1.Clinical analysis of 22 patients with primary biliary cirrhosis.
Dingkang YAO ; Weifen XIE ; Lei WANG
Chinese Journal of Hepatology 2002;10(5):344-345
OBJECTIVETo improve the diagnosis and management of primary biliary cirrhosis (PBC).
METHODSClinical data of 22 cases of PBC were reviewed including the clinical manifestation, laboratory test, and the response to therapy.
RESULTSThere were 20 female patients with an average of 50 years old in total of 22 PBC patients. The major symptoms were pruritus, fatigue, anorexia, and abdominal discomfort. The major signs included jaundice, hepatomegaly, splenmegaly, and ascites. Very high levels of serum alkaline phosphatase (ALP) and serum gamma glutamyl transpeptidase (GGT), hyperbilirubinemia and hypergammaglobulinemia were also detected in most of the patients. The aminotransferase level was only slightly elevated but the AST/ALT ratio was reversed. It took 8 months (ranging from 2 months to 5 years) to confirm the diagnosis after the clinical manifestation onset. Ursodeoxycholic acid could decrease the serum levels of ALP and bilirubin in 80% of the patients (12/15) and improve the symptom of pruritus and fatigue in 72.7% of the patients (11/15).
CONCLUSIONSPBC mainly affects middle-aged women and the main clinical manifestations are hepatosplenomegaly, jaundice, pruritus, and fatigue. Liver function test typically reveal a cholestatic pattern accompanied by hypergammagloblinemia and a positive antimitochondrial antibody (AMA) including M2 subtype (AMA-M2). Ursodeoxycholic acid could improve the abnormal liver function tests and clinical features in PBC patients
Alkaline Phosphatase ; Bilirubin ; Cholestasis ; Female ; Hepatomegaly ; Humans ; Liver Cirrhosis, Biliary ; metabolism ; physiopathology ; Liver Function Tests ; Male ; Middle Aged ; Ursodeoxycholic Acid
2.Therapeutic Effects of Different Animal Bile Powders on Lipid Metabolism Disorders and Their Composition Analysis.
Da-Xin CHEN ; Jian-Feng CHU ; Shan LIN ; Ling ZHANG ; Hong-Wei CHEN ; Zhi-Wei SUN ; Jian-Feng XU ; Qiao-Yan CAI ; Li-Li WANG ; Jun PENG
Chinese journal of integrative medicine 2022;28(10):918-923
OBJECTIVE:
To compare the therapeutic effect of different animal bile powders on lipid metabolism disorders induced by high-fat diet in rats, and analyze the bioactive components of each animal bile powder.
METHODS:
Sixty Sprague-Dawley rats were randomly divided into 6 groups (n=10): normal diet control group, high-fat diet model group, high-fat diet groups orally treated with bear, pig, cow and chicken bile powders, respectively. Serum biochemical markers from the abdominal aorta in each group were analyzed. Changes in the body weight and liver weight were recorded. Pathohistological changes in the livers were examined. High performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was used to determine the composition of bioactive components in each animal bile powder.
RESULTS:
Treatment with different types of animal bile powders had different inhibitory effects on high-fat diet-induced increase of body weight and/or liver weight in rats, most notably in bear and pig bile powders (P<0.05). High-fat diet induced lipid metabolism disorder in rats, which could be reversed by treatment with all kinds of bile powders. Bear bile and chicken bile showed the most potent therapeutic effect against lipid metabolism disorder. Cow and bear bile effectively alleviated high-fat diet induced liver enlargement and discoloration, hepatocyte swelling, infiltration of inflammatory cells and formation of lipid vacuoles. Bioactive component analysis revealed that there were significant differences in the relative content of taurocholic acid, taurodeoxycholic acid and ursodeoxycholic acid among different types of animal bile. Interestingly, a unique component with molecular weight of 496.2738 Da, whose function has not yet been reported, was identified only in bear bile powder.
CONCLUSIONS
Different animal bile powders had varying therapeutic effect against lipid metabolism disorders induced by high-fat diet, and bear bile powder demonstrated the most effective benefits. Bioactive compositions were different in different types of animal bile with a novel compound identified only in bear bile powder.
Animals
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Bile/metabolism*
;
Biomarkers/metabolism*
;
Body Weight
;
Cattle
;
Diet, High-Fat
;
Female
;
Lipid Metabolism
;
Lipid Metabolism Disorders/metabolism*
;
Lipids/analysis*
;
Liver/metabolism*
;
Powders
;
Rats
;
Rats, Sprague-Dawley
;
Swine
;
Taurodeoxycholic Acid/metabolism*
;
Ursidae/metabolism*
;
Ursodeoxycholic Acid/metabolism*
3.Treatment of early and mid-term primary biliary cirrhosis by Qingying Huoxue Decoction Combined ursodeoxycholic acid: a clinical observation.
De-Cai FU ; Zong HUA ; Yi-Guang LI ; Hang-Yuan WU ; Xiao-Ye GUO ; Jian-Zhong HUANG
Chinese Journal of Integrated Traditional and Western Medicine 2015;35(3):290-293
UNLABELLEDOBJECTIVE To observe the clinical efficacy by Qingying Huoxue Decoction (QHD) combined ursodeoxycholic acid (UDCA) in treating patients with early and mid-term primary biliary cirrhosis (PBC). METHODS Totally 78 patients were randomly assigned to the treatment group and the control group, 39 in each group. All patients received basic treatment and took UDCA (at the daily dose of 13-15 mg/kg). Patients in the treatment group took QHD, one dose per day. The treatment course for all was 6 weeks. Clinical efficacy, gamma-glutamyl transferase (γ-GGT), alkaline phospatase (ALP), TBIL, alanine aminotransferase (ALT), and aspartate transaminase (AST) were observed before and after treatment. RESULTS Totally 21 (53. 8%) patients obtained complete response in the treatment group, with statistical difference when compared with that of the control group (11 cases, 30. 8%). Levels of GGT, ALP, ALT, AST, and TBIL decreased in the two groups after treatment (P < 0.01). Levels of ALP, GGT, and TBIL were obviously lower in the treatment group than in the control group (P < 0.05).
CONCLUSIONSQHD combined UDCA in treating early and mid-term PBC patients was superior to the effect of using UDCA alone. It also could improve patients' liver function.
Alanine Transaminase ; metabolism ; Aspartate Aminotransferases ; metabolism ; Drug Combinations ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Liver Cirrhosis, Biliary ; drug therapy ; Ursodeoxycholic Acid ; therapeutic use ; gamma-Glutamyltransferase ; metabolism
4.Hepatobiliary transport of glutathione and its role in cholestasis.
Xue-ying ZHANG ; Jin YANG ; Xue-fen YIN ; Xiao-dong LIU ; Guang-ji WANG
Acta Pharmaceutica Sinica 2009;44(4):327-332
Glutathione is a tripeptide comprised by L-glutamate, L-cysteine, and glycine, that serves antioxygenation and deintoxication functions within the cell. Recent study has found that glutathione is the main driving force for bile salt-independent bile flow, impaired biliary excretion of glutathione can lead to cholestasis. This review focuses on hepatobiliary transport of glutathione and its role in cholestasis. Based on the evidence of choleretic effect of glutathione, enhancement of biliary excretion of glutathione may be a good strategy for prevention and treatment of cholestasis.
Animals
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Biological Transport
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Cholestasis
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chemically induced
;
metabolism
;
prevention & control
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Estrogens
;
adverse effects
;
Glutathione
;
metabolism
;
Humans
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Jaundice, Chronic Idiopathic
;
genetics
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Liver
;
metabolism
;
Multidrug Resistance-Associated Proteins
;
genetics
;
metabolism
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Mutation
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Phalloidine
;
adverse effects
;
Ursodeoxycholic Acid
;
therapeutic use
5.Synthesis and biological evaluation of nitrate-oleanolic acid hybrids as inhibitors of HepG2 cell apoptosis.
Li CHEN ; Juan SHANG ; Zhi-feng WANG ; Yi-hu ZHANG ; Ji-de TIAN
Acta Pharmaceutica Sinica 2010;45(12):1516-1522
To find novel antihepatitis drugs, a series of nitrate-oleanolic acid (OA) hybrids (10a, 10b, 11a-11e and 12a-12c) were designed and synthesized on the basis of previous studies using OA as lead compound, which is widely found in natural plants and liver-specific metabolism. In the present study, ten novel NO-releasing derivatives of OA were synthesized by connecting nitrate to the OA-3-OH through varying lengths of linkers containing antioxidants which were designed to increase the ability of these target compounds to scavenge free radicals. The structures of these objective compounds were determined by IR, MS, 1H NMR and elemental analysis. Their protective effects on anti-Fas mediated HepG2 cell apoptosis were in vitro evaluated by LDH assay. Compound 12a is the most potent inhibitor. Its effect on anti-Fas mediated HepG2 cell apoptosis and amount of NO-releasing in vitro are similar to those of positive control NCX-1000.
Antioxidants
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chemistry
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Apoptosis
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drug effects
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Hep G2 Cells
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Humans
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Nitrates
;
chemical synthesis
;
chemistry
;
pharmacology
;
Nitric Oxide
;
metabolism
;
Nitric Oxide Donors
;
chemistry
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Oleanolic Acid
;
chemical synthesis
;
chemistry
;
pharmacology
;
Structure-Activity Relationship
;
Ursodeoxycholic Acid
;
analogs & derivatives
;
pharmacology
6.Effects of ursodeoxycholic acid on mRNA expression of MDR3 and FXR in infants with cholestatic hepatitis.
Qing TANG ; Lin-Lin WANG ; Qing-Wen SHAN ; Xiang YUN ; Xiu-Qi CHEN ; Ya-Nan DENG
Chinese Journal of Contemporary Pediatrics 2013;15(9):756-758
OBJECTIVETo analyze the effects of ursodeoxycholic acid (UDCA) on the mRNA expression of multidrug resistance protein 3 (MDR3) and farnesoid X receptor (FXR) in infants with cholestatic hepatitis.
METHODSTwenty-eight infants who were diagnosed with cholestatic hepatitis between July 2008 and July 2010 were included in the study. These patients received treatment with UDCA. The mRNA expression levels of MDR3 and FXR were measured by real-time quantitative RT-PCR with SYBR Green I, before and after treatment with UDCA.
RESULTSAfter treatment with UDCA, the infants with cholestatic hepatitis had significantly decreased serum levels of total bilirubin, direct bilirubin, alanine aminotransferase, and gamma-glutamyltransferase (P<0.05) and significantly increased mRNA expression of MDR3 (P<0.05). No significant change in mRNA expression of FXR was observed, however (P>0.05).
CONCLUSIONSUDCA improves liver function indices in infants with cholestatic hepatitis, which may be related to up-regulated mRNA expression of MDR3.
ATP Binding Cassette Transporter, Sub-Family B ; genetics ; Cholestasis ; complications ; drug therapy ; metabolism ; Female ; Gene Expression Regulation ; Hepatitis ; drug therapy ; etiology ; metabolism ; Humans ; Infant ; Male ; RNA, Messenger ; analysis ; Receptors, Cytoplasmic and Nuclear ; genetics ; Ursodeoxycholic Acid ; pharmacology ; therapeutic use
7.Retrospective analysis of autoimmune hepatitis-primary biliary cirrhosis overlap syndrome in Korea: characteristics, treatments, and outcomes.
Yoonsang PARK ; Yuri CHO ; Eun Ju CHO ; Yoon Jun KIM
Clinical and Molecular Hepatology 2015;21(2):150-157
BACKGROUND/AIMS: Overlap syndrome of autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) (AIH-PBC overlap syndrome) is a rare disease that has not been clearly characterized in Korean patients. This study investigated the clinical features of AIH-PBC overlap syndrome compared with those of AIH and PBC alone. METHODS: This retrospective cohort study included 158 consecutive patients who were diagnosed as AIH (n=61), PBC (n=81), or AIH-PBC overlap syndrome (n=9) based on the Paris and the International Autoimmune Hepatitis Group (IAIHG) criteria from 2001 to 2011 in Korea. We compared the clinical features of these three groups retrospectively, including their biochemical characteristics, treatments, responses, and clinical outcomes. RESULTS: The AIH-PBC overlap syndrome patients exhibited biochemical characteristics of both AIH and PBC, and showed a similar response to ursodeoxycholic acid (UDCA) monotherapy as for the PBC patients. However, the response of AIH-PBC overlap syndrome patients to UDCA and steroid combination therapy was worse than the response of AIH patients to steroid-based therapy (P=0.024). Liver cirrhosis developed more rapidly in AIH-PBC overlap syndrome patients than in AIH patients group (P=0.013), but there was no difference between AIH-PBC overlap syndrome patients and PBC patients. The rates of developing hepatic decompensation did not differ significantly between the groups. CONCLUSIONS: The AIH-PBC overlap syndrome patients exhibited a worse response to UDCA and steroid combination therapy and a faster cirrhotic progression compared with AIH patients.
Adult
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Aged
;
Cohort Studies
;
Drug Therapy, Combination
;
Female
;
Hepatitis, Autoimmune/complications/*diagnosis
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Humans
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Liver/metabolism/pathology
;
Liver Cirrhosis, Biliary/complications/*diagnosis/drug therapy
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Male
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Middle Aged
;
Republic of Korea
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Retrospective Studies
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Steroids/therapeutic use
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Treatment Outcome
;
Ursodeoxycholic Acid/therapeutic use
8.Effects of choleretics on bile compositions drained from patients with pigment gallstone.
Bai-jun SUN ; Nai-qiang CUI ; Dong-hua LI ; Qian WANG
Chinese journal of integrative medicine 2006;12(2):101-106
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
9.Effect of ursodeoxycholic acid on TGF beta1/Smad signaling pathway in rat hepatic stellate cells.
Tie-jun LIANG ; Jun-hua YUAN ; Yan-rong TAN ; Wan-hua REN ; Guo-qing HAN ; Jie ZHANG ; Lai-cheng WANG ; Cheng-yong QIN
Chinese Medical Journal 2009;122(10):1209-1213
BACKGROUNDHepatic fibrosis is the key stage of the pathological progress from hepatic injury to cirrhosis. Ursodeoxycholic acid (UDCA) has been known as having significant clinical therapeutic effects on chronic liver diseases. Our research aimed to study the effect of UDCA on the signaling pathway of transforming growth factor beta1 (TGFbeta1)/Smad and discuss its possible molecular mechanisms of inhibiting hepatic fibrosis.
METHODSRat hepatic stellate cells were cultured in vitro and randomly assigned to 4 groups. Group A was control group, with only DMEM culture medium applied, and groups B, C, D were experimental groups, with different doses of UDCA (1.0 mmol/L, 0.5 mmol/L and 0.25 mmol/L respectively) added into their DMEM culture medium for further culture of 24 hours and 48 hours. The protein expressions of TGFbeta1, TGF type I receptor, Smad3, Smad4 and Smad7 were measured by Western blotting, as well as the expressions of TGFbeta1, Smad3, Smad7 and cAMP response element (CREB) binding protein (CBP) mRNA by real-time PCR. SPSS 11.5 statistical package was adopted for data analyses.
RESULTSCompared with control group, the mRNA expressions of TGFbeta1 in the high and middle UDCA dose groups for 24 hours and 48 hours significantly decreased (P < 0.05), the protein expressions of TGFbeta1 in the two above groups for 48 hours and in the high dose group for 24 hours significantly decreased (P < 0.05). The protein and mRNA expressions of Smad3 in each UDCA dose group for 24 hours and 48 hours significantly decreased, with significant difference among different UDCA dose groups and between that of 24 hours and 48 hours observed (P < 0.05). The protein and mRNA expressions of Smad7 in the high and middle UDCA dose groups for 24 hours and 48 hours significantly increased. The CBP mRNA expression in each UDCA dose group for 24 hours and 48 hours significantly decreased (P < 0.05), with significant difference among different UDCA dose groups observed (P < 0.05).
CONCLUSIONUDCA could curb the development of hepatic fibrosis through affecting the signaling pathway of TGFbeta1/Smad by inhibiting the expressions of TGFbeta1, Smad3 and CBP and increasing the expression of Smad7.
Animals ; Blotting, Western ; Cells, Cultured ; Cholagogues and Choleretics ; pharmacology ; Cyclic AMP Response Element-Binding Protein ; genetics ; Hepatic Stellate Cells ; drug effects ; metabolism ; Humans ; Polymerase Chain Reaction ; Rats ; Receptors, Transforming Growth Factor beta ; metabolism ; Signal Transduction ; drug effects ; Smad Proteins ; metabolism ; Smad3 Protein ; genetics ; metabolism ; Smad4 Protein ; metabolism ; Smad7 Protein ; metabolism ; Transforming Growth Factor beta1 ; metabolism ; Ursodeoxycholic Acid ; pharmacology
10.Targeting of nitric oxide-donor and related drugs.
Yi-Hua ZHANG ; Ji-De TIAN ; Si-Xun PENG
Acta Pharmaceutica Sinica 2006;41(6):481-486
Animals
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Apoptosis
;
drug effects
;
Azo Compounds
;
chemical synthesis
;
pharmacology
;
Cell Line, Tumor
;
Drug Delivery Systems
;
Humans
;
Liver
;
metabolism
;
Liver Neoplasms
;
pathology
;
Nitrates
;
chemical synthesis
;
pharmacology
;
Nitric Oxide Donors
;
chemical synthesis
;
pharmacology
;
Oleanolic Acid
;
analogs & derivatives
;
chemical synthesis
;
pharmacology
;
Piperazines
;
chemical synthesis
;
pharmacology
;
Ursodeoxycholic Acid
;
analogs & derivatives
;
chemical synthesis
;
pharmacology