Bile ; Cholestasis ; etiology ; metabolism ; Humans

Bile ; metabolism ; Cholestasis ; metabolism ; pathology ; Humans

Animal medicine is an important part of traditional Chinese medicine(TCM). Bear bile is one of the rare animal-derived medicinal materials with the functions of clearing the liver, promoting bile secretion, calming the liver, relieving convulsions, clearing heat, and removing toxins. From the Jin Dynasty to the Tang Dynasty, bear bile was mainly used to treat internal diseases, surgical diseases, and pediatric diseases with limitations. At present, bear bile has been used to treat various diseases in pediatrics, gynecology, internal medicine, and surgery. Studies on the chemical constituents and pharmacological effects of bear bile mostly focused on bile acids. Although the non-bile acids also showed certain pharmacological effects, their mechanism of action was less investigated. At present, the source animals of bear bile are national second-class protected animals. Obtaining transformed bear bile powder through biotransformation is expected to alleviate the shortage of bear bile resources to a certain extent. Although related research on bear bile substitutes has protected bear bile resources, there are problems in functional quantification and modern interpretation. It is necessary to sort out the functions and indications of bear bile recorded in ancient books according to related modern research. This study firstly reviewed the evolution of bear bile functions and indications, analyzed the chemical components of bear bile, sorted out the relevant records of the efficacy and clinical application of bear bile in ancient books, and summarized the research progress in the safety of bear bile based on the modern pharmacological effects and clinical applications of bear bile, which is conducive to the clarification of modern efficacy and functional quantification of bear bile and the tentative exploration of the modern interpretation of bear bile.
Animals ; Bile/metabolism* ; Bile Acids and Salts ; Humans ; Medicine, Chinese Traditional ; Powders ; Ursidae/metabolism*

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

In this paper, a detailed analysis was made on relevant literatures about bear bile powder in terms of chemical component, pharmacological effect and clinical efficacy, indicating bear bile powder's significant pharmacological effects and clinical application in treating various diseases. Due to the complex composition, bear bile powder is relatively toxic. Therefore, efforts shall be made to study bear bile powder's pharmacological effects, clinical application, chemical composition and toxic side-effects, with the aim to provide a scientific basis for widespread reasonable clinical application of bear bile powder.
Animals ; Bile ; chemistry ; metabolism ; Bile Acids and Salts ; chemistry ; pharmacology ; Humans ; Medicine, Chinese Traditional ; Powders ; chemistry ; metabolism ; pharmacology ; Ursidae ; metabolism

OBJECTIVETo study the correlation between clinicopathological features and serum carbohydrate antigen 19-9 (CA19-9)/carcinoembryonic antigen (CEA) in patients with extrahepatic cholangiocarcinoma (ECC).

METHODSThe clinicopathological data of 126 cases of extrahepatic cholangiocarcinoma treated in our department from Jan. 1999 to Dec. 2012 were collected and analyzed in this study. The correlation between clinicopathological features and sensitivity of CA19-9/CEA was analyzed by chi-square test. The correlation of clinicopathological features and value of serum CA19-9/CEA was analyzed by t test and F test.

RESULTSThe average value of CA19-9 before surgery in the 126 patients was 595.3 U/ml. The values of CA19-9 in 91 patients were abnormal and the sensitivity of CA19-9 was 72.2%. The average value of CEA before surgery was 12.6 U/ml. The value of CEA in 26 patients were abnormal and the sensitivity of CEA was 20.6%. The values of combined detection of serum CA19-9 and CEA before surgery were abnormal in a total of 97 cases with a sensitivity of 77.0%. There was no significant correlation between clinicopathological features and sensitivity of CA19-9 (P > 0.05). The location of tumor was significantly correlated to the diagnostic sensitivity of CEA. The sensitivity of CEA to distal ECC was only 15.4%. The value of CA19-9 was relatively high in patients >60-year old or with neural invasion, while CEA was higher when tumor was located in the middle of bile duct (P < 0.05). There was no significant difference of serum CA19-9 before and after jaundice reduction (P > 0.05).

CONCLUSIONSThe diagnostic sensitivity of CA19-9 is not affected by gender, age, blood type, tumor location, degree of differentiation, tumor size, T stage, vascular tumor thrombus, lymph node metastasis, perineural invasion, and preoperative jaundice. However, the diagnostic sensitivity of CEA is affected by tumor location. The value of CA19-9 is correlated with tumor invasion and is relatively high in patients above 60 years old.

Bile Duct Neoplasms ; metabolism ; pathology ; Bile Ducts, Intrahepatic ; metabolism ; pathology ; Biomarkers, Tumor ; metabolism ; CA-19-9 Antigen ; metabolism ; Carcinoembryonic Antigen ; metabolism ; Cholangiocarcinoma ; metabolism ; pathology ; Humans ; Lymphatic Metastasis

OBJECTIVETo study the chemical constituents of bear bile.

METHODThe compounds were isolated by repeated column HP20 macroporous adsorption resin, Sephadex LH-20, ODS and silica gel as packing materials. The structures were identified on the basis of extensive spectroscopic data analysis and by comparison of their spectral data reported.

RESULTNine compounds were identified as 4',7-dihydroxyisoflavone (1), 4',7-dihydroxy-6-methoxyisoflavone (2), 4',6,7-trihydroxyisoflavone (3), 4'-methoxy-7-hydroxyisoflavone (4), tauroursodeoxycholic acid (5), taurochenodeoxycholic acid (6), ursodeoxycholic acid (7), chenodeoxycholic acid (8), cholesterol (9).

CONCLUSIONCompounds 1-4 were separated from bear bile for the first time.

Animals ; Bile ; chemistry ; Gallbladder ; chemistry ; Medicine, Chinese Traditional ; Ursidae ; metabolism

OBJECTIVETo research the effects of bile acids on the expression of interleukin-6 (IL-6) and the cell viability in QBC939 cell line.

METHODSHuman cholangiocarcinoma cells were stimulated with 800 µmol/L bile acid (CA), 100 µmol/L deoxycholate (DCA), 100 µmol/L chenodeoxycholic acid (CDCA), 1200 µmol/L gly acid (GCA), 200 µmol/L glycodeoxycholic acid (GDCA) and 300 µmol/L gly chenodeoxycholic acid (GCDCA).MTT assay and ELISA were used to detect the cell viability and the expression of IL-6 at 24 h, 48 h and 72 h.

RESULTSTreated by DCA, CDCA and GCDCA for 48 hours, the cell viability ratios changed to 0.61, 0.58 and 1.26, which were significant differences between control group and treated groups. And after 72 hours, the viability ratios of group CA, group DCA, group CDCA, group GCA, group GDCA and group GCDCA turned into 0.48, 0.50, 0.42, 1.29, 1.30 and 1.41. The differences of cell viability between bile acid-treated groups and control group were significant (P < 0.05). The expression of IL-6 in control group at 48 h and 72 h was (198 ± 32) ng/L and (323 ± 34) ng/L, while treated by CA, DCA, CDCA, GCA, GDCA and GCDCA respectively for 48 hours, the expression of IL-6 altered to (106 ± 33) ng/L, (88 ± 29) ng/L, (116 ± 54) ng/L, (413 ± 21) ng/L, (587 ± 32) ng/L and (366 ± 30) ng/L. After 72 hours, the expression of IL-6 of each bile acid-treated groups as above was (123 ± 66) ng/L, (45 ± 21) ng/L, (74 ± 45) ng/L, (792 ± 13) ng/L, (1310 ± 22) ng/L and (845 ± 18) ng/L, respectively. The differences between each bile acid-treated group and control group were significant (P < 0.05).

CONCLUSIONSFree bile acids (CA, DCA and CDCA) can inhibit the expression of IL-6 and the cell viability, while glycine conjugates (GCA, GDCA and GCDCA) can promote the expression of IL-6 and the cell viability. Bile acids can change tumor cell viability via IL-6 pathway.

Bile Acids and Salts ; pharmacology ; Bile Duct Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Cell Survival ; drug effects ; Humans ; Interleukin-6 ; metabolism

OBJECTIVETo investigate the change of bile composition and its role in bile duct injury after orthotopic liver transplantation (OLT).

METHODSRats were randomly divided into 3 groups: group A (sham surgery), group B (OLT with 1 h cold preservation), group C (OLT with 12 h cold preservation). The arterialized rat liver transplantation model with biliary extra-drainage was used in group B and C. Animals were sacrificed at posttransplant 1, 3, 5, 7, 10 and 14 day. Routine bile chemistry and pathological assays were performed.

RESULTSCold preservation/reperfusion injury (CPRI) could repress the secretion of bile salts and phospholipid. However, in contrast with a rapid increase of bile salt secretion, the biliary secretion of phospholipid recovered more slowly, leading to an abnormal high bile salts/phospholipid ratio early after transplantation. Further analysis suggested that the secretion of bile salts correlated strongly with biochemical and histopathological signs of bile duct injury.

CONCLUSIONSCPRI can lead to great changes of graft bile composition, which plays a role in the pathogenesis of bile duct injury following liver transplantation.

Animals ; Bile ; metabolism ; Bile Acids and Salts ; metabolism ; Bile Duct Diseases ; etiology ; Bile Ducts, Intrahepatic ; pathology ; Cold Ischemia ; Disease Models, Animal ; Liver Transplantation ; Male ; Postoperative Complications ; etiology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; complications ; metabolism ; pathology

OBJECTIVETo evaluate the pro-nucleating activity in 33.5 x 10(3) vesicular protein.

METHODSThe model biles were established according Kibe and Zhu. The pro-nucleating activity of 33.5 x 10(3) vesicular protein were examined by polarized light microscopy. The protein and its enzymatic deglycosylation and proteolysis fractions nucleation promoting activity were detected by cholesterol crystal growth assay.

RESULTS33.5 x 10(3) vesicular protein displayed apparent potency of pro-nucleation with activity of 0.310, and derived crystal growth curve indices It, Ig, Ic were presented as 0.57, 1.52, 1.63 respectively, but after treated by N-glycanase enzyme and pronase, no promoting activity were found.

CONCLUSIONThe 33.5 x 10(3) vesicular protein may be involved in the nucleation process of gallstone formation, which is regulated by its peptide and sugar chain.

Bile ; metabolism ; Cholelithiasis ; physiopathology ; Cholesterol ; metabolism ; Humans ; Macromolecular Substances ; Microscopy ; Models, Biological ; Protein Transport ; Proteins ; metabolism