• Molecules and Cells
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• v.38 no.10
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• pp.851-858
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• 2015

Disturbed blood flow with low-oscillatory shear stress (OSS) is a predominant atherogenic factor leading to dysfunctional endothelial cells (ECs). Recently, it was found that disturbed flow can directly induce endoplasmic reticulum (ER) stress in ECs, thereby playing a critical role in the development and progression of atherosclerosis. Ursodeoxycholic acid (UDCA), a naturally occurring bile acid, has long been used to treat chronic cholestatic liver disease and is known to alleviate endoplasmic reticulum (ER) stress at the cellular level. However, its role in atherosclerosis remains unexplored. In this study, we demonstrated the anti-atherogenic activity of UDCA via inhibition of disturbed flow-induced ER stress in atherosclerosis. UDCA effectively reduced ER stress, resulting in a reduction in expression of X-box binding protein-1 (XBP-1) and CEBP-homologous protein (CHOP) in ECs. UDCA also inhibits the disturbed flow-induced inflammatory responses such as increases in adhesion molecules, monocyte adhesion to ECs, and apoptosis of ECs. In a mouse model of disturbed flow-induced atherosclerosis, UDCA inhibits atheromatous plaque formation through the alleviation of ER stress and a decrease in adhesion molecules. Taken together, our results revealed that UDCA exerts anti-atherogenic activity in disturbed flow-induced atherosclerosis by inhibiting ER stress and the inflammatory response. This study suggests that UDCA may be a therapeutic agent for prevention or treatment of atherosclerosis.

• Korean Journal of Pharmacognosy
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• v.15 no.3
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• pp.139-146
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• 1984

High performance liquid chromatographic separation is described for the analysis of bile acids after hydrolysis in seven commercial crude bile drugs and ox and pig galls. They are simultaneously separated with HPLC mobile phase of acetonitrile/0.5% ammonium carbonate (pH 6.7) (25.5 : 74.5) at a flow rate $(1.0{\rightarrow}1.5ml/min.)$ and differential refractometer. The linearity of calibration curve and recovery test are good by using the method. The analysis of major bile acids in seven commercial crude bile drugs using the described method is presented. Sample no. 1 of them is similar to separation pattern of ox gall. Sample no. 6 of them is supposed to be genuine bear gall on the basis of identification of ursodeoxycholic acid. Sample $no.\;2{\sim}5$ and 7 of them are supposed to be pig gall on the basis of identification of hyodeoxycholic acid which is a characteristic component of pig gall.

• Proceedings of the PSK Conference
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• 2000.04a
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• pp.209.1-209.1
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• 2000

• 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.

• Korean Journal of Clinical Pharmacy
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• v.15 no.1
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• pp.9-20
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• 2005

Cholestatic liver disease is a frequent complication of prolonged parenteral nutrition, especially in premature infants. Numerous factors have been cited as contributing to TPN associated cholestasis. However the exact etiology remains obscure. Ursodeoxycholic acid (UDCA) has been reported to be beneficial far children and adults with various chronic cholestatic liver disease. The aim of this prospective, randomized, double-blind, placebo-controlled study was to determine the preventive effects of UDCA administration during TPN. Seventeen pediatric patients (8 boys and 9 girls) undergoing TPN were assigned randomly to two groups, UDCA and placebo group. UDCA group (n=9) received 15 mg/kg/day UDCA and placebo group (n=8) received 15 mg/kg/day placebo enterally during the TPN period. Liver function tests (total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase) were per-formed before TPN and weekly or three times a week. The patients' weights, complete blood count, composition of TPN, and the infusion rate of TPN and lipid were monitored everyday. Calcium and phosphate were monitored twice a week. Between the UDCA and placebo groups, there were no differences in weight at the onset of TPN, birth weight, duration of TPN, respiratory distress syndrome associated with prematurity, age at the onset of TPN, gestational age, the number of days the patients received antibiotics, the number of patients received enteral nutritions and the composition of TPN. In contrast, there was a significant difference between the UDCA and placebo groups in alanine aminotransferase levels during TPN. It doesn't seem that UDCA administration during TPN correlates directly with improvement of liver function. But the preventive administration of UDCA may be effective in reducing liver enzyme, alanine aminotransferase and has no adverse effects.

• Journal of Periodontal and Implant Science
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• v.26 no.4
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• pp.1013-1021
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• 1996

There are many important factors in periodontal inflammation. $IL-1{\beta}$, $PGE_2$ and collagenase are predorminantly key factors. These inflammatory mediators induce gingival tissue and alveolar bone destruction. For the prevention and treatment of periodontal disease, it is necessary to inhibit $IL-1{\beta}$, $PGE_2$ production and collagenase activity. Ursodeoxycholic acid(UDCA) has immunomodulatory properties, and there is evidence that some natural extracts show antiinflammatory activity to some degree. The purpose of this study was to assess the inhibitory effect of UDCA and its mixture with natural extracts on $IL-1{\beta}$, $PGE_2$ production and collagenase activity. Accordingly we assessed the effect of UDCA and its mixture combined with some natural extracts on inhibition of $IL-1{\beta}$, $PGE_2$ production and collagenase activity. For the $IL-l{\beta}$ inhibition study, cultured cells were exposed to $25{\mu}g/ml$ LPS. $IL-1{\beta}$ activity was measured by $IL-1{\beta}$ enzyme immunoassay system. Human gingival fibroblasts were prepared and cells (l05/well) were seeded into culture plates. $rhIL-1{\beta}$ was added to induce $PGE_2$. The amount of $PGE_2$ in sample media was measured using enzyme immunoassay system. Crude collagenase was prepared from Porphyromonas gingivalis and collagenolytic activity was determined using a Collageno kit CLN-100. The test inhibitor was added to the assay mixture consisting of 0.1ml of 50mM Tris buffer(pH 7.5) and 0.2ml of substrate solution. UDCA and UDCA combined with natural extracts generally inhibited $IL-1{\beta}$ production. groups above 0.01% UDCA strongly inhibited $IL-l{\beta}$ synthesis. Both groups inhibited $IL-1{\beta}-induced$ synthesis of $PGE_2$. In low concentration, the degree of inhibition was as same as prednisolone. In high concentration, each group was superior to prednisolone. UDCA group and UDCA mixture group exerted a moderate inhibition of collagenolytic enzyme. The present study suggested that UDCA and its mixture with natural extracts could be further investigated as antiinflammatory drug for periodontal disease.

• 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.

• Archives of Pharmacal Research
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• v.20 no.1
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• pp.29-33
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• 1997

The effects of ursodeoxycholic acid (UDCA) and its novel derivative, named as HS-1030, on the proliferation of HepG2, human hepatocellular carcinoma cells were investigated. Whereas UDCA had no significant effect in a concentration range we have tested, HS-1030 inhibited the proliferation of HepG2 cells in a concentration dependent manner. Surprisingly, HS-1030 had no effect on the proliferation of Human Chang liver cell which is a normal liver cell line. We also found that proliferation-inhibitory effect of HS-1030 was due to the induction of apoptosis of HepG2 cells, which was confirmed by observing the internucleosomal DNA fragmentation and morphological changes (ie., cell shrinkage, nuclear condensation and the formation of apoptotic bodies). These results suggest that HS-1030 may be a good candidate as a drug for the treatment of liver cancer.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.18 no.3
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• pp.202-208
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• 2015

Progressive familial intrahepatic cholestasis type 3 (PFIC3) is an autosomal recessive disorder of cholestasis of hepatocellular origin, typically seen in infancy or childhood caused by a defect in the ABCB4 located on chromosome 7. Here we report on an older patient, aged 15, who presented with biochemical testing that led to an initial consideration of a diagnosis of Wilson disease (WD) resulting in a delayed diagnosis of PFIC3. Diagnosis of PFIC3 was later confirmed by molecular studies that identified novel mutations in the ABCB4 gene. Cholestasis due to PFIC3 can cause elevated hepatic copper and increased urine copper excretion that overlap with current diagnostic criteria for WD. Molecular diagnostics are very useful for establishing the diagnosis of PFIC3. Ursodeoxycholic acid ameliorates cholestasis in PFIC3, and may help mediate a reduction in hepatic copper content in response to treatment.

• YAKHAK HOEJI
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• v.46 no.2
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• pp.102-107
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• 2002

The particle size of medicinal materials is an important physical property which affects the pharmaceutical behaviors such as dissolution, chemical stability, compressibility and bioavailability of solid dosage forms. The size reduction of raw pharmaceutical powder is needed to formulize insoluble drugs or slightly soluble drugs and to improve the pharmaceutical properties such as the solubility, the pharmaceutical mixing and the dispersion. The objective of the present study is to evaluate the grinding characteristics of ursodeoxycholic acid(UDCA) as a model of insoluble drugs. The effects of the grinding time and the amount of additive on particle size distribution of ground UDCA were investigated. Grinding of insoluble drug, UDCA and a series of dry co-grinding experiments of UDCA with sodium lauryl sulfate(SLS) as an additive were carried out using a planetary ball mill. It was measured that the median diameter and the particle size distribution of ground products with grinding UDCA and additive SLS by Mastersizer. As a result of co-grinding of UDCA and SLS, the particle size of co-grinding products was decreased more than single grinding one. However, it was observed that co-grinding products were reaggregated to larger particles after 120 min.