• 약학회지
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• 제38권1호
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• pp.78-85
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• 1994

From phase solubility studies bile acids and bile salts were found to form stable inclusion complexes with ${\beta}-cyclodextrin$ in aqueous solution. Stability constant of bile acids were larger than that of bile salts. Phase solubility diagrams of most bile acids showed Higuchi's $A_I$ type but lithocholic acid showed $B_S$ type. Not only the solubility of bile acids but also that of ${\beta}-cyclodextrin$ increased, especially in cases of cholic acid and ursodeoxycholic acid. Solubility increase of bile acids from their ${\beta}-cyclodextrin$ inclusion complex followed the order : cholic acid>ursodeoxycholic acid>chenodeoxycholic acid>deoxycholic acid>lithocholic acid. It seems that solubility of inclusion complexes was directly related with the hydrophilicity of bile acids.

• 한국임상약학회지
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• 제28권4호
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• pp.273-278
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• 2018

Bile acids are major constituents of bile and known to help absorb dietary fat and fat-soluble vitamins in the gastrointestinal tract. In the past few decades, many studies have shown that bile acids not only play a role in fat digestion but also function as broad range of signal transduction hormones by binding to various receptors present in cell membranes or nuclei. Bile acid receptors are distributed in a wide range of organs and tissues in the human body. They perform multitudes of physiological functions with complex mechanisms. When bile acids bind to their receptors, they regulate fat and glucose metabolism in a tissue-specific way. In addition, bile acids are shown to inhibit inflammation and fibrosis in the liver. Considering the roles of bile acids as metabolic regulators, bile acids and their receptors can be very attractive targets in treating metabolic disorders. In the future, if roles of bile acids and their receptors are further clarified, they will be the novel target of drugs in the treatment of various metabolic diseases.

• 한국미생물·생명공학회지
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• 제50권1호
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• pp.102-109
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• 2022

Bile acids are essential molecules produced by vertebrates that are involved in several physiological roles, including the uptake of nutrients. Bacterial isolates capable of producing bile acids de novo have been identified and characterized. Such isolates may provide access to novel biochemical pathways suitable for the design of microbial cell factories. Here, we further characterized the ability of Maribacter dokdonensis, Dokdonia donghaensis, and Myroides pelagicus to produce bile acids. Contrary to previous reports, we did not observe de novo production of bile acids by these isolates. Instead, we found that these isolates deconjugated the amino acid moiety of bile acids present in the growth medium used in previous reports. Through genomic analysis, we identified putative bile salt hydrolases, which could be responsible for the different bile acid modifications observed. Our results challenge the hypothesis of de novo microbial bile acid production, while further demonstrating the diverse capacity of bacteria to modify bile acids.

• 한국임상약학회지
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• 제21권2호
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• pp.49-56
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• 2011

The family of bile acids belongs to a group of molecular species of acidic steroids with very peculiar biological characteristics. They are synthesized by the liver from cholesterol through several complementary pathways and secreted into small intestine for the participation in the digestion and absorption of fat. The bile acids are mostly confined to the territories of the so-called enterohepatic circulation, which includes the liver, the biliary tree, the intestine and the portal blood with which bile acids are returned to the liver. In patients with bile acid malabsorption, the amount of primary bile acids in the colon is increased compared to healthy controls. Although the increase in the secondary bile acids including deoxycholic acid, is reported to have the potency to affect tumorigenesis in gastrointestinal tracts, there is no firm evidence that clinically relevant concentrations of the bile acids induce cancer. The list of their physiological roles, as well as that of the pathological processes is long and still not complete. There is no doubt that many new concepts, pharmaceutical tools and pharmacological uses of bile acids and their derivatives will emerge in the near future.

• 약학회지
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• 제31권2호
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• pp.105-111
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• 1987

A high performance liquid chromatographic method was developed for the simultaneous determination of free and glycine conjugated bile acids. Free and glycine conjugated bile acids were extracted from bear gall bladder by methanol and from serum using a Sep-pak $C_{18}$ catridge. The extracted bile acids were labeled with 2-bromoacetyltriphenylene in acetonitrite using 18-crown-6-ether as a catalyst. Derivatized bile acids were separated from the individual bile acids on a reversedphase column (Chemcosorb 5-ODS-H) using acetonitrile-methanol-water(10:50:30) as a mobile phase and monitored by an UV-detector at 254nm. Linearities of calibration curve were obtained between 4 ng and 24 ng, and recoveries from bear gall bladder sample were higher than 94%.

• Journal of Pharmaceutical Investigation
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• 제21권2호
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• pp.67-71
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• 1991

A simple and sensitive method was developed for the quantification of free and conjugated bile acids in bezoar without prior hydrolysis. $3{\alpha}-Hydroxy$ bile acids are first oxidized to 3-keto bile acids in the reaction catalyzed by $3{\alpha}-hydroxysteroid$ $dehydrogenase(3{\alpha}-HSD)$. During this oxidative reaction, an equimolar quantity of nicotinamide adenine dinucleotide(NAD) is reduced to NADH and subsequently oxidized to NAD with concomitant reduction of nitrotetrazolium blue(NTB) to diformazan by the catalytic action of diaphorase. The diformazan has an absorbance maximum at 540 nm. The intensity of the color produced is directly proportional to bile acids concentration in the bezoar extracts. The optimum conditions for the enzymatic reaction such as effects of reaction time, reaction temperature and pH, and stability were investigated. Calibration plots for the sodium chelate observed to be linear and intra-, inter-assay analytical recovery of bile acids averaged $97.65{\pm}3.4%(S.D.)$. Therefore, it is considered that the quality control of total bile acids from bezoar or bezoar-containing liquid preparation using this simple and sensitive assay system will be acceptable. Also current bezoars and bezoar-containing liauid preparations were examined their total bile acids from this method.

• 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.

• BMB Reports
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• 제29권1호
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• pp.68-72
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• 1996

Ursodeoxycholic acid (UDCA) and lithocholic acid (LCA), secondary bile acids, have been shown to have a cell differentiation activity in mouse F9 teratocarcinoma stem cells. Treatment with bile acids induced morphological changes, including cytoplasmic and nuclear membrane blebbing, aggregation of organelles, and chromatin condensation, corresponding to apoptosis. Moreover, the bile acids induced intemucleosomal DNA fragmentation, a hallmark of apoptosis. In addition, the expression of c-jun was increased, but that of c-myc and laminin was decreased during apoptosis induced by the bile acids in F9 cells. These results suggest that the bile acids can induce apoptosis in F9 cells. Furthermore, the c-jun expression may be related to the apoptosis induced by UDCA or LCA in F9 cells.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제2권1호
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• pp.59-64
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• 1999

목 적: 저자들은 백서에서 수술적으로 담도 결찰전과 결찰 4주 후에 지용성 비타민(vitamin A와 D)의 혈중 농도 변화 및 담도 결찰 후 담즙산을 투여했을 때 장관내 지용성 비타민의 흡수 변화에 대하여 알아보고자 하였다. 대상 및 방법: 생후 4주된 Sprague-Dawley rats을 대상으로 하여 수술적으로 담도를 결찰하였다. 담도 결찰 전과 결찰 4주후의 혈중 ALT, total bilirubin, vitamin A, vitamin D의 농도를 측정하였다. 백서들은 담도 결찰 후 4주간 사육하였으며, 사육기간 중 비타민만을 투요한 군, 담즙산을 투여한 군 및 UDCA를 투여한 3군으로 나누었다. 결 과: 1) 수술전 혈중 농도(평균): ALT 74.2 IU, total bilirubin 0.26 mg/dL; vitamin D 13.01 ng/mL vitamin A $0.87\;{\mu}g/mL$, total bile acids $25.16\;{\mu}mol/L$. 2) 수술 4주후 농도(평균): ALT 100.7 IU, total bilirubin 2.58 mg/dL; vitamin D 7.89 ng/mL vitamin A $1.37\;{\mu}g/mL$, total bile acids $278.22\;{\mu}mol/L$. 3) 수술후 각 군간의 혈중 vitamin A와 vitamin D의 농도 차이는 없었다. 결 론: 담도 결찰 후 vitmain A 혈중 농도는 상승 하였으며, vitamin D 농도는 감소하였다. 경구로 담즙산을 투였을 때 혈중 지용성 vitamin 농도는 투여하지 않은 경우와 차이가 없었다.

• The Korean Journal of Physiology and Pharmacology
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• 제4권4호
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• pp.333-338
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• 2000

We have examined whether bile acids can affect the electrical and mechanical activities of circular smooth muscle of canine colon and ileum, using isometric tension measurement or patch clamp technique. It was found that a dilution of canine bile $(0.03{\sim}2%\;by\;volume)$ enhanced or inhibited the amplitude of spontaneous contractions. An individual component of bile, deoxycholic acid (DCA) enhanced the frequency and amplitude of the spontaneous contractile activity at $10^{-6}\;M,$ while DCA at $10^{-4}\;M$ inhibited the contraction. Similarly, the response to cholic acid was excitatory at $10^{-5}\;M$ and inhibitory at $3{\times}10^{-4}\;M.$ Taurocholic acid at $10^{-4}\;M$ enhanced the amplitude of muscle contraction. Electrically, canine bile at 1% reversibly depolarized the colonic myocytes under current clamp mode. Bile acids also elicited non-selective cation currents under voltage clamp studies, where $K^+$ currents were blocked and the $Cl^-$ gradient was adjusted so that $E_{Cl}^-$ was equal to -70 mV, a holding potential. The non-selective cation current might explain the depolarization caused by bile acids in intact muscles. Furthermore, the bile acid regulation of electrical and mechanical activities of intestinal smooth muscle may explain some of the pathophysiological conditions accompanying defects in bile reabsorption.