OBJECTIVETo investigate the effects of treatment with ursodeoxycholic acid (UDCA) on intrahepatic cholestasis in rats, and to explore its mechanism.

METHODRats suffering from intrahepatic cholestasis were treated with UDCA. Their serum alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin (TBIL), direct bilirubin (DBIL), gamma-glutamyl transpeptidase (gamma-GT), total cholesterol (TCH), bile flow, total bile acid excretion, total Na(+) and TCH of bile were measured before and after treatment. In addition, the changes of liver tissue under microscrope were observed and recorded.

RESULTSCompared with the control group, serum ALT, ALP, TBIL, DBIL, gamma-GT and TCH of rats in the treatment group decreased, while bile flow, total bile acid excretion, total Na(+) and TCH decreased significantly. Degeneration of hepatocytes, infiltration of inflamed cells and proliferation of small bile ducts in the treatment group were improved under microscope.

CONCLUSIONUDCA may have therapeutic effects on cholestatic hepatitis. The mechanism may involve in its hydrophilicity, choleretic effect and immune modulation.

Animals ; Cholestasis, Intrahepatic ; drug therapy ; Male ; Rats ; Rats, Sprague-Dawley ; Ursodeoxycholic Acid ; therapeutic use

Animals ; Cholestasis, Intrahepatic ; drug therapy ; Male ; Rats ; Rats, Sprague-Dawley ; Ursodeoxycholic Acid ; therapeutic use

A chronic cholestasis model was induced in mice by feeding a diet containing 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine(DDC). The effects of Ershiwuwei Songshi Pills(ESP) on endogenous metabolites in mice with chronic cholestasis were investigated by metabolomics analysis based on liquid chromatography-mass spectrometry(LC-MS). The results showed that ESP was effective in improving pathological injury and reducing serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP), and total bile acid in the model mice. Meanwhile, 13 common differential metabolites were revealed in metabolomic screening between the model/control group and the model/ESP group, including uric acid, glycolaldehyde, kynurenine, flavin adenine dinucleotide, L-3-phenyllactic acid, I-urobilin, leukotriene D4(LTD4), taurocholic acid, trioxilin A3, D-inositol-1,4-diphosphate, PC [16:0/20:2(11Z,14Z)], PC[14:0/22:2(13Z,16Z)], and PC[20:4(5Z,8Z,11Z,14Z)/20:4(5Z,8Z,11Z,14Z)]. After ESP intervention, the levels of all 13 differential metabolites were significantly retraced, and pathway analysis showed that ESP achieved its therapeutic effect mainly by affecting arachidonic acid metabolism, glycerophospholipid metabolism, tryptophan metabolism, and primary bile acid biosynthesis. This study elucidated the mechanism of action of ESP against chronic cholestasis based on metabolites.
Animals ; Bile Acids and Salts ; Cholestasis/drug therapy* ; Chromatography, Liquid ; Medicine, Tibetan Traditional ; Metabolomics ; Mice

OBJECTIVETo observe the clinical efficacy of comprehensive Western medical treatment plus Compound Yindan Decoction (CYD) in treatment of acute cholestatic hepatitis (ACH).

METHODSUsing randomized controlled study, 60 ACH patients in line with inclusive criteria were randomly assigned to the treatment group (treated by comprehensive Western medical treatment plus CYD) and the control group (treated by comprehensive Western medical treatment alone), 30 in each group. Scores for symptoms and levels of liver functions [total bilirubin (TBIL), direct bilirubin (DBIL), alkaline phosphatase (ALP), glutamyl transpeptidase (GGT), total biliary acid (TBA)] were observed before and after treatment.

RESULTSCompared with before treatment in the same group, total scores for symptoms decreased in the treatment group and the control group at the end of the 1st and the 4th week after treatment (all P < 0.05). Compared with the control group, total scores for symptoms decreased in the treatment group at the end of the 1st week (P < 0.05). Compared with before treatment, serum levels of TBIL, DBIL, ALP, GGT, and TBA all decreased in the two groups at the end of the 4th week after treat- ment (P < 0.01). Compared with the control group, serum levels of TBIL, DBIL, ALP, GGT, and TBA all decreased in the treatment group at the end of the 1st and the 2nd week after treatment (P < 0.05). Compared with the control group, the average time for TBIL and DBIL decreasing to the level less than five times the normal value was significantly shorter in the treatment group (P < 0.05).

CONCLUSIONCYD could significantly improve clinical symptoms of ACH patients, decrease serum levels of TBIL and DBIL, reduce serum levels of ALP, GGT, and TBA, obviously improve cholestasis, and promote the recovery.

Alkaline Phosphatase ; Bilirubin ; Cholestasis ; Combined Modality Therapy ; Drugs, Chinese Herbal ; therapeutic use ; Hepatitis ; drug therapy ; Humans ; gamma-Glutamyltransferase

OBJECTIVETo observe the clinical effects of Linda Mixture (LM) on cholestatic liver diseases caused by cytomegalovirus (CMV) infection.

METHODSTotally 240 CMV infected cholestatic liver diseases infants, who were hospitalized at the Department of Integrated Traditional Chinese and Western Medicine, Wuhan Children's Hospital from January 2008 to June 2011, were randomly assigned to the treatment group (120 cases) and the control group (120 cases). Patients in the treatment group were treated by LM combined ganciclovir, while those in the control group were treated by ganciclovir alone. The therapeutic course was 2 months. The patients were assigned to 3 sub-groups according to the quantification standards of symptoms and signs, i. e., the No. 1 treatment group (mild, 30 cases), the No. 1 control group (mild, 30 cases), the No. 2 treatment group (moderate, 30 cases), the No. 2 control group (moderate, 30 cases), the No. 3 treatment group (severe, 30 cases), the No. 1 control group (severe, 30 cases). The clinically cured rate and the total effective rate, the jaundice subside time, the retraction time for Gan and Pi, the body weight growth, the indices of the liver function, and lab indices of CMV infection were observed before and after treatment.

RESULTSAfter treatment the cured rate was 77.50% and the total effective rate was 88.33% in the treatment group, while they were 60.83% and 76.67% in the control group. There was statistical difference between the two group (P<0.05, P<0.01). There was some improvement in the jaundice subside time, the retraction time for Gan and Pi, the body weight growth, the indices of the liver function in the two groups. Better results were obtained in the treatment group than in the control group, showing statistical difference (P<0.05, P<0.01). The lab indices of CMV infection showed negative to some degrees. The negative rates of serum IgM (83.54% in the treatment group and 63. 64% in the control group) and the serum CMVDNA (84.52% in the treatment group and 67.47% in the control group) were better in the treatment group than in the control group, showing statistical difference (P<0.01). There was no obvious difference in the negative rate of CMV antigen in urine between the two groups (P>0.05).

CONCLUSIONSLM combined ganciclovir therapy showed definite effects in treating cholestatic liver diseases caused by CMV infection. Early treatment for severe infants might change their prognosis. LM also could alleviate adverse reactions during the therapeutic course.

Cholestasis ; complications ; drug therapy ; virology ; Cytomegalovirus Infections ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Ganciclovir ; therapeutic use ; Humans ; Infant ; Liver Diseases ; drug therapy ; etiology ; virology ; Male ; Phytotherapy

Clinical variants of hepatitis A include the prolonged, relapsing and cholestatic forms. Here, the first childhood case of hepatitis A, with a combination of the relapsing and cholestatic forms is presented, a 14-year old boy. In the first phase of the illness, while the AST and ALT levels were declined, th total and direct bilirubin and GGT were increased. The patient was thought to have the cholestatic form of hepatitis A. Du to intense pruritus and high bilirunbin levels, ursodeoxycholic acid (UDCA) therapy was started. On the 17th day, the decreased AST and ALT levels began to increase, reaching levels as high as 484 U/L and 862 U/L, respectively. The UDCA treatment was stopped on the 64th day. On the 164th day, all his laboratory parameters were within normal limits, but the anti-HAV IgM was still positive.
Adolescent ; Alanine Transaminase/blood ; Aspartate Aminotransferases/blood ; Cholestasis/classification/drug therapy/*etiology ; Hepatitis A/*complications ; Human ; Male ; Ursodeoxycholic Acid/therapeutic use

To screen the active ingredients of Gardenia jasminoides and potential targets,and investigate the mechanisms against cholestasis based on network pharmacology technology. Twenty-one active components of G. jasminoides were retrieved and the target sites were screened by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform( TCMSP). Cytoscape3. 2. 1 was used to construct the component-target network. Two hundred and eight targets related to cholestasis were searched and screened through Dis Ge NET,KEGG and OMIM databases. The key targets of G. jasminoides components and cholestasis were integrated and screened,and the component-target-disease network was constructed with Cytoscape 3. 2. 1 software to screen out the core network whose freedom degree was greater than the average value. The Clue GO plug-in of Cytoscape 3. 2. 1 software was used to analyze the biological processes and pathway enrichment of G. jasminoides in regulation of cholestasis. GO biological process analysis revealed 17 biological processes,involving 3 signaling biological processes related to cholestasis,i.e. acute inflammatory response,positive regulation of reactive oxygen species metabolic process,and nitric oxide biosynthetic process. KEGG-KEEG-305 terms and REACTOME pathways analysis revealed 17 regulatory pathways,involving 4 signaling pathways related to cholestasis,i.e. metabolism of xenobiotics by cytochrome P450,nuclear receptor transcription pathway,GPVI-mediated activation cascade and platelet activation. It was found that aqueous extract of G. jasminoides could improve serum biochemical abnormalities in ANIT-induced cholestasis rats. Aqueous extract of G. jasminoides could decrease the protein and mRNA expression levels of ESR1 in liver tissues,and increase the protein and mRNA expression levels of PPARG,NOS2,F2 R,NOS3,and NR3 C1. To sum up,the possible mechanisms of G. jasminoides against cholestasis may be related with the above three processes and four pathways.
Animals ; Cholestasis ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; Gardenia ; chemistry ; Medicine, Chinese Traditional ; Plant Extracts ; pharmacology ; Rats ; Signal Transduction

Chrysosplenium nudicaule,Tibetan name " Yajima",is recorded as an effective medicine for the treatment of liver and gallbladder diseases by Tibetan Pharmacopoeia published in the past dynasties,but its traditional efficacy has not yet been investigated by means of modern pharmacological research methods. In this paper,the protective effect of extract of C. nudicaule(ECN) on liver injury in mice was observed by using the mice model of intrahepatic cholestasis(IC) induced by α-naphthyl isothiocyanate(ANIT) and the possible mechanism by which ECN work as the therapeutic agent was discussed. The results showed that the serum levels of AST,ALT,ALP,DBIL,TBIL and TBA of the model mice were notably reduced in dose-dependent manner(P<0. 01,P<0. 05). The activity of SOD and GSH-Px in the liver homogenate of mice was increased,while the content of MDA was decreased(P<0. 01,P<0. 05).Pathological examination of liver in mice showed that ECN could improve the pathological changes of liver tissue in mice. The mRNA expression level of genes related to bile acid metabolism were detected by RT-PCR and the results suggested that ECN could significantly increase the expression of genes such as BSEP,FXR and MRP2(P<0. 01,P<0. 05),meanwhile significantly reduce the expression of CYP7 A1(P<0. 01,P<0. 05). These results confirmed the protective effect of ECN on intrahepatic cholestasis-induced liver injury in mice,and indicated that the mechanism may be related to activating FXR and its target genes,reducing bile acid synthesis and increasing bile acid excretion. This study provides a modern pharmacological basis for the clinical application of Yajima in Tibetan medicine.
Animals ; Cholestasis, Intrahepatic ; chemically induced ; drug therapy ; Liver ; Medicine, Tibetan Traditional ; Mice ; Plant Preparations ; pharmacology ; Saxifragaceae ; chemistry

OBJECTIVETo study the therapeutic effect of glucocorticoid on early postoperative cholangiole cholestasis hyperbilirubinemia after liver transplantation.

METHODSThirteen liver transplantation recipients with serum total bilirubin above 171 micromol/L at two weeks to one month postoperatively were enrolled in this study. After exclusion of liver blood supply anomalies, bile duct complications, and acute rejection and establishment of a pathological diagnosis of cholangiole cholestasis by hepatic biopsy, hydrocortisone sodium succinate was infused. The liver functions of the patients were tested at 1 day before and 1 day and 1 week after the treatment. Hepatic biopsy was performed before and 1 week after the treatment to observe histopathological changes.

RESULTSThe serum levels of total bilirubin decreased significantly after the treatment with glucocorticoid. Pathology of the hepatic biopsy demonstrated the resolution of cholangiole cholestasis 1 week after the treatment.

CONCLUSIONGlucocorticoid treatment is effective for early postoperative cholangiole cholestasis hyperbilirubinemia after liver transplantation.

Adult ; Aged ; Cholestasis, Intrahepatic ; complications ; Female ; Humans ; Hydrocortisone ; analogs & derivatives ; therapeutic use ; Hyperbilirubinemia ; drug therapy ; etiology ; Liver Transplantation ; Male ; Middle Aged ; Postoperative Complications ; drug therapy

OBJECTIVETo evaluate the therapeutic effect of Yinchenghao decoction (YCHD) and S-adenosy-L-methionine (SAM) in treating intrahepatic cholestasis of pregnancy (ICP) and improving prognosis of perinatal newborn babies.

METHODSSixty in-patients of ICP were randomly divided into two groups, the group A treated with YCHD and the group B treated with SAM. The symptom of itching and serum biochemical indexes, including glycocholic acid, bilirubin and transaminase, were observed after 3 weeks treatment, and the prognosis of perinatal newborn babies between the two groups was compared after delivery.

RESULTSAfter treatment, the symptom of itching, serum levels of glycocholic acid, bilirubin and transaminase improved significantly (P < 0.05) in both groups, and the prognosis of newborn in the two groups was similar (P > 0.05).

CONCLUSIONBoth YCHD and SAM could effectively treat ICP. The former is rather cheaper, so it is more feasible for spreading.

Adult ; Cholestasis, Intrahepatic ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Phytotherapy ; Pregnancy ; Pregnancy Complications ; drug therapy ; Pregnancy Outcome ; S-Adenosylmethionine ; therapeutic use