Curcumin in Hepatobiliary Disease: Pharmacotherapeutic Properties and Emerging Potential Clinical Applications.

Curcumin, an aromatic phytoextract from the turmeric (Curcuma longa) rhizome, has been used for centuries for a variety of purposes, not the least of which is medicinal. A growing body of evidence suggests that curcumin has a broad range of potentially therapeutic pharmacological properties, including anti-inflammatory, anti-fibrotic, and anti-neoplastic effects, among others. Clinical applications of curcumin have been hampered by quality control concerns and limited oral bioavailability, although novel formulations appear to have largely overcome these issues. Recent in vitro and in vivo studies have found that curcumin's cytoprotective and other biological activities may play a role in an array of benign and malignant hepatobiliary conditions, including but not limited to non-alcoholic fatty liver disease, cholestatic liver disease (e.g. primary sclerosing cholangitis), and cholangiocarcinoma. Here we provide an overview of fundamental principles, recent discoveries, and potential clinical hepatobiliary applications of this pleiotropic phytocompound.

[THE POSSIBILITY OF DIET THERAPY AND TYPICAL ERRORS IN THE NUTRITION OF PATIENTS WITH BILIARY TRACT DISEASES].

This lecture for the doctors considered the possibility of using power to influence the basic mechanisms of pathogenesis in diseases of the biliary: cholestatic syndrome, impaired physical-chemical properties of bile, inflammation, biliary tract and intestines motor activity disfunction. The clinical case analyzed typical mistakes in nutrition of patients with disorders of the biliary tract.

Characterization of acute biliary hyperplasia in Fisher 344 rats administered the indole-3-carbinol analog, NSC-743380.

NSC-743380 (1-[(3-chlorophenyl)-methyl]-1H-indole-3-carbinol) is in early stages of development as an anticancer agent. Two metabolites reflect sequential conversion of the carbinol functionality to a carboxaldehyde and the major metabolite, 1-[(3-chlorophenyl)-methyl]-1H-indole-3-carboxylic acid. In an exploratory toxicity study in rats, NSC-743380 induced elevations in liver-associated serum enzymes and biliary hyperplasia. Biliary hyperplasia was observed 2 days after dosing orally for 2 consecutive days at 100mg/kg/day. Notably, hepatotoxicity and biliary hyperplasia were observed after oral administration of the parent compound, but not when major metabolites were administered. The toxicities of a structurally similar but pharmacologically inactive molecule and a structurally diverse molecule with a similar efficacy profile in killing cancer cells in vitro were compared to NSC-743380 to explore scaffold versus target-mediated toxicity. Following two oral doses of 100mg/kg/day given once daily on two consecutive days, the structurally unrelated active compound produced hepatic toxicity similar to NSC-743380. The structurally similar inactive compound did not, but, lower exposures were achieved. The weight of evidence implies that the hepatotoxicity associated with NSC-743380 is related to the anticancer activity of the parent molecule. Furthermore, because biliary hyperplasia represents an unmanageable and non-monitorable adverse effect in clinical settings, this model may provide an opportunity for investigators to use a short-duration study design to explore biomarkers of biliary hyperplasia.

Ingredients of Huangqi decoction slow biliary fibrosis progression by inhibiting the activation of the transforming growth factor-beta signaling pathway.

BACKGROUND: Huangqi decoction was first described in Prescriptions of the Bureau of Taiping People's Welfare Pharmacy in Song Dynasty (AD 1078), and it is an effective recipe that is usually used to treat consumptive disease, anorexia, and chronic liver diseases. Transforming growth factor beta 1 (TGFß1) plays a key role in the progression of liver fibrosis, and Huangqi decoction and its ingredients (IHQD) markedly ameliorated hepatic fibrotic lesions induced by ligation of the common bile duct (BDL). However, the mechanism of IHQD on hepatic fibrotic lesions is not yet clear. The purpose of the present study is to elucidate the roles of TGFß1 activation, Smad-signaling pathway, and extracellular signal-regulated kinase (ERK) in the pathogenesis of biliary fibrosis progression and the antifibrotic mechanism of IHQD. METHODS: A liver fibrosis model was induced by ligation of the common bile duct (BDL) in rats. Sham-operation was performed in control rats. The BDL rats were randomly divided into two groups: the BDL group and the IHQD group. IHQD was administrated intragastrically for 4 weeks. At the end of the fifth week after BDL, animals were sacrificed for sampling of blood serum and liver tissue. The effect of IHQD on the TGFß1 signaling pathway was evaluated by western blotting and laser confocal microscopy. RESULTS: Decreased content of hepatic hydroxyproline and improved liver function and histopathology were observed in IHQD rats. Hepatocytes, cholangiocytes, and myofibroblasts in the cholestatic liver injury released TGFß1, and activated TGFß1 receptors can accelerate liver fibrosis. IHQD markedly inhibited the protein expression of TGFß1, TGFß1 receptors, Smad3, and p-ERK1/2 expression with no change of Smad7 expression. CONCLUSION: IHQD exert significant therapeutic effects on BDL-induced fibrosis in rats through inhibition of the activation of TGFß1-Smad3 and TGFß1-ERK1/2 signaling pathways.

Optimizing nutritional management in children with chronic liver disease.

Malnutrition is common in infants and children with chronic liver disease (CLD) and may easily be underestimated by clinical appearance alone. The cause of malnutrition in CLD is multifactorial, although insufficient dietary intake is probably the most important factor and is correctable. Fat malabsorption occurs in cholestatic disorders, and one must also consider any accompanying fat-soluble vitamin and essential fatty acid deficiencies. The clinician should proactively evaluate, treat, and re-evaluate response to treatment of nutritional deficiencies. Because a better nutritional state is associated with better survival before and after liver transplantation, aggressive nutritional management is an important part of the care of these children.

[Non-medicamentous correction of metabolic and functional disorders in the biliary tract of patients with metabolic syndrome].

This study included 49 patients with coronary heart disease (CHD) and arterial hypertension (AH) in whom comprehensive medical examination revealed metabolic syndrome (MA). The objective of the work was to ascertain the possibility of therapy courses using chloride-hydrocarbonate-sodium mineral water and to evaluate its corrective effect on metabolic processes and functional disturbances of the biliary tract. It was shown that mineral water has beneficial effect in patients with functional incompetence of the biliary tract. Elimination of pain syndrome and resolution of dyspeptic symptoms was associated with the improvement of physico-chemical characteristics of the bile in the majority of the patients. These changes developed 1.5-2 times sooner than in the absence of therapy which substantially improved quality of life of the patients. Another positive result of mineral water consumption was the reduced level of blood lipids, in the first place that of total cholesterol and triglycerides. The efficiency of corrective action of non-medicamentous treatment modalities, such as courses of intake of chloride-hydrocarbonate-sodium mineral water, in patients with functional disturbances of the biliary tract is comparable with that of recommended drug therapy. The hypolipidemic effect of chloride-hydrocarbonate-sodium mineral water demonstrated in the present study allows it to be recommended as a tool for non-medicamentous correction of hyperlipidemia known to be not only a risk factor of CHD and AH but also as a constituent component of metabolic syndrome. The data obtained suggest the possibility to improve efficiency of the treatment of motor dysfunction of the biliary tract and metabolic disorders inherent in metabolic syndrome.

[Correction of disorders of bile lipid-mineral composition as a method of preventing cholelithiasis]. / Korrektsiia narushenii lipidno-mineral'nogo sostava zhelchi kak metod profilaktiki zhelchnokamennoi bolezni.

A study of 60 patients with biliary tract diseases revealed different disorders of the lipid and mineral composition of bile of monotypical character but different by severity in patients with dyskinesias, cholecystitis and cholelithiasis. Silibor favours normalization of the lipid composition of bile, a dry protein mixture--the mineral composition quadevit--the mineral and lipid composition of bile.

[Clinical studies on the biliary excretion of mezlocillin, especially in cases with liver dysfunction].

To investigate efficacy of mezlocillin (MZPC) in the treatment of biliary tract infection, the time course concentrations of MZPC in the bile of patients with, in particular, liver dysfunction were measured. MZPC concentrations in the bile decreased with the increase in the severity of liver dysfunction. However, the bile concentration was maintained more than 50 micrograms/ml even in cases of severe cholangitis with obstructive jaundice. These results indicate that MZPC is an useful antibiotic for the treatment of biliary tract infection.

Hyperparathyroidism in hepatobiliary disease in infancy.

Metabolism of calcium and magnesium may be disturbed in hepatobiliary disease because of deficient or absent bile flow into the gut, since bile is important for the intestinal absorption of these elements. In the present paper the tubular reabsorption of phosphate (TRP), calcium (TRCa), and magnesium (TRMg) were determined in an attempt to evaluate the parathyroid function of infants and children with hepatobiliary disease. In unrepaired biliary atresia TRP was conspicuously reduced (mean 49.8%, SD 15.1). In successfully repaired biliary atresia the value was increased near the normal range (mean 80.7%, SD 8.1). In neonatal hepatitis the value was variable in individual cases, but significantly lower than the normal (mean 47.6%, SD 19.9). TRCa was reduced in one third of the patients with unrepaired biliary atresia and in one fifth of the cases of neonatal hepatitis. The value was within the normal range in repaired biliary atresia. TRMg was decreased in both unrepaired and repaired biliary atresia and in neonatal hepatitis. The effect of intravenous calcium infusion on TRP, TRCa and TRMg was evaluated in 3 patients with unrepaired biliary atresia. TRP was conspicuously enhanced after infusion. TRCa was decreased in 3 to a variable extent. TRMg was moderately increased in 2 and greatly decreased in 1. These results indicate that infants with hepatobiliary disease are in a state of secondary hyperparathyroidism because of deficient or absent bile flow into the intestines.