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

• Biomolecules & Therapeutics
• /
• 제27권2호
• /
• pp.134-144
• /
• 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.

• Journal of Nutrition and Health
• /
• 제55권1호
• /
• pp.36-46
• /
• 2022

Quercetin의 지질대사 개선 효과에 대한 작용기전을 확인하기 위해 C57BL/6J mouse를 사용하여 실험을 수행하였다. 고콜레스테롤혈증을 유도하기 위해 6주간 1% 콜레스테롤과 0.5% cholic acid를 함유하는 고콜레스테롤 식이를 급여하였으며, quercetin은 0.05%와 0.1%의 수준으로 고콜레스테롤 식이에 추가하여 같은 기간 동안 제공하였다. Quercetin은 혈청과 간의 중성지방 및 콜레스테롤 수준을 용량 의존적으로 감소하는 것으로 나타났다. 고콜레스테롤 식이를 섭취한 쥐의 간에서 지방 합성을 촉진하는 SREBP-1c, ACC1 및 FAS 유전자 발현이 quercetin 섭취에 의해 억제되는 것을 확인하였다. Quercetin은 간세포 내에서 에너지 대사를 조절하는 AMPK 활성을 증가시켰다. 이에 반해 암세포 증식을 촉진하고 지방간에서 높게 발현되는 miR-21 발현은 quercetin 섭취에 의해 감소되었다. 본 연구의 결과는 quercetin이 고콜레스테롤 식이 섭취 쥐에서 혈청과 간의 지질 수준을 낮추는 지질대사 개선 효과가 있으며, 이러한 효과의 일부는 간 내 지방합성 유전자 (SREBP-1c, ACC1 및 FAS) 발현, AMPK 활성 및 miR-21 조절을 통해 매개된다는 것을 시사한다.

• Journal of Nutrition and Health
• /
• 제33권8호
• /
• pp.802-812
• /
• 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)

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 1996년도 춘계학술대회
• /
• pp.245-245
• /
• 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.

• 한국독성학회:학술대회논문집
• /
• 한국독성학회 2001년도 International Symposium on Signal transduction in Toxicology
• /
• pp.142-142
• /
• 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)

• Journal of Pharmaceutical Investigation
• /
• 제16권4호
• /
• pp.148-151
• /
• 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.

• 약학회지
• /
• 제31권6호
• /
• pp.394-398
• /
• 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.

• 생약학회지
• /
• 제30권1호
• /
• pp.12-17
• /
• 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.

• Food Science and Biotechnology
• /
• 제15권1호
• /
• pp.51-56
• /
• 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.