• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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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)

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.246.1-246.1
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• 2002

We studied the effects of ursodeoxycholic acid (UDCA) and its synthetic derivatives. HS-l030 and HS-1183. and chenodeoxycholic acid (CDCA) and its synthetic derivatives, HS-1199 and HS-1200. on the human colon adenocarcinoma cell line. HT -29 (p53 mutant type). The effects on cell viability and growth were assessed by MTT assay and cell growth study. While UDCA and CDCA exhibited no significant effect, their novel derivatives inhibited the proliferation of HT-29 cell line in a concentration- and time-dependent manners. (omitted)

• Biomolecules & Therapeutics
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• 제16권2호
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• pp.126-131
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• 2008

Immunosuppressive therapy after organ transplantation is routinely used to prevent rejection of the organ, because this decreases the risk of adverse events, infection, and malignancies. Recently, ursodeoxycholic acid (UDCA), which is isolated from the dried bile of adult Chinese bears, has been shown to reduce the incidence and severity of acute rejection of liver allograft during early phase of liver transplantation. Therefore, in this study, we investigated the effect of UDCA on the proliferation of splenocytes exposed to PMA plus ionomycin. Our results demonstrated that UDCA decreased the splenocytes' proliferation in a dose-dependent manner. The decreased cell proliferation was accompanied with the decreased secretion of cytokines such as IL-2, IFN-${\gamma}$ and TNF-${\alpha}$. In addition, the pretreatment of UDCA on splenocytes stimulated with PMA plus ionomycin decreased the mRNA levels of cytokines (IL-2, IFN-${\gamma}$ and TNF-${\alpha}$) and costimulatory molecules (B7.2 and PD-L1). These results suggest the beneficial effect of UDCA on organ transplantation by decreasing lymphocyte proliferation.

• Archives of Pharmacal Research
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• 제28권4호
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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.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.229.1-229.1
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• 2003

The anti proliferative effects of bile acids and their derivatives on HT -29 human colon cancer cells were investigated. Ursodeoxycholic acid (UDCA) and its synthetic derivatives, HS-1030 and HS-1183, and chenodeoxycholic acid (CDCA) and its synthetic derivatives, HS-1199 and HS-1200 were employed for this study. General evaluations focusing on cell cycle were conducted in HT -29 human colon adenocarcinoma cell line (p53 mutant type). (omitted)

• The Korean Journal of Physiology and Pharmacology
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• 제1권1호
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• pp.107-115
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• 1997

We studied the effects of bile acids on the induction ofapoptosis in HepG2 human hepatocellular carcinoma cells. Treatment with either ursodeoxycholic acid (UDCA) or lithocholic acid (LCA) resulted in a dose- and time-dependent decrease in cell viability assessed by MTT assay. Both UDCA and LCA also induced genomic DNA fragmentation, a hallmark of apoptosis, indicating that the mechanism by which these bile acids induce cell death was through apoptosis. Cycloheximide, a protein synthesis inhibitor, blocked the apoptosis induced by these bile acids, implying that new protein synthesis may be required for the apoptosis. Intracellular $Ca^{2+}$ release blockers (dantrolene and 3,4,5-trimethoxybenzoic acid-8-(diethylamino)octyl ester) inhibited decreased cell viability and DNA fragmentation induced by these bile acids. Treatment of HepG2 cells with calcium ionophore A23l87 induced DNA fragmentation. These results suggest that UDCA and LCA induce apoptosis in the HepG2 cells and that the activation of intracellular $Ca^{2+}$ signals may play an important role in the apoptosis induced by these bile acids.

• 한국식품과학회지
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• 제38권3호
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• pp.452-455
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• 2006

퇴행성뇌질환인 치매의 정확한 원인은 아직 불분명하나 빠른 뇌세포사멸이 주요한 원인으로 알려져 있다. 특히, 알츠하이머형 치매는 다량 생성되는 활성산소에 의한 뇌세포사멸이 주요원인인 것으로 입증되고 있다. 따라서 본 연구에서는 웅담활성성분인 UDCA의 세포보호 및 항산화효과로부터 알츠하이머형 치매와 같은 퇴행성 뇌질환억제 또는 치료물질로서의 가능성을 입증하고자 하였고 뇌의 대식세포인 소교세포(microglia)를 cell model로 하였다. MTT 실험결과 UDCA에 의한 세포보호효과는 $7.5\;{\mu}g/mL$ 주변 농도에서 관찰되었고 NO에 의한 세포손상 유도억제효과를 확인하였다(Fig. 2). 이와 같은 결과는 형광현미경하에서 보다 명확히 관찰되어(Fig. 3) 결국 UDCA에 의한 항세포사효과가 있음을 알 수 있었다. UDCA의 항산효과는 활성산소인 $H_2O_2$의 단백질 분해 저해능을 관찰하는 금속이온촉매 산화효과를 통해 확인하였다(Fig. 4). 즉, UDCA는 농도의존적으로$(1{\sim}100\;{\mu}g/mL)$ 단백질 분해억제능을 보였으며 $100\;{\mu}g/mL$ 이상의 농도에서 양성대조군인 ascorbic acid와 유사한 억제효과를 나타냈다. 이와 같은 UDCA의 항산화효과는 $10\;{\mu}g/mL$ 전후에서 관찰되어 세포보호효과를 나타내는 농도$(7.5\;{\mu}g/mL)$와 큰 차이가 없는 것으로 사료되었고 따라서 UDCA의 농도범주는 일괄적 적용이 가능할 것으로 판단된다. 결론적으로 웅담활성성분인 UDCA는 일반적으로 사용하여온 간질환 및 소화계질환의 보조요법제의 개념을 벗어나 항염 및 항산화효과에 잠재능을 가지며 나아가 뇌신경세포를 보호하고 세포사를 차단하여 알츠하이머와 같은 퇴행성뇌질환 조절 후보물질로 적용이 가능할 것으로 판단되나 보다 심도 있는 in vivo 및 임상적 차원의 연구가 요구된다.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제17권2호
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• pp.121-124
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• 2014

Omega (${\omega}$)-3 polyunsaturated fatty acids appear to be effective in preventing and treating parenteral nutrition-associated liver disease, and several mechanisms were proposed for this observation. An 8-week-old male infant with cholestasis and acholic stool was diagnosed non-syndromic intrahepatic interlobular bile duct paucity by open-wedge liver biopsy. Initially he was treated with usual supportive medical therapy, including ursodeoxycholic acid. However, the clinical status and laboratory tests did not improve. Omega (${\omega}$)-3 polyunsaturated fatty acids (initially intravenous administration and oral administration later), were started and his liver function, including aminotransferase level and bilirubin levels normalized, and the ivory stool color turned green. We report the possible effectiveness of ${\omega}$-3 polyunsaturated fatty acids as a potent choleretic agent for non-syndromic intrahepatic interlobular bile duct paucity, a very rare structural pediatric hepatic disease.

• Biomolecules & Therapeutics
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• 제2권2호
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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.

• Journal of Yeungnam Medical Science
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• 제39권3호
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• pp.256-261
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• 2022

Sarcoidosis often involves the liver. However, primary hepatic sarcoidosis confined to the liver without evidence of systemic involvement is rare. We report the case of a 37-year-old man with hepatic sarcoidosis who initially presented with elevated liver enzymes and suspicious cirrhotic nodules on computed tomography. The patient had cirrhosis but did not have portal hypertension. Based on the initial histopathologic finding of chronic granulomatous inflammation and the common clinical characteristics of sarcoidosis, he was initially diagnosed with primary biliary cholangitis, and his daily dosage of ursodeoxycholic acid was increased to 900 mg. After 14 months of treatment, his total serum bilirubin concentration was 10.9 mg/dL (upper normal limit, 1.2 mg/dL). Additionally, a transjugular liver biopsy revealed multiple noncaseating granulomas. He was diagnosed with primary hepatic sarcoidosis involving the lungs, heart, spleen, kidneys, and skin. Treatment with methylprednisolone was initiated. Two weeks later, he was started on azathioprine, and the dose of steroid was simultaneously reduced. These findings indicate the importance of including hepatic sarcoidosis as a possible diagnosis in patients with elevated liver enzymes or cryptogenic cirrhosis.