%), 6 (9.2%), and 4 patients (6.2%), respectively. We observed multiple stones (including sandy stones) in 31 patients (47.7%), a single stone in 17 (26.2%), and several stones in 17 (26.2%). GS with a diameter of <5 mm occurred in 45 patients (69.2%). Comorbidities included hepatitis, choledocholithiasis, cholecystitis, and acute pancreatitis in 20 (30.8%), 11 (16.9%), 11 (16.9%), and 4 patients (6.2%), respectively. Ursodeoxycholic acid (UDCA) was administered to 54 patients (83.1%), leading to stone dissolution in 22 patients (33.8%) within 6 months. Cholecystectomy was performed in 18 patients (27.7%) (mean age, 11.9±5.1 years). Most patients treated surgically had multiple stones (83%) and stones measuring <5 mm in size (89%), and 66.7% of patients had cholesterol stones. Conclusion: Cholecystectomy is feasible in patients with small-sized or large numbers of GS and those with persistent abdominal pain and/or jaundice. UDCA administration with close follow-up is recommended in patients with uncomplicated GS.

• Archives of Pharmacal Research
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• v.27 no.9
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• pp.954-960
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• 2004

Expression of the NF-$textsc{k}$B-dependent genes responsible for inflammation, such as TNF-$\alpha$, IL-1$\beta$, and nitric oxide synthase (NOS), contributes to chronic inflammation which is a major cause of neurodegenerative diseases (i.e. Alzheimer＇s disease). Although NF-$textsc{k}$B plays a biphasic role in different cells like neurons and microglia, controlling the activation of NF-$textsc{k}$B is important for its negative feedback in either activation or inactivation. In this study, we found that ursodeoxycholic acid (UDCA) inhibited I$textsc{k}$B$\alpha$ degradation to block expression of the NF-$textsc{k}$B-dependent genes in microglia when activated by $\beta$-amyloid peptide (A$\beta$). We also showed that when microglia is activated by $A\beta$42, the expression of A20 is suppressed. These findings place A20 in the category of ' protective ' genes, protecting cells from pro-inflammatory reper-toires induced in response to inflammatory stimuli in activated microglia via NF-$textsc{k}$B activation. In light of the gene and proteins for NF-$textsc{k}$B-dependent gene and inactivator for NF-$textsc{k}$B (I$textsc{k}$B$\alpha$), the observations now reported suggest that UDCA plays a role in supporting the attenuation of the production of pro-inflammatory cytokines and NO via inactivation of NF-$textsc{k}$B. Moreover, an NF-$textsc{k}$B inhibitor such as A20 can collaborate and at least enhance the anti-inflammatory effect in microglia, thus giving a potent benefit for the treatment of neurodegenerative diseases such as AD.uch as AD.

• The Korean Journal of Nuclear Medicine
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• v.25 no.1
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• pp.53-60
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• 1991

Extracorporeal shock wave lithotripsy (ESWL) with adjunctive oral litholytic therapy has proven to be a useful treatment in selected patients with gallbladder stones. To study the effect of ESWL on gallbladder dynamics, $^{99m}Tc-DISIDA$ hepatobiliary scintigraphy was done for 25 patients with symptomatic gallstones and 10 normal controls. Of these 25 patients, 15 were treated with ESWL and adjunctive oral litholytic agents (ESWL group) and 10 were treated only with oral litholytic agents (UDCA group). After overnight fast and gallbladder visualization on a routine hepatobiliary scintigraphy with 7mCi of $^{99m}Tc-DISIDA$, subjects were given fatty meal and imaged with a gamma camera interfaced to a computer (1 frame/minute for 70 minutes). A gallbladder time-activity curve was generated and latent period (LP), ejection period (EP), ejection fraction (EF) and ejection rate (ER) were calculated. ESWL group were studied before, 1day after and 2weeks after ESWL, and WDCA group were studied before and 2weeks after starting oral medication. Mean basal EF was significantly reduced in patients but other parameters were not reduced. In ESWL group, mean EF and mean ER at lday after ESWL were reduced. In 3 of them, gallbladder was not visualized at all. Two weeks after ESWL, however, all parameters were recoverd to basal level. In UDCA group, all parameters were not changed significantly during medication. We can conclude that ESWL has such immediate adverse effect on gallbladder dynamics as reducing contractility and nonvisualization of gallbladder but it has no long-term effect.

• The Journal of Internal Korean Medicine
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• v.44 no.5
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• pp.1011-1016
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• 2023

We have experienced a case in which herbal medicine was administered to treat drug-induced liver damage and would like to introduce it. A 49-year-old man exhibited a positive result in the interferon-gamma release assay. He had never suffered from tuberculosis in the past, and the route and time of infection could not be confirmed. He had no respiratory or systemic symptoms suggestive of active tuberculosis, and a chest X-ray examination showed no active lung lesions, so he was diagnosed with latent tuberculosis infection. He was confirmed to be within the normal range in the liver function test, renal function test, and complete blood cell count test, and started taking rifampin (600 mg qd). In the screening test performed on the 19th day of taking the drug, other test items were normal, but alanine aminotransferase (ALT) increased to 50 U/L (reference value: 4-40 U/L). In a test performed on the 29th day of taking the drug, ALT was clearly elevated to 102 U/L. Ursodeoxycholic acid and Injinho-tang were taken together with rifampin, and the patient's progress was observed. In a test performed 14 days later, ALT decreased to 26 U/L, within the normal range. It is presumed that Injinho-tang may have partially contributed to alleviating liver damage in this case.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.245.2-246
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• 2002

We studied on the antiproliferative effects of bile acids and their derivatives on HepG2 human hepatocellular carcinoma cells. Ursodeoxycholic acid (UDCA) and its synthetic derivative HS-1030. and chenodeoxycholic acid (CDCA) and its synthetic derivatives. HS-1199 and HS\ulcorner200, were used. We focused on the regulation of cell cycle and induction of apoptosis by these bile acid derivatives. (omitted)

• Biomolecules & Therapeutics
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• v.6 no.2
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• pp.119-129
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• 1998

The dose-response effect of polysaccharide extracts(PS-1) from Artemisia iwayomogi was inves-tigated under various hepatic disease models. Silymarin, DDB and UDCA were used as reference compounds. We found that the maximal effective dose of PS-1 was 100 mg/kg b.wt. in $CCl_4$-induced hepatotoxicity, D-galactosamine-induced hepatitis, in ANIT-induced cholestasis and 300 mg/kg b.wt. in $CCl_4$-induced chronic liver disease, 30 mg/tg b.wt. in chronic bile duct ligation and chronic ethanol fatty liver. These findings suggest that PS-1 fraction protects the hepatocyte against various hepatic injuries, and this fracton might be of therapeutic value.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.208.1-208.1
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• 2003

In recent, growing aged people in coupled with the increased senile dementia, Alzheimer's disease, has been a social interests to be cleared out. Alzheimer Disease(AD), first reported by Alios Alzheimer (1864-1915) in 1907, is a neurodegenrative disease. Nothing exact cause of AD is available by now, but in clinical founding ${\beta}$-amyloid peptide(A${\beta}$) and microtubule associated protein($\tau$ protein) is to involved in the disease, and the most important feature in AD is Known to induce chronic inflammation to neuron cell. (omitted)