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.

Castanea sativa Mill. extract contracts gallbladder and relaxes sphincter of Oddi in guinea pig: a natural approach to biliary tract motility disorders.

Impaired gallbladder motility is a contributing factor to gallstone formation. Since many drugs delaying intestinal motility inhibit gallbladder emptying, the aim of the present study was to evaluate the effect on gallbladder and sphincter of Oddi motility of a Natural Chestnut Wood Extract (NEC) that reduces intestinal motility. In order to evaluate the effect of the extract in normal- and high-risk gallstone conditions, the investigation was performed using tissues from animals fed normal and lithogenic diet. Fifty guinea pigs were administered either control or lithogenic diet. The spontaneous motility of the gallbladder and sphincter of Oddi were recorded on isolated gallbladder tissues; thereafter, the effect of NEC on motility was tested and compared with carbachol (CCh), potassium chloride (KCl), noradrenaline (NA), and A71623. Compared to controls, the lithogenic diet induced an irregular and disordered motor pattern in both the gallbladder and sphincter of Oddi. NEC increased gallbladder and decreased sphincter of Oddi spontaneous motility independently of cholinergic, adrenergic, and CCK-1 receptor-mediated pathways both in controls and in lithogenic diet-fed animals, although the effect was lower in the latter group. The effect was reversible and mediated by calcium channels. The natural extract of chestnut increasing gallbladder contraction and inducing the relaxation of the sphincter of Oddi can be of benefit in pathological conditions associated with increased transit time at risk of gallstones.

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.

Cholestasis induced by total parenteral nutrition: effects of the addition of Taurine (Tauramin®) on hepatic function parameters; possible synergistic action of structured lipids (SMOFlipid®).

OBJECTIVE: Assess the hepatoprotective effect of Taurine (Tau) in cases of hepatic cholestasis induced by Total Parenteral Nutrition (TPN). METHODS: We describe a retrospective series of 54 patients who received TPN, in which cholestasis was detected at an (Intermediate) point that separates the duration of TPN into 2 Phases. From this moment -Phase 2- on, and according to clinical criteria, some patients (Group A, n = 27) received amino acids with Tau (22.41 ± 3.57 mg/kg/day)(Tauramin®), while the rest (Group B, n = 27) received the standard solution without Tau. The mean TPN durations were 39.2 ± 17.1 and 36.4 ± 18.1 days respectively, with the Intermediate points on days 19.56 ± 10.51 and 17.89 ± 11.14. They all received diets that were homogeneous in terms of kcal and macronutrients. In Phase 2, 21 patients from Group A received structured lipids (SMOFlipid®); while 20 from Group B received soy MCT/LCT [ Medium Chain Triglycerides/Long Chain Triglycerides ] (physical or structured mixture). In a retrospective study, differences could not be avoided. The analytical parameters from three periods (Initial, Intermediate, and Final) were obtained from Nutridata® and Servolab®. We compared interperiod values using the Wilcoxon test SPSS® (p < 0.05). RESULTS: After introducing Taurine AST, ALT, and GGT were significantly reduced; Bilirubin was also reduced, but not significantly. The values obtained for GGT in Group A were (Mean(σ)/median): Initial 48.6 (23.1)/46; Intermediate 473.7 (276.2)/438, and Final 328.9 (190.4)/305. We stress that the mean GGT value is reduced by 30.56% after adding Taurine, while in its absence all parameters are elevated, and mean GGT increases 45.36%. CONCLUSION: These results show Taurine's hepatoprotective effect and support its use in cases of TPN-induced cholestasis. We acknowledge the possibility that the differences between SMOF and the MCT/LCT mixtures also may have influenced the results in a combined effect with taurine.

Use and safety perception of herbal remedies in patients with liver/biliary tract disorders: an Italian study.

BACKGROUND: Use of herbal remedies (HR) has increased in the general population, particularly among patients with chronic diseases. Marketing of HR is usually regulated by imperfect standards, and the reporting of HR-related adverse reactions has increased. Studies assessing prevalence of HR use among patients with liver/biliary tract disorders are limited and no data are available in Italy. Aims of this study were to assess the prevalence of HR use, the clinical and demographic variables of HR users, and to evaluate their safety perception about HR. STUDY: From October 1, 2007 to April 30, 2008, 231 consecutive patients attending the Liver Disease Unit clinic at Sant'Andrea Hospital, II Faculty of Medicine "La Sapienza" Rome, were interviewed using an ad hoc developed questionnaire. The questionnaire addressed the following items: demographic and clinical characteristics, use of conventional therapy, use of HR and safety perception. Data were expressed as mean (+/-SD) or number/total, and evaluated by student t and chi2 tests; univariate analysis and multivariate logistic regression (MLR) were conducted. RESULTS: Prevalence of HR use was 35.5%. HR use was more common among women (P=0.01), and in patients attending sports activity (P=0.03). 72% of patients using HR had never considered potentially harmful HR-side effects or interactions. Sixty-seven percent used HR in addition to conventional therapy. CONCLUSIONS: More than a third of patients attending Liver/Biliary Disorders Clinic uses HR. Misconceptions about HR safety is common.

[A clinical study of bile cultures and antibiotic susceptibility test in the patients with operation on biliary tract].

OBJECTIVE: To illustrate the bacteriology and their susceptibility to antibiotics in patients with biliary tract diseases and provide information for antibiotic choices. METHODS: The bile specimens were cultured and pathogens' susceptibility to antibiotics was obtained intraoperatively from 195 patients undergoing operations on biliary tract and 24 healthy liver donors from June 2007 to March 2008. RESULTS: Among 195 bile specimens collected from the patients intraoperatively, 44 ones were found bacterial growth by culture (22.6%), in which 11 ones were mixed infections (25.0%). Fifty-five bacterial strains belonging to 16 species were identified from these bile specimens. They included 34 Gram negative strains (61.8%), 19 Gram positive strains (34.6%) and 2 fungal strains (3.6%). The commonest pathogens were Escherichia coli (27.3%), Enterobacter cloacae (12.7%), Enterococcus faecalis (12.7%) and Enterococcus faecium (10.9%). Among 24 bile specimens collected from the healthy liver donors, one was found Escherichia coli growth by culture (4.2%). The results of susceptibility test showed that the resistant rates of Gram negative strains to Meropenem was 2.8%, followed by Imipenem (5.6%), Sulperazone (22.8%) and Amikacin (28.7%). In this study Gram negative strains were highly resistant to Penicillins, Quinolones, some third generation Cephalosporins and so on (>50.0%). None of Gram positive strains were resistant to Vancomycin and Teicoplanin. They were highly resistant to Penicillins, Quinolones, Clindamycin and so on (>40.0%). CONCLUSIONS: (1) Gram negative strains remain the commonest pathogens in biliary tract infection in Renji Hospital and the commonest pathogen is Escherichia coli. The infection of enterococcus is going up. The mixed infection cases happen mostly in acute biliary infection. (2) To treat biliary infection the broad-spectrum antibiotics which are effective to Escherichia coli are optimal choices. Ceftazidime or Ciprofloxacin may be used in mild biliary infection. Sulperazone or Amikacin may be used in severe biliary infection. Imipenem and Vancomycins may be used as second choice to treat the infection which other drugs are ineffective to.

Therapeutic use of cytoprotective agents in canine and feline hepatobiliary disease.

Many medicinal, nutraceutical, and botanic extracts have been used as cytoprotective agents in liver disease. This article explains the mechanisms of action, pertinent pharmacokinetics, side effects, and clinical indications for the use of S-adenosylmethionine, N-acetylcysteine, ursodeoxycholic acid, silymarin, and vitamin E. The literature pertaining to in vitro studies, laboratory animal models, and human and veterinary clinical trials is reviewed with regards to the efficacy and use of these cytoprotective agents in hepatobiliary disease.

Achillea millefolium L. s.l. revisited: recent findings confirm the traditional use.

Yarrow (Achillea millefolium L. s.l.) is traditionally used in the treatment of inflammatory and spasmodic gastro-intestinal disorders, hepato-biliary complaints and inflammation. Now we could show that the flavonoids mediated the antispasmodic properties of yarrow, whereas the dicaffeoylquinic acids caused the choleretic effects. Moreover, we observed an in vitro-inhibition of human neutrophil elastase, a protease involved in the inflammatory process, by extracts and fractions from yarrow, which suggests additional mechanisms of antiphlogistic action. The presented results confirm the traditional use of yarrow.

Complementary healthcare practices.

This column provides a brief overview of the historical use of herbs for hepatobiliary disease. It includes information regarding both the harmful and helpful effects of herbs on the hepatobiliary system. Certainly more research is needed. Studies are currently in progress, many funded by grants from various agencies including the National Institute of Health. Since one-third of patients attending liver clinics are using these potentially helpful or harmful herbs, it is an important issue for gastroenterology nurses, associates, and other health care providers to address. We must increase our knowledge, advocate for safety and research, and discuss the use of herbs in a non-judgmental, informed manner.

[Galstena therapy of some hepatobiliary diseases]. / Galstena v lechenii nekotorykh zabolevanii pecheni i zhelchnykh putei.

Galstena was given to 10 patients with chronic cholecystitis, 15 patients with chronic hepatitis and 15 patients with fatty degeneration of the liver for 30 days in a dose 10 drops 3 times a day 30 min before meal. The effect of the drug was assessed in relation to biliary inflammation and motility, inflammation and metabolism in a hepatic cell. It was found that galstena improves motor function of the biliary tract and exocrine function of the liver, reduces activity of mesenchymo-inflammatory syndrome and fatty degeneration of the liver.

Cefepime for infections of the biliary tract.

Antibiotic treatment of biliary tract infections is widely accepted. An open, prospective, randomized, multicenter trial comparing cefepime (2 grams every 12 hours) with gentamicin (1.5 milligrams per kilograms every eight hours) plus mezlocillin (3 grams every four hours) for a minimum of five days was undertaken. Of the 149 patients enrolled, 120 were evaluable; 80 were randomized to receive cefepime and 40 were randomized to receive gentamicin plus mezlocillin (two to one randomization schedule). The diagnosis was acute cholecystitis in 101 patients and acute cholangitis in the remainder. There were no differences between the two treatment groups with regard to gender, age, disease, signs and symptoms, admitting temperature or laboratory values. All patients (100 percent) treated with gentamicin and mezlocillin were cured of the infection, as were 78 (97.5 percent) of the patients treated with cefepime (difference not significant). The incidence and spectrum of adverse events and complications were similar between the two groups (8.8 percent for cefepime versus 10 percent for gentamicin and mezlocillin). Our data show that the efficacy and safety of cefepime administered every 12 hours is equivalent to that of gentamicin and mezlocillin combination for treating patients with acute infections of the biliary tract. In addition, twice-daily administration of cefepime may be more cost-effective than the aminoglycoside-based combination.

[Polyunsaturated phosphatidylcholine combined with vitamin B complex in the treatment of patients with disorders of the hepatobiliary function caused by unbalanced nutrition]. / La fosfatidilcolina polinsatura associata a complesso vitaminico B nel trattamento dei danni della funzione epato-biliare da alimentazione squilibrata.

The above study was undertaken in order to assess the therapeutic activity of polyunsaturated phosphatidylcholine combined with vitamin B complex in 20 patients suffering from hepatobiliary disorders related to unbalanced diets with inappropriate caloric and/or macronutrient intake (another group of 20 subjects served as controls). The results obtained show that the combination used is apt to bring about desirable changes in the liver function parameters studied. These favorable changes are likely to be attributable to a reduction of damage to membranes and of changes in liver phospholipid synthesis.