• Title/Summary/Keyword: Cholic acid

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Bile Acid Modulation of Gastroinstinal Smooth Muscle Contraction and Ionic Currents

  • Lee, Hye-Kyung;Lee, Kyoung-Hwa
    • The Korean Journal of Physiology and Pharmacology
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    • v.4 no.4
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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.

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Integrative Omics Reveals Metabolic and Transcriptomic Alteration of Nonalcoholic Fatty Liver Disease in Catalase Knockout Mice

  • Na, Jinhyuk;Choi, Soo An;Khan, Adnan;Huh, Joo Young;Piao, Lingjuan;Hwang, Inah;Ha, Hunjoo;Park, Youngja H
    • Biomolecules & Therapeutics
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    • v.27 no.2
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    • pp.134-144
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    • 2019
  • The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased with the incidence of obesity; however, the underlying mechanisms are unknown. In this study, high-resolution metabolomics (HRM) along with transcriptomics were applied on animal models to draw a mechanistic insight of NAFLD. Wild type (WT) and catalase knockout (CKO) mice were fed with normal fat diet (NFD) or high fat diet (HFD) to identify the changes in metabolic and transcriptomic profiles caused by catalase gene deletion in correspondence with HFD. Integrated omics analysis revealed that cholic acid and $3{\beta}$, $7{\alpha}$-dihydroxy-5-cholestenoate along with cyp7b1 gene involved in primary bile acid biosynthesis were strongly affected by HFD. The analysis also showed that CKO significantly changed all-trans-5,6-epoxy-retinoic acid or all-trans-4-hydroxy-retinoic acid and all-trans-4-oxo-retinoic acid along with cyp3a41b gene in retinol metabolism, and ${\alpha}/{\gamma}$-linolenic acid, eicosapentaenoic acid and thromboxane A2 along with ptgs1 and tbxas1 genes in linolenic acid metabolism. Our results suggest that dysregulated primary bile acid biosynthesis may contribute to liver steatohepatitis, while up-regulated retinol metabolism and linolenic acid metabolism may have contributed to oxidative stress and inflammatory phenomena in our NAFLD model created using CKO mice fed with HFD.

Effects of quercetin on the improvement of lipid metabolism through regulating hepatic AMPK and microRNA-21 in high cholesterol diet-fed mice (고콜레스테롤 식이 섭취 쥐에서 quercetin의 간 AMPK 및 microRNA-21 조절을 통한 지질대사 개선 효과)

  • Lee, Mak-Soon;Kim, Yangha
    • Journal of Nutrition and Health
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    • v.55 no.1
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    • pp.36-46
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    • 2022
  • Purpose: Quercetin is a polyphenolic flavonoid abundant in many fruits and vegetables. It has potential health-beneficial properties, such as antioxidant, anti-obesity, anti-cancer, anti-diabetic and anti-inflammatory effects. The purpose of this study was to investigate whether the lipid metabolism improvement effect of quercetin affected the regulation of AMP-activated protein kinase (AMPK) activity and microRNA (miR)-21 expression in the liver of mice fed a high-cholesterol diet. Methods: Male C57BL/6J mice were fed with normal diet, quercetin-free diet and diets containing 0.05% or 0.1% quercetin for six weeks. Hypercholesterolemia was induced by adding 1% cholesterol and 0.5% cholic acid to all diets. Serum and liver triglyceride (TG), and total cholesterol (TC) concentrations were analyzed using a commercial enzymatic colorimetric kit. AMPK activity was quantified using an AMPK kinase assay kit. The levels of miR-21 and genes involved in lipid metabolism were measured by real-time quantitative polymerase chain reaction. Results: Supplementation of quercetin reduced serum and hepatic TG and TC levels without changing body weight and food intake. Dietary quercetin significantly inhibited the mRNA levels of hepatic sterol-regulatory element binding protein-1c, acetyl-CoA carboxylase 1 and fatty acid synthesis, which are involved in hepatic lipogenesis. Dietary quercetin enhanced AMPK activity and suppressed miR-21 expression, promoting hepatic lipid accumulation. Conclusion: These results suggest that the lipid-lowering effect of quercetin on the serum and liver of mice may be partially mediated by the regulation of lipogenic gene expression, AMPK activity and miR-21 expression in the liver of mice fed a high-cholesterol diet.

Effects of Resistant Starch on Metabolism of Beile Acids in College Women (효소저항저분이 인체내 담즙산 대사에 미치는 영향)

  • 김지현;최인선;박소앙;신말식;오승호
    • Journal of Nutrition and Health
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    • v.33 no.8
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    • pp.802-812
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    • 2000
  • The purpose of this study was to examine the effect of resistant starch(RS) in hyperchlesterolemia and colon cancer. The subjects of this study was eight college women participating in the general starch diet(GSD) period for 5 days and resistant starch diet(RSD) period for 7 days. RSD contains 30g or the RS. On the last day of each program blood were collected. And for the last 3 days of each diet period, the amount of all the food consumed by the subjects and feces were collected. Food was measured to determine and compared the energy, protein and fat intakes. The amount of total cholesterol, HDL-cholesterol, LDL-cholesterol and volatile fatty acids in plasma and the amounts of bile acids in feces were measured by gas chromatography. The results obtained were as follows, Daily energy intake was higher in the RSD compared with the GSD, Protein and fat intakes were lower in the RSD compared with the compared with the GSD. Volatile fatty acid contents in plasma, the amounts of acetic acid, propionic acid and valeric acid were higher in the RSD compared with the GSD. The amounts of bile acids in feces, cholic acid, chenodeoxycholic acid and lithocholic acid were higher in the RSD compared with the GSD, But the amount of deoxycholic acid n the RSD period was significantly low. Secondary/primary ratios of bile acids was lower in the RSD compared with GSD, respectively. We speculate that , RS consumption decreases colonic mucosal proliferation as a result of the decreased formation of cytotoxic secondary bile acids. Thus, RS intakes may contribute the prevention of heart disease and colon cancer in humans. (Korean J Nutrition 33(8) : 802-812, 2000)

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26-Hydroxylation of Cholesterol Side Chain in Vertebratss.

  • Kim, Hyun-Gull;Hoshita, Takahiko
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.245-245
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    • 1996
  • (중략) 금번 조사한 양서류 이상의 고등동물에 있어서는 rat를 제외하고 Mt에 있어서의 26-수산화활성이 Ms에서 보다 높았으며, 그 입체 배치도 25R체가 우세하게 생성되었다. 종래, 이 동물종의 연구에 주되게 쓰여져 왔던 rat가 예외적인 존재였다. 한편, 어류에 있어서는 그 결과가 다른 동물종과 큰 차이가 있었다. 즉, 잉어는 Ms의 활성이 Mt에 비해 압도적으로 높았으며 25R체가 대부분 생성되었다. 도미는 어느 fraction에서도 25S체가 극미량밖에 생성되지 않았으며, 송어의 경우 26-수산화활성은 검출되지 않았다. 여기서 송어의 담즙주성분은 cholic acid이며, 이 동물의 경우에는 통상과는 다른 담즙산 생합성경로의 가능성이 시사되었다.

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MECHANISM OF LOWERING OF THE BLOOD CHOLESTEROL LEVEL IN HYPERCHOLESTEROLEMIC RAT BY UL-COMPOUNDS, SN20 AND SQ

  • Kim, Won-Dai;Ha, Jong-Hyun;Park, Young-In;Dong, Mi-Sook
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.05a
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    • pp.142-142
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    • 2001
  • This study was undertaken to explore the effect of SN20 and SQ compounds, which were synthesized by UL-Biotech on the lowering of level of the blood cholesterol by (Seoul, Republic of Korea), and the mechanism of them. The lowering effect of SN20 and SQ on total blood cholesterol were determined in rats fed hyperlipodic powder diets containing 1% cholesterol and 0.5% cholic acid with warious concentrations of SN20 or SQ for 1 week to 4 weeks.(omitted)

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Effect of Suppository Bases on Absorption of Lithium Carbonate (좌제기제가 탄산리튬의 흡수에 미치는 영향)

  • Kim, Yong-Hyun
    • Journal of Pharmaceutical Investigation
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    • v.16 no.4
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    • pp.148-151
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    • 1986
  • This paper was designed to investigate the influence of different suppository bases on both the rectal absorption and dissolution rate of lithium carbonate, and to compare bioavailability from rectal administration with that from oral administration. The dissolution rates were in such order as PEG 4000, surfactant A (Witepsol 15+sodium lauryl sulfate), surfactant B (Witepsol 15+cholic acid), Witepsol 15 and cacao butter. Among various suppository bases, the blood level of lithium carbonate after rectal administration was increased in the following order: surfactant A>surfactant B>PEG 4000>Witepsol 15>cacao butter. When it comes to compare oral with rectal administration in AUC values, surfactants and PEG 4000 showed similar blood levels to oral administration, but lipophilic bases such as Witepsol 15 and cacao butter showed far lower blood level than oral administration. Peak time in oral administration was 2 hrs, but those in rectal administration using various suppository bases were $6{\sim}8$ hrs.

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The Serum Cholesterol Level Lowering Effect from the Underground Parts of Rosa rugosa (해당화 지하부의 혈청 Cholesterol치 저하효과)

  • 양한석;박종철;최재수;정해영
    • YAKHAK HOEJI
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    • v.31 no.6
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    • pp.394-398
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    • 1987
  • The present paper describes the serum cholesterol level lowering effect of the underground parts of Rosa rugosa(Rosaceae) which have been used in a folkloric medicine for treating diabetics. The methanol extract was shown to lower the serum lipid level against the normal and 1% cholesterol and 0.5% cholic acid diet feeding to rats, respectively. When various fractions prepared from the above methanol extract was administered, the ethyl acetate-soluble fractions lowered the serum cholesterol level most remarkably. And when (+)-catechin from the ethyl acetate-soluble fractions was only administered to them, the serum cholesterol level was significantly lowered to 260$\pm$9.3mg/dl, the decrease of 17% for the control group. Therefore, it is suggested that (+)-catechin is one of the active principles of this plant.

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Effects of Youngkaechulgamtang on Hepatotoxicity (영계출감탕의 간독성에 미치는 영향)

  • Kim, Tae-Hee;Yang, Ki-Sook;Park, Seung-Ah
    • Korean Journal of Pharmacognosy
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    • v.30 no.1
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    • pp.12-17
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    • 1999
  • The youngkaechulgamtang (Y) composed of four herb drugs, including Hoelen (H). Cinnamomi Ramulus (C). Atractylodis Rhizoma Alba (A) and Glycyrrhizae Radix (G). In oriental medicine literatures, Youngkaechulgamtang is described to be effective in headache, inflammation, uremia, gastritis, diarrhea and hypertension. To estimate the clinical effectiveness of Youngkaechulgamtang, several pharmacological experiments were carried out. The results are summerized as follows; On acetaminophen-induced hepatotoxicity, C+A, Y-G, Y-H, MIX and Y showed the significant elevation of glutathione-S-transferase. But, C+A, Y-G, Y-H, MIX and Y showed the significant suppression of serum aminotransferases. On ANIT-induced cholestasis, U (Ursodesoxycholic acid 50 mg/kg)+$Y_l$ (760 mg/kg) showed the significant increase of bile juice volume. $Y_l,\;Y_2$ (1520 mg/kg), U, $U+Y_l$ showed the remarkable increase of cholic acid. U and $U+Y_l$ showed the significant decrease of total bilirubin. From these results, it is suggest that Y shows liver protective effect against various hepatic injury. Especially, Youngkaechulgamtang was more effective than mixture of 4 ingredients in the elevation of glutathione-S-transferase in acetaminophen-induced hepatotoxicity.

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Fructooligosaccharides Alter Profiles of Fecal Short-Chain Fatty Acids and Bile Acids in Rats

  • Sung, Hye-Young;Choi, Young-Sun;Cho, Sung-Hee;Yun, Jong-Won
    • Food Science and Biotechnology
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    • v.15 no.1
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    • pp.51-56
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    • 2006
  • We investigated the effects of fructooligosaccharides and chicory inulin on the profiles of cecal and fecal short-chain fatty acids (SCFAs) and fecal bile acids in rats. Thirty-six Sprague Dawley male rats weighing about 190 g were randomly divided among four treatments; control diet, control diet +6%(w/w) fructooligosaccharide (POS), control diet +6% chicory inulin oligosaccharide(CIOS), and control diet +6% chicory inulin(CI). The rats were pair-fed and experimental diets were maintained for 5 weeks. Cecal and fecal pH was significantly decreased in rats that were fed fructooligosaccharides and chicory inulin. Cecal propionate was significantly elevated in rats fed CIOS diets, and butyrate was lower in rats fed FOS and CI than control values. Cecal lactate was significantly higher in the FOS group than in the control group. The fecal excretions of acetate and total SCFA were 200-300% higher in rats that were fed fructooligosaccharides and chicory inulin than in the control group. Lactate excretion was highest in rats that were fed FOS, followed by those fed CIOS and CI. The cholic acid and total bile acid concentrations in feces were significantly lower in the rats that were fed fructooligosaccharides and chicory inulin. The deoxycholic acid concentrations in wet feces were significantly lower in the groups of rats that ate CIOS (0.186 mM), FOS (0.274 mM), and CI (0.362 mM) than in the control group (0.595 mM). Among the fructans, short-chain fructooligosaccharide was more effective at decreasing colonic pH and lactate production, but medium-chain chicory inulin oligosaccharide was more effective at increasing fecal butyrate and lowering the fecal secondary bile acid concentration.