curcumin and Cholestasis

Since 1900 bc, several therapeutic activities have been attributed to the rhizomes of the plant Curcuma longa for a variety of diseases, including liver disorders. Curcumin, the main active compound obtained from this plant, was first isolated two centuries ago and its structure as diferuloylmethane was determined in 1910. Curcumin has shown anti-inflammatory, anti-oxidant, antifungal, antibacterial and anticancer activities. The pharmacological properties of curcumin were reviewed recently and focused mainly on its anticancer properties. However, its beneficial activity on liver diseases (known centuries ago, and demonstrated recently utilizing animal models) has not being reviewed in depth until now. The curcumin ability to inhibit several factors like nuclear factor-kappaB, which modulates several pro-inflammatory and profibrotic cytokines as well as its anti-oxidant properties, provide a rational molecular basis to use it in hepatic disorders. Curcumin attenuates liver injury induced by ethanol, thioacetamide, iron overdose, cholestasis and acute, subchronic and chronic carbon tetrachloride (CCl(4)) intoxication; moreover, it reverses CCl(4) cirrhosis to some extent. Unfortunately, the number of studies of curcumin on liver diseases is still very low and investigations in this area must be encouraged because hepatic disorders constitute one of the main causes of worldwide mortality.

Topics: Animals; Carbon Tetrachloride; Cholestasis; Curcuma; Curcumin; Humans; Iron; Liver; Liver Cirrhosis; Liver Cirrhosis, Biliary; Liver Diseases; Thioacetamide

Right upper abdominal pain may often be caused by biliary dyskinesia. Choleretica and cholekinetica are widely used for medical treatment of complaints due to biliary dyskinesia despite of a lack of randomized clinical trials which may prove their efficacy and potency.. The present prospective multicenter pilot study analyzes the effects of Cholagogum F Nattermann (dried extracts from Schöllkraut and Curcuma) in comparison with placebo in patients with dumpy or colicky abdominal pain in the right upper quadrant due to biliary dyskinesia. Cholagogum was given in 39 patients and placebo in 37 patients for 3 weeks, respectively.. The reduction of dumpy and colicky pain was more rapid during the first treatment week in patients who received Cholagogum F when compared to those who received placebo. The reduction of other complaints (feeling of being filled up, food intolerance, nausea, vomiting, meteorism) (secondary variables) was similar in patients who received Cholagogum F versus placebo during the whole treatment period. The were no side-effects in patients who received Cholagogum.. The study presents the first solid indication that extracts from Schöllkraut/Curcuma (Cholagogum F Nattermann) which have widely been used in daily practice for many decades have beneficial effects on pain due to biliary dyskinesia.

Topics: Abdominal Pain; Adult; Cholagogues and Choleretics; Cholestasis; Curcumin; Double-Blind Method; Drug Combinations; Dyspepsia; Female; Humans; Male; Phytotherapy; Pilot Projects; Plant Extracts; Prospective Studies; Statistics, Nonparametric

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Bile Ducts; Cholestasis; Curcumin; Disease Models, Animal; Heme Oxygenase-1; Hepatitis, Chronic; Humans; Ligation; Lipid Metabolism; Liver; Male; Membrane Proteins; Mice; Protoporphyrins

To investigate the protective effects of curcumin on bile duct ligation(BDL)-induced liver cholestasis in mice, so as to provide a new treatment strategy for liver fibrosis.. Forty-two healthy adult male BALB/c mice were randomly divided into sham group (n =6), sham+curcumin group (n=6), BDL treatment group (n=10), BDL+curcumin group(n=10), BDL+curcumin+ZnPP group (n=10). Seven days after BDL operation, the sham operation + curcumin group and the BDL+ curcumin group were treated with curcumin at the dose of 30 mg/kg by intraperitoneal injection once a day for 7 days.The mice in BDL+ curcumin +ZnPP group were treated with curcumin (30 mg/kg) and ZnPP (50 μmol/kg) by intraperitoneal injection once a day for 7 days. For the sham group and the BDL group, mice were treated with equal-volume saline daily by intraperitoneal injection. After 14 days of BDL, the plasma and liver tissues were collected, the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. The pathological changes of liver tissue and liver fibrosis were observed, and the protein expression of HO-1 in liver tissue was detected.. Compared with the sham group, mice in the BDL group had enlarged liver gallbladder and the serum levels of ALT and AST were increased significantly (P＜0.05). Meanwhile, the results of Sirius red staining and qRT-PCR of pro-fibrosis related genes showed collagen deposition in the liver, and immunohistochemistry of macrophages and neutrophils showed inflammatory cell infiltration in the liver. Compared with the BDL group, the serum levels of ALT and AST in the curcumin treatment group were decreased significantly (P＜0.05), collagen deposition and inflammatory cell infiltration were improved, and HO-1 expression was increased (P＜0.05) after curcumin treatement. In the curcumin treatment group, the protective effect of curcumin on liver injury could be reversed by HO-1 active inhibitor ZnPP.. Curcumin can improve liver inflammation and fibrosis caused by BDL, and this protective effect is related to the regulation of HO-1 activity by curcumin.

Topics: Animals; Cholestasis; Curcumin; Liver; Liver Cirrhosis; Male; Mice; Mice, Inbred BALB C; Treatment Outcome

Curcumin exerts hepatoprotective effects via poorly defined mechanisms. Recently, some studies suggested that this effect was mediated by antagonizing CB1 receptors in hepatic stellate cells. The current study aimed to investigate whether CB1 antagonist, hemopressin, could potentiate the hepatoprotective effect of curcumin, in comparison with silymarin in bile duct-ligated (BDL) rats. Curcumin and hemopressin each alone and in combination ameliorated biochemical and structural fibrotic injury, and downregulated cyclooxygenase-2 (COX-2) and both mRNA and protein levels of nuclear factor kappa B (NF-κB) in fibrotic liver. In contrast to the previous studies, curcumin alone did not affect the gene expression of cannabinoid receptors. However, the combination of hemopressin and curcumin reduced the expression of CB1 in fibrotic liver. Surprisingly, silymarin upregulated CB2 receptors and downregulated CB1 at mRNA level more than all the administered drugs. Both curcumin and hemopressin each alone decreased lipid peroxidation product, malondialdehyde (MDA), while the combination increased the reduced glutathione content. All the administered drugs increased the hepatic antiapoptotic marker, Bcl2. Our study suggests that hemopressin potentiates the hepatoprotective effect of curcumin on fibrotic liver. We identified a new mechanism of the hepatoprotective effect of silymarin via modulation of cannabinoid receptors in fibrotic liver.

Topics: Animals; Cholestasis; Curcumin; Cyclooxygenase 2; Drug Synergism; Glutathione; Hemoglobins; Lipid Peroxidation; Liver; Liver Cirrhosis; Male; NF-kappa B; Peptide Fragments; Proto-Oncogene Proteins c-bcl-2; Rats, Wistar; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; RNA, Messenger; Silymarin

Cholestasis is a clinically significant symptom and widely associated with liver diseases, however, there are very few effective therapies for cholestasis. Danning tablet (DNT, a Chinese patent medicine preparation) has been clinically used to treat human liver and gallbladder diseases for more than 20 years in China. However, which ingredients of DNT contributed to this beneficial effect and their mechanistic underpinnings have been largely unknown. In the present study, we discovered that DNT not only demonstrated greater benefits for cholecystitis patients after cholecystectomy surgery in clinic but also showed protective effect against alpha-naphthylisothiocyanate (ANIT)-induced cholestasis model in rodent. Curcumin, one major compound derived from DNT, exerted the protective effect against cholestasis through farnesoid X receptor (FXR), which has been focused as potential therapeutic targets for treating cholestasis. The underlying mechanism of curcumin against cholestasis was restoring bile acid homeostasis and antagonizing inflammatory responses in a FXR-dependent manner and in turn contributed to overall cholestasis attenuation. Collectively, curcumin can be served as a potential treatment option for liver injury with cholestasis.

Topics: 1-Naphthylisothiocyanate; Animals; Bile Acids and Salts; Cholestasis; Curcumin; Disease Models, Animal; HEK293 Cells; Humans; Inflammation; Mice; Mice, Knockout; Receptors, Cytoplasmic and Nuclear

We aimed to determine the effects of curcumin on liver fibrosis and to clarify the role of nuclear factor-κB (NF-κB) and inducible nitric oxide synthase (iNOS) in a model of microsurgical cholestasis in the early stage of extrahepatic biliary atresia. Twelve-week-old Wistar rats were divided into four groups (n = 8): sham-operated rats (received olive oil after laparotomy); a curcumin group (received curcumin, 200 mg kg(-1) per day, after laparotomy); a biliary duct ligated group (BDL, received olive oil after operation); and a biliary duct ligated/curcumin group (BDL curc, received curcumin, 200 mg kg(-1) per day, after operation). After 3 weeks of treatment, curcumin did not modify blood plasma markers as well as the expressions of iNOS and NF-κB (p65) in the livers of the sham group. Interestingly, there was a significant increase in the extent of both liver and kidney fibrosis. On the other hand, despite a decrease in the expression of iNOS and NF-κB (p65), treatment with curcumin did not affect fibrosis enlargement due to bile duct ligation in the liver. In the BDL group, treatment with curcumin decreased the level of blood plasma markers investigated. In conclusion, treatment with curcumin was able to improve the functional properties of hepatocytes and to inhibit the upregulations of both NF-κB and iNOS in the BDL group; however, no beneficial effect was observed on the liver fibrosis developed in this model of cholestasis. Thus, in the studied model of microsurgical cholestasis, other factors different from NF-κB and iNOS are responsible for fibrotic processes in the liver.

Topics: Animals; Bile Ducts; Cholestasis; Curcumin; Disease Models, Animal; Humans; Liver Cirrhosis; Male; NF-kappa B; Nitric Oxide Synthase Type II; Rats; Rats, Wistar

Curcumin, a most active antioxidant compound, has been suggested to have potential beneficial effects against most metabolic and psychological disorders, including cholestasis. In the present study, the effects of curcumin against oxidative stress and DNA damage induced by bile duct ligation (BDL) in Wistar albino rats for 14 days were investigated. The rats were divided into three following groups: Sham group, the BDL group and the BDL+curcumin group. A daily dose of 50mg/kg curcumin was given to the BDL+curcumin group intragastrically for 14 days. The biomarkers of hepatocellular damage were decreased in the BDL+curcumin group compared to the BDL group, indicating that curcumin recovered the liver functions. DNA damage as assessed by the alkaline comet assay was also found to be low in the BDL+curcumin group. Curcumin significantly reduced malondialdehyde and nitric oxide levels, and enchanced reduced glutathione levels and catalase, superoxide dismutase, and glutathione S-transferase enzymes activities in the livers and kidneys of BDL group. Curcumin treatment in BDL group was found to decrease tumor necrosis factor-alpha levels in the livers of rats. These results suggest that curcumin might have protective effects on the cholestasis-induced injuries in the liver and kidney tissues of rats.

Topics: Animals; Antioxidants; Bile Ducts; Catalase; Cholestasis; Curcumin; Disease Models, Animal; DNA Damage; Glutathione; Glutathione Transferase; Kidney; Liver; Male; Malondialdehyde; Nitric Oxide; Oxidative Stress; Protective Agents; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

The present study revealed the indirect effect of a turmeric (TUR) diet on the histopathological changes and proliferating cell nuclear antigen staining in Syrian hamsters with partial obstruction by liver fluke (Opisthorchis viverrini) infection and inflammation by N-nitrosodimethylamine (NDMA) administration. The result of the analysis of histopathological changes shows that a TUR diet has an anti-inflammatory property in the case of a single condition of NDMA administration or O. viverrini infection, as has been reported previously. Unfortunately, an adverse indirect effect of TUR was observed in the combination of infection with O. viverrini and administration of NDMA, with a 30-50% increase in new bile duct formation, correlated with an increase in proliferating cell nuclear antigen. Our present result suggests that the properties of curcumin are anti-inflammation and antioxidant including enhancing biliary contraction and bile flow. Thus, a combination of factors (treated with O. viverrini, NDMA, and TUR diet) result in an increasing bile duct proliferation which may cause from biliary homeostasis.

Topics: Animals; Anti-Inflammatory Agents; Bile Ducts; Cholestasis; Cricetinae; Curcuma; Diet; Dimethylnitrosamine; Fasciola hepatica; Inflammation; Mesocricetus; Opisthorchiasis; Opisthorchis

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cholestasis; Curcumin; Humans; Mice; Mice, Knockout; Phytotherapy; Plant Extracts

Curcumin is a phytophenolic compound, which is highly efficacious for treating several inflammatory diseases. The aim of this study was to evaluate the efficacy of curcumin in preventing or reversing liver cirrhosis. A 4-week bile duct ligation (BDL) rat model was used to test the ability of curcumin (100 mg/kg, p.o., daily) to prevent cirrhosis. To reverse cirrhosis, CCl(4) was administered chronically for 3 months, and then it was withdrawn and curcumin administered for 2 months. Alanine aminotransferase, gamma-glutamyl transpeptidase, liver histopathology, bilirubin, glycogen, reduced and oxidized glutathione, and TGF-beta (mRNA and protein) levels were assessed. Curcumin preserved normal values of markers of liver damage in BDL rats. Fibrosis, assessed by measuring hydroxyproline levels and histopathology, increased nearly fivefold after BDL and this effect was partially but significantly prevented by curcumin. BDL increased transforming growth factor-beta (TGF-beta) levels (mRNA and proteins), while curcumin partially suppressed this mediator of fibrosis. Curcumin also partially reversed the fibrosis induced by CCl(4). Curcumin was effective in preventing and reversing cirrhosis, probably by its ability of reducing TGF-beta expression. These data suggest that curcumin might be an effective antifibrotic and fibrolitic drug in the treatment of chronic hepatic diseases.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Cholestasis; Curcumin; Dose-Response Relationship, Drug; Drug Interactions; Liver Cirrhosis, Experimental; Male; Oxidative Stress; Rats; Rats, Wistar; Transforming Growth Factor beta

Curcumin, an anti-inflammatory and antioxidant compound, was evaluated for its ability to suppress acute carbon tetrachloride-induced liver damage. Acute hepatotoxicity was induced by oral administration of CCl4 (4 g/kg, p.o.). Curcumin treatment (200 mg/kg, p.o.) was given before and 2 h after CCl4 administration. Indicators of necrosis (alanine aminotransferase) and cholestasis (gamma-glutamyl transpeptidase and bilirubins) resulted in significant increases after CCl4 intoxication, but these effects were prevented by curcumin treatment. As an indicator of oxidative stress, GSH was oxidized and the GSH/GSSG ratio decreased significantly by CCl4, but was preserved within normal values by curcumin. In addition to its antioxidants properties, curcumin is capable of preventing NF-kappaB activation and therefore to prevent the secretion of proinflammatory cytokines. Therefore, in this study we determined the concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) mRNA, and NF-kappaB activation. CCl4-administered rats depicted significant increases in TNF-alpha, IL-1beta, and IL-6 production, while curcumin remarkably suppressed these mediators of inflammation in liver damage. These results were confirmed by measuring TNF-alpha, and IL-1beta protein production using Western Blot analysis. Accordingly, these proteins were increased by CCl4 and this effect was abolished by curcumin. Administration of CCl4 induced the translocation of NF-kappaB to the nucleus; CCl4 induced NF-kappaB DNA binding activity was blocked by curcumin treatment. These findings suggest that curcumin prevents acute liver damage by at least two mechanisms: acting as an antioxidant and by inhibiting NF-kappaB activation and thus production of proinflammatory cytokines.

Topics: Active Transport, Cell Nucleus; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Biomarkers; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Cell Nucleus; Cholestasis; Curcumin; Cytokines; Inflammation Mediators; Liver; Male; Necrosis; NF-kappa B; Oxidative Stress; Rats; Rats, Wistar

Xanthinoxidase (XO) derived radical species are involved in bacterial translocation (BT) in cholestatic rats. The mechanism by which XO influences remains unclear. It has been shown recently that nuclear factor-kappa B (NF-kappaB), a ubiquitous transcription factor, can be activated by oxidative stress and thereby promote the process of BT. We investigated the effects of NF-kappaB inactivation on the incidence of BT in cholestatic rats. Sprague-Dawley rats were randomly assigned to one of eight groups: groups 1-4 were sham laparotomized rats either untreated (S1) or treated for 5 days with thalidomide (S2), curcumin (S3), or Inchin-ko (ICK; S4); groups 5-8 underwent common bile duct ligation (CBDL) for 5 days and were either untreated (C1) or treated with thalidomide (C2), curcumin (C3), or ICK (C4). After 5 days bacteriological cultures were performed from portal blood and V. cava, from the central mesenteric lymph node complex (MLN), spleen, and liver. The intensity of the activated NF-kappaB-subunit p65/p50 in the ileum mucosa was estimated by light microscopy and a scoring system from 1 to 20. Malondialdehyde (MDA) and myeloperoxidase activity (MPO) in the ileum were evaluated and expressed as U/g dry weight. Thalidomide and ICK reduced in CBDL-rats significantly the BT rate (63% vs. 18%, 63% vs. 30%, P<0.01). Enzyme estimations (MDA, MPO, and GSH) in sham operated animals showed no significant changes in the untreated groups compared with the treated groups. CBDL-rats pre-treatment with all three compounds caused a significant increase of MDA levels if groups were compared with the untreated C1-group (C1 31.6+/-7.7, C2 54.5+/-12.2, C3 53.3+/-11.2, and C4 47.2+/-9.4). GSH was reduced after the pre-treatment by all compounds but only significantly after curcumin pre-treatment (C1 vs. C3: 13.9+/-1.8 vs. 7.1+/-1.8; P<0.05). MPO estimations were significantly higher in the untreated C1-group if compared with groups C2, C3, and C4 (C1 1036.4+/-340.9, C2 709.9+/-125.9, C3 545.2+/-136.6, and C4 556.7+/-247.4; P<0.05). Thalidomide inhibited significantly the activation of NF-kappaB (C2 vs. C1: 6.0+/-4.5 vs. 12.7+/-5.3; P<0.01). Likewise, Curcumin and ICK suppressed NF-kappaB activation, but this did not reach significance in this experiment. NF-kappaB is involved in the process of BT in cholestatic rats and may be activated by XO derived ROS. We assume that the activated NF-kappaB initiates transcription of target genes inducing cytokine production, which in

Topics: Analysis of Variance; Animals; Bacterial Translocation; Cholestasis; Curcumin; Drugs, Chinese Herbal; Glutathione; Ileum; Lipid Peroxidation; Male; Malondialdehyde; Neutrophil Activation; NF-kappa B; Peroxidase; Random Allocation; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Signal Transduction; Thalidomide; Xanthine Oxidase

Apoptosis induced by toxic bile acids is thought to contribute to liver injury during cholestasis. The transcription factor AP-1 is involved in the induction of apoptosis depending on stimulus and cell type. It is not known whether the major human toxic bile acid, glycochenodeoxycholic acid (GCDCA), modulates AP-1 in hepatocytes. Our data show that GCDCA (75 microM, 4 h) significantly upregulates cFos and JunB as demonstrated by microarray analysis and real-time PCR in HepG2-Ntcp hepatoma cells. GCDCA (75 microM, 4 h) also induced AP-1 activation as determined by EMSA that was most distinct after 30 min. In parallel, AP-1 transcriptional activity increased by 40% after exposure to GCDCA. Curcumin, an AP-1 inhibitor, dose-dependently reduced (1-25 microM) or completely abolished (50 microM) the apoptotic effect of GCDCA. Thus, GCDCA-induced upregulation of AP-1-dependent genes appears important for the cytotoxicity of this bile acid.

Topics: Amino Acid Chloromethyl Ketones; Apoptosis; Bile Acids and Salts; Cell Line; Cell Line, Tumor; Cholestasis; Curcumin; Detergents; Dose-Response Relationship, Drug; Enzyme Inhibitors; Genes, Reporter; Glycochenodeoxycholic Acid; Hepatocytes; Humans; Immunoblotting; Liver; Luciferases; MAP Kinase Signaling System; Oligonucleotide Array Sequence Analysis; p38 Mitogen-Activated Protein Kinases; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Taurocholic Acid; Time Factors; Transcription Factor AP-1; Transcription, Genetic; Up-Regulation

Former studies have shown that curcumin, which can be extracted from different Curcuma species, is able to stimulate bile flow and to reduce hypercholesterolemia. We investigated in a subchronic bile fistula model the ability of curcumin to reduce cyclosporine-induced cholestasis and hypercholesterolemia. Male Wistar rats were daily treated with curcumin (100 mg/kg p. o.), cyclosporine (10 mg/kg i. p.), and a combination of curcumin with cyclosporine. After two weeks a bile fistula was installed into the rats to measure bile flow and biliary excretion of bile salts, cholesterol, bilirubin, cyclosporine and its main metabolites. Blood was taken to determine the concentration of these parameters in serum or blood. Cyclosporine reduced bile flow (-14 %) and biliary excretion of bile salts (-10 %) and cholesterol (-61 %). On the other hand, cyclosporine increased serum concentrations of cholesterol and triglycerides by 32 % and 82 %, respectively. Sole administration of curcumin led to a slight decrease of bile flow (-7 %) and biliary bile salt excretion (-12 %), but showed no effect on biliary excretion of cholesterol and serum lipid concentration. When curcumin was given simultaneously with cyclosporine, the cyclosporine-induced cholestasis was enhanced but the cyclosporine-induced hyperlipidemia was not affected. Neither the biliary excretion nor the blood concentration of cyclosporine was influenced by curcumin. The blood concentration of the main cyclosporine metabolites, however, was lowered by half while their biliary excretion was strongly increased by curcumin. From these results we conclude that curcumin is not able to prevent cyclosporine-induced cholestasis and hyperlipidemia after prolonged administration in bile fistula rats.

Topics: Administration, Oral; Animals; Bile; Bile Acids and Salts; Biliary Fistula; Cholagogues and Choleretics; Cholestasis; Cholesterol; Curcuma; Curcumin; Cyclosporine; Disease Models, Animal; Hypercholesterolemia; Hypolipidemic Agents; Immunosuppressive Agents; Injections, Intraperitoneal; Male; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Triglycerides

We investigated the ability of curcumin, which can be extracted from different Curcuma species, to prevent cyclosporin-induced reduction of biliary bilirubin and cholesterol excretion, and its influence on biliary excretion of cyclosporin (CS) and its metabolites in the bile fistula model in rats. I.v. injection of curcumin (25 and 50 mg/kg) after 30 min increased dose-dependently basal bile flow (30 microliters/kg/min) up to 200%, biliary bilirubin excretion (3000 pmol/kg/min) up to 150%, and biliary cholesterol excretion (22 nmol/kg/min) up to 113%. CS (30 mg/kg) reduced bile flow to 66% and biliary excretion of bilirubin and of cholesterol to 33% of the basal value 30 min after i.v. injection. I.v. administration of curcumin (25 and 50 mg/kg) 30 min after CS increased bile flow dose dependently again to 130% for 1 hour and biliary excretion of cholesterol and of bilirubin to 100% of the basal value for 30 and 150 min, respectively. Injection of curcumin 15 min before CS prevented the CS-induced drop of bile flow at 50 mg/kg and reduction of biliary bilirubin excretion already at 25 mg/kg until the end of the experiment (180 min). The CS-induced reduction of biliary cholesterol excretion, however, was not prevented by curcumin. Finally, the biliary excretions of CS (1200 ng/kg/min) and its metabolites (1200 ng/kg/min) were slightly reduced by curcumin at a dose of 50 mg/kg (to 83% of the initial values). The clinical importance of these controversial effects remains to be shown.

Topics: Animals; Bile; Bilirubin; Cholagogues and Choleretics; Cholestasis; Cholesterol; Curcumin; Cyclosporine; Injections, Intravenous; Male; Rats; Rats, Wistar

Former studies have shown that curcumin, which can be extracted from different Curcuma species, is able to stimulate bile flow in rats, whereas bisdemethoxycurcumin, which is mainly found in rhizomes of Curcuma longa, is believed to inhibit bile flow. To reevaluate this observation we investigated the influence of both curcuminoids on bile flow, bile acid concentration and excretion over a time period of 180 min in the bile fistula model in rats. Furthermore, we tested the ability of both curcuminoids to reduce cyclosporin-induced cholestasis. 30 min after intravenous injection of 25 mg/kg of curcumin and bisdemethoxycurcumin bile flow was enhanced from 500 microliters/kg/15 min (100%) to 180% and to 220%, respectively. The choleretic effect of bisdemethoxycurcumin lasted longer than that of curcumin. Following intravenous injection of 30 mg/kg of cyclosporin, which reduced bile flow, bile acid concentration (15 mmol/l) and excretion (12.5 mumol/kg/15 min) to 40% of the initial value, administration of curcumin and bisdemethoxycurcumin transiently increased bile flow to 100% and to 125% of the starting value, respectively. However, only bisdemethoxycurcumin statistically significantly attenuated cyclosporin-induced reduction of bile acid excretion. We conclude that the beneficial properties of curcuminoids for the therapy of cyclosporin-induced cholestasis still remain to be proven.

Topics: Animals; Bile; Cholagogues and Choleretics; Cholestasis; Coumaric Acids; Curcumin; Cyclosporine; Diarylheptanoids; Immunosuppressive Agents; Male; Rats; Rats, Wistar