Bile of animal(mainly chicken, pig, snake, cow, and bear) has long been used as medicine. As the major active components of bile, bile acids mainly include cholic acid, deoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid, and taurochenodeoxycholic acid. They interact with intestinal microorganisms in enterohepatic circulation, thereby playing an important part in nutrient absorption and allocation, metabolism regulation, and dynamic balance. Bile acids have pharmacological effects such as protecting liver, kidney, heart, brain, and nerves, promoting bile secretion, dissolving gallstones, anti-cancer, relieving cough and dyspnea, dispelling phlegm, treating eye diseases, and regulating intestinal function and blood glucose, which are widely used in clinical practice. This study summarized and analyzed the research on the chemical constituents and pharmacological effects of bile acids from medicinal animals, in a bid to provide scientific basis and reference for the further development and utilization of bile acids.
Animals ; Bile Acids and Salts ; Cattle ; Chenodeoxycholic Acid ; Cholic Acids ; Deoxycholic Acid ; Female ; Swine ; Ursodeoxycholic Acid

PURPOSE: Cytotoxicity of the bile acids on colon cancer cell lines was studied to know which bile acid was most cytotoxic to colonic mucosal epithelium. We performed agarose gel electrophoresis whether this toxicity was caused by detergent effect of the bile acids or by apoptotic pathway. MATERIALS AND METHODS: HT29, LoVo, SW620 colon cancer cell lines were exposed to lithocholate, cholate, deoxycholate and chenodeoxycholate with 50, 100, 150, 200, 250, 300 pM as final concentration in DMEM culture media for short time (for 2 hours) and for long time (for 5 days). Agarose gel electrophoresis was performed on each colon cancer cell lines (HT29, LoVo, SW620, SW480) after 1, 2, 3, 4, 5 days exposure to deoxycholate with 150 pM concentration to detect intemucleosomal fragmentation. RESULTS: There was no toxicity after short time exposure in all bile acids concentration and in all colon cancer cell lines. Of the bile acids, deoxycholate was most toxic for all colon cancer cell lines. And DNA fragmentation was noticed after 2 days exposure with deoxycholate. Only LoVo cell line showed apoptotic DNA pattern after 4 days of exposure with deoxycholate. CONCLUSION: Bile acids (especially deoxycholate) are suggested to be possible agents to cause apoptosis in colonic mucosal epithelium.
Apoptosis ; Bile Acids and Salts* ; Bile* ; Cell Line* ; Chenodeoxycholic Acid ; Cholates ; Colon* ; Colonic Neoplasms* ; Culture Media ; Deoxycholic Acid ; Detergents ; DNA ; DNA Fragmentation ; Electrophoresis, Agar Gel ; Epithelium ; Lithocholic Acid

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 ~ 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 X 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 ECl- 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.
Bile Acids and Salts ; Bile* ; Cholic Acid ; Colon ; Deoxycholic Acid ; Gastrointestinal Motility ; Ileum ; Muscle Cells ; Muscle Contraction ; Muscle, Smooth* ; Muscles ; Taurocholic Acid

Bile acids and synthetic its derivatives induced apoptosis in various kinds of cancer cells and had anticancer effects. However, it wasn`t discovered those materials have apoptosis induced effects on osteosarcoma cells. The present study was done to examine the synthetic bile acid derivatives induced apoptosis on osteosarcoma cells and such these apoptosis events. The synthetic bile acid derivatives, chenodeoxycholic acid (CDCA) induced the cell death on human osteosarcoma (HOS) cells contrary to ursodeoxycholic acid (UDCA). HS-1200, a synthetic derivative of CDCAs, was chosen to experiment apoptosis events in HOS cells. HOS cells treated with HS-1200 showed nucleus condensation, cytochrom c release, Bax/Bcl-xL alteration, activation of caspase-3 and caspase-activated deoxyribonuclease (CAD), and degradation of poly (ADP-ribose) polymerase (PARP). Though this study needs more investigations, these in vitro data suggest that treatment of the synthetic bile acid derivatives can give medical therapy on HOS cells.
Apoptosis* ; Bile Acids and Salts ; Bile* ; Caspase 3 ; Cell Death ; Chenodeoxycholic Acid ; Humans* ; Osteosarcoma* ; Ursodeoxycholic Acid

Metabolic profile of bile acids was used to evaluate hepatotoxicity of mice caused by ethanol extraction of Dioscorea bulbifera L. (ethanol extraction, ET) and diosbulbin B (DB), separately. Ultra-performance liquid chromatography coupled with quadrupole mass spectrometry (UPLC-MS) was applied to determine the contents of all kinds of endogenous bile acids including free bile acids, taurine conjugates and glycine conjugates. Obvious liver injuries could be observed in mice after administrated with ET and DB. Based on the analysis using principle components analysis (PCA), toxic groups could be distinguished from their control groups, which suggested that the variance of the contents of bile acids could evaluate hepatotoxicity caused by ET and DB. Meanwhile, ET and DB toxic groups were classified in the same trends comparing to control groups in the loading plot, and difference between the two toxic groups could also be observed. DB proved to be one of the toxic components in Dioscorea bulbifera L. Bile acids of tauroursodeoxycholic acid (TUDCA), taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA), taurodeoxycholic acid (TDCA), cholic acid (CA) and others proved to be important corresponds to ET and DB induced liver injury according to analysis of partial least square-discriminant analysis (PLS-DA) and the statistical analysis showed that there were significant differences between the control groups and toxic groups (P < 0.01). Furthermore, good correlation could be revealed between the foregoing bile acids and ALT, AST. It indicated that taurine conjugated bile acids as TUDCA, TCDCA, TCA and TDCA along with CA could be considered as sensitive biomarkers of ET and DB induced liver injury. This work can provide the base for the further research on the evaluation and mechanism of hepatotoxicity caused by Dioscorea bulbifera L.
Animals ; Bile Acids and Salts ; metabolism ; Chemical and Drug Induced Liver Injury ; metabolism ; Cholic Acid ; metabolism ; Chromatography, High Pressure Liquid ; methods ; Dioscorea ; toxicity ; Drugs, Chinese Herbal ; isolation & purification ; toxicity ; Heterocyclic Compounds, 4 or More Rings ; isolation & purification ; toxicity ; Least-Squares Analysis ; Male ; Mice ; Mice, Inbred ICR ; Plants, Medicinal ; toxicity ; Principal Component Analysis ; Rhizome ; toxicity ; Tandem Mass Spectrometry ; methods ; Taurochenodeoxycholic Acid ; metabolism ; Taurocholic Acid ; metabolism ; Taurodeoxycholic Acid ; metabolism

OBJECTIVETo provide evidence for three-level prevention of cholelithiasis by means of observing the effects of some choleretics on bile compositions drained from patients with pigment gallstone.

METHODSTwenty-seven patients suffering from primary pigment gallstones and having received treatment of choledochostomies plus T-tube or endoscopic nasal bile drainage (ENBD) were divided equally into three groups, and administered respectively with Lidanling (the LDL group), ursodesoxycholic acid (the UDA group) and combination of LDL and UDA (the LDL + UDA group) through oral intake (7 patients in each group). Besides, 6 post-operational patients got no treatment with any drug were allocated in the control group. Bile of all the patients was collected before treatment and on the 1, 3, 5, 7 th day after the treatment started to detect levels of total bile acid (TBA), glycocholic acid (GCA), taurocholic acid (TCA), glycocholic cheno-desoxycholic acid (GCDCA), total bilirubin (TBIL), uncombined bilirubin (UCB), concentration of calcium ion (Ca(2+)) as well as the bacterio-genetic and endogenous beta-glucuronidase activity for comparing.

RESULTSLevels of TBA, GCA, TCA and GCDCA got gradually increased in the UDA group and the LDL + UDA group after treatment (P < 0.05), while those in the LDL group remained unchanged, showing an insignificant difference as compared with those in the control group. In the LDL group and the LDL + UDA group, TBIL gradually increased while UCB gradually decreased in the course of treatment (P < 0.05). Moreover, levels of Ca(2+) and endogenous beta-glucuronidase activity got significantly lowered (P < 0.05).

CONCLUSIONCombined use of LDL and UDA could elevate levels of TBA, GCA, TCA, GCDCA, enhance the excretion of TBIL in patients with pigment gallstone after bile drainage, lower levels of UCB and Ca(2+) and the activity of endogenous beta-glucuronidase in the bile, so as to reduce the possibility of stone formation of bile, and therefore, it could be used to prevent the production of pigment gallstone, especially to prevent post-operative recurrence of stones.

Adult ; Bile ; chemistry ; Bile Acids and Salts ; analysis ; Bilirubin ; analysis ; Calcium ; analysis ; Cholagogues and Choleretics ; pharmacology ; Choledochostomy ; Cysteic Acid ; analogs & derivatives ; pharmacology ; Drainage ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Gallstones ; metabolism ; Glucuronidase ; analysis ; Glycocholic Acid ; analysis ; Humans ; Male ; Middle Aged ; Taurocholic Acid ; analysis ; Ursodeoxycholic Acid ; analogs & derivatives ; pharmacology

We studied the effects of bile acids on the induction of apoptosis 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 Ca2+ 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 A23187 induced DNA fragmentation. These results suggest that UDCA and LCA induce apoptosis in the HepG2 cells and that the activation of intracellular Ca2+ signals may play an important role in the apoptosis induced by these bile acids.
Apoptosis* ; Bile Acids and Salts* ; Bile* ; Calcimycin ; Calcium ; Carcinoma, Hepatocellular* ; Cell Death ; Cell Survival ; Cycloheximide ; DNA Fragmentation ; Hep G2 Cells ; Humans* ; Lithocholic Acid ; Ursodeoxycholic Acid

PURPOSE: Gastric stump cancer is defined as a cancer that develops in the stomach after a resection in cases of non-malignant or malignant gastric disease. The interval between the gastrectomy and the detection of gastric stump cancer must be over 5 years. Since duodenogastric reflux gastritis is a precancerous condition and one of the most important factors inducing gastric stump cancer, we compared the bile-acid content of gastric juice between gastric stump cancer patients and controls. MATENRIALS AND METHODS: To evaluate retrospectively the surgical treatment of patients with gastric stump cancer, we reviewed the cases histories of 1016 stomach cancer patients who had been operated on at the Department of General Surgery, Kosin University Gospel Hospital, between 1995 and 1998. The gastric juice was collected during the operations on the gastric stump cancer patients by using a needle puncture of the fundus of the stomach and during the endoscopic examinations of the control subjects. The samples were analyzed for various bile acids (gas chromatography/mass spectrometry). RESULTS: The 6 gastric stump cancer cases accounted for 0.6% of all gastric cancer patients; 5 patients were first operated on for a peptic ulcer and the remaining one for an adenocarcinoma of the stomach. All of the cases were men. The reconstruction method after the initial gastrectomy was a Billroth II in all cases. The sites of the gastric stump cancer were the anastomotic sitein 2 patients, the upper body in 2, the fundus in 1 and the cardia in 1. The operative methods were 3 total gastrectomies, 2 subtotal gastrectomies with Roux en Y anastomosis, and 1 partial gastrectomy with lymph node dissection and had a curative intention in all patients. All of the patients were still surviving at the time of this report. The gastric juices of 4 gastric stump patients showed significantly higher contents of cholic acid (36.42microgram/ ml) compared to the gastric juices of 35 control subjects (12.82microgram/ml)(p< or =0.0001). Chenodeoxycholic acid and lithocholic acid were not significantly different. CONCLUSION: The gastric juice of gastric stump cancer patients contained a significantly higher cholic acid content. At the time of the initial gastrectomy, an operative method that prevents duodenogastric reflux may prevent or minimize the development of gastric stump cancer, and more aggressive surgical treatment may improve survival.
Adenocarcinoma ; Anastomosis, Roux-en-Y ; Bile Acids and Salts ; Cardia ; Chenodeoxycholic Acid ; Cholic Acid ; Duodenogastric Reflux ; Gastrectomy ; Gastric Juice ; Gastric Stump* ; Gastritis ; Gastroenterostomy ; Humans ; Intention ; Lithocholic Acid ; Lymph Node Excision ; Male ; Needles ; Peptic Ulcer ; Precancerous Conditions ; Punctures ; Retrospective Studies ; Stomach ; Stomach Diseases ; Stomach Neoplasms

BACKGROUND: Bacterial and Helicobacter gene were commonly detected in diseased human bile, although the meaning of the presence of Helicobacter in biliary tract is still unclear. The aim of this study was to evaluate the changes of bile acid composition in bacterial and Helicobacter infected bile, and to determine whether Helicobacter pylori might grow in human bile or not. METHODS: Thirty bile samples were obtained by percutaneous transhepatic biliary drainage or gallbladder puncture during cholecystectomy. According to the polymerase chain reaction analysis using bacterial 16S rRNA and Helicobacter genus specific 16S rRNA primers, 3 groups were divided; Group I; no presence of any bacterial DNA, Group II; positive bacterial DNA only, Group III; positive bacterial and Helicobacter DNA. Bile acid analysis for deoxycholic acid (DCA), chenodeoxycholic acid (CDCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) was performed by high performance liquid chromatography. And then Helicobacter pylori was tried to culture in broth mixed with human bile at a final bile concentration of 50%. RESULTS: The concentrations of DCA in group II and III were very low and significantly reduced compared to group I (p<0.01, respectively). The concentrations of LCA or UDCA were not shown any relationships between groups. Helicobacter pylori has grown actively in the broth mixed with human bile containing both of less than 0.1 gm/L of DCA and CDCA, compared to no growth in media mixed with human bile containing more than 3.0 gm/L of DCA and/or CDCA. CONCLUSION: DCA seems to have the strongest antibacterial effect. Helicobacter pylori is likely to grow in human bile containg very low concentrations of CDCA and DCA.
Bile* ; Biliary Tract Diseases* ; Biliary Tract* ; Chenodeoxycholic Acid ; Cholecystectomy ; Chromatography, Liquid ; Deoxycholic Acid ; DNA ; DNA, Bacterial ; Drainage ; Gallbladder ; Helicobacter Infections* ; Helicobacter pylori ; Helicobacter* ; Humans ; Lithocholic Acid ; Polymerase Chain Reaction ; Punctures ; Ursodeoxycholic Acid

The effects of cholic acid and eight related cholanic acid analogs on bile flow and biliary excretion of bile salts and cholesterol were studied in rabbits. Bile acids were infused intravenously in anesthetized rabbits. In all except hyodeoxycholic or lithocholic acid treated animals increases in bile flow were recorded within 10 minutes during infusion of bile acid-The increase in bile f1ow associated with an increase in bile salt level in bile after cholic acid infusion was observed, however, there were little changes in biliary, cholesterol levels. Bile salt level in bile was not associated with bile flow after chenodeoxycholic acid infusion but the cholesterol level in bile was significantly increased. Ursodeoxycholic acid similarly increased cholesterol but to a lesser extent. Keto-forms of chenodeoxycholic acid were without action. These results indicate that both cholic and chenodeoxycholic acids have the capacity to alter specific biliary excretion of bile components, the former on bile salts and the latter on cholesterol-a precursor of bile acids in bile.
Animal ; Bile/analysis ; Bile/secretion* ; Bile Acids and Salts/administration & dosage ; Bile Acids and Salts/metabolism ; Bile Acids and Salts/pharmacology* ; Bilirubin/analysis ; Cholesterol/analysis ; Cholesterol/metabolism* ; Cholic Acids/analogs & derivatives ; Cholic Acids/analysis ; Female ; Liver/metabolism ; Male ; Rabbits