Clinical effect of the extract of TCM Fructus akebiae combined with ursodeoxycholic acid on nonalcoholic fatty liver disease.

.Fructus akebiae extract (FAE) is a commonly used drug in the clinical treatment of liver cancer. FAE has many pharmacological activities, such as liver protection, anti-tumor, spasmolysis, pain relief and antifungal activity. Its clinical application is extensive, so far no toxic reports have been reported, and new drugs can be developed. This study was designed to investigate the therapeutic effect of predictor extract on non-alcoholic fatty liver disease (NAFLD). 180 patients with NAFLD were randomly divided into 2 groups. The control group was treated with ursodeoxycholic acid (UDCA), and the experimental group was treated with Fructus akebiae extract combined with ursodeoxycholic acid. The results showed that the comprehensive clinical efficacy of the treatment group was 95.56%, which was higher than that of the control group (93.33%), and P < 0.01. In the experimental group, 63 cases (70%) were improved after one course of treatment, main symptom score as (5.09 ±3.98), body mass index as (24.65±3.86), and liver CT value increased. It can be seen that the addition of FAE can significantly improve the clinical symptoms and serum biochemical indicators such as ALT, AST, TG and TC in patients with non-alcoholic fatty liver disease, which is supported by some histological evidence. These findings suggest that FAE combined with Ursodeoxycholic Acid is safe and effective in the treatment of fatty liver.

Pharmacokinetic Characteristics of Baicalin in Rats with 17α-ethynyl-estradiol-induced Intrahepatic Cholestasis.

Baicalin is one of the main active ingredients of choleretic traditional Chinese medicine drug Radix Scutellariae. The aim of this study was to explore the pharmacokinetic characteristics of baicalin in rats with 17α-ethynylestradiol (EE)-induced intrahepatic cholestasis (IC) based on its choleretic effects. Firstly, rats were subcutaneously injected with EE solution (5 mg/kg, 0.25 mL/100 g) for 5 consecutive days to construct an IC model. Then the bile excretion rate, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bile acid (TBA) and pathological changes of the liver were detected. Secondly, after successfully modeling, the rats were intragastrically given baicalin solution (200 mg/kg) (n=6). Blood samples were collected from the tail vein at different time points after intragastric administration. The protective effects of low- (50 mg/kg), medium- (100 mg/kg) and high-dose (200 mg/kg) baicalin on the liver in IC rats were evaluated. The content of baicalin in plasma was detected by liquid chromatography-mass spectrometry/mass spectrometry and pharmacokinetics parameters were calculated. Pharmacodynamic results showed that low-, medium- and high-dose baicalin all significantly increased the average excretion rate of bile (P<0.05), and significantly decreased serum levels of ALT, AST and ALP and TBA (P<0.05). Meanwhile, HE staining showed that baicalin significantly relieved EE-induced hepatocyte edema and necrosis. Pharmacokinetic results exhibited that the absorption of baicalin in both IC and normal control rats showed bimodal phenomenon. Cmax, AU(0-t) and AUC(0-∞) of baicalin in IC rats were significantly higher than those of the normal control group (P<0.01). T1/2 of plasma baicalin in the model group was significantly extended to (11.09±1.84) h, with clearance dropping to 61.78% of that of the normal control group (P<0.01). The above results suggested that baicalin had protective effects on the liver of IC rats, accompanied by significantly increased in vivo exposure, delayed in vivo clearance and markedly alterative pharmacokinetic characteristics. This study provides a theoretical basis for further development of baicalin as a feasible drug for treating IC.

An open-label randomized control study to compare the efficacy of vitamin e versus ursodeoxycholic acid in nondiabetic and noncirrhotic Indian NAFLD patients.

BACKGROUND/AIM: The study was carried out to compare the efficacy of Vitamin E versus Ursodeoxycholic acid (UDCA) in nondiabetic nonalcoholic fatty liver disease (NAFLD) patients. PATIENTS AND METHODS: We randomized 250 non cirrhotic and non diabetic NAFLD patients diagnosed on ultrasound, with raised alanine aminotransferase (ALT) level. (>40 IU/L), to receive Vitamin E 400 mg twice a day (Group A) or UDCA 300 mg twice a day (Group B) for 52 weeks. Lifestyle modification to achieve at least 5% weight reduction and subsequent weight control and regular exercise was advised to both groups. The primary study endpoint was normalization of ALT. Secondary endpoints were the proportion of patients with reduction in ALT, relative reduction in the NAFLD Fibrosis score (NFS), symptomatic improvement and tolerability. RESULTS: One hundred and fifty patients received UDCA as compared to 100 patients receiving Vitamin E. The treatment groups were comparable at entry with regard to age (44.1 vs 42.4 years), gender (67% vs 63% female), risk factors for nonalcoholic steatohepatitis, hypochondriac pain, serum liver biochemistries, and NAFLD Fibrosis score. The primary endpoint was achieved in 21 (14%) and 19 (19%) of patients in Group A and Group B, respectively (P = 0.2). The proportion of patients with reduction in ALT (56% vs 63%, P = 0.2), symptomatic improvement (78% vs 67%, P= 0.058), reduction in the NFS (44% vs 47%, P= 0.69), and tolerability (98% vs 95%, P= 0.2) were similar between Group A and Group B, respectively. CONCLUSION: UDCA is an effective and safe alternative to Vitamin E in nondiabetic-noncirrhotic Indian NAFLD patients.

Effect of Ursodeoxycholic Acid on Indirect Hyperbilirubinemia in Neonates Treated With Phototherapy.

BACKGROUND: Hyperbilirubinemia is a common neonatal problem. The present study aimed to investigate the effect of ursodeoxycholic acid in reducing indirect hyperbilirubinemia of infants under phototherapy. METHODS: This double-blind randomized clinical trial was conducted on neonates with jaundice, who had received phototherapy in the hospitals affiliated with the Shiraz University of Medical Sciences in 2013. A total of 80 neonates were enrolled in the study and were randomly divided into 2 groups. The intervention group (n =  0) with indirect hyperbilirubinemia received 10 mg · kg(-1) · day(-1) divided every 12 hours Ursobil (capsule 300 mg) in addition to phototherapy, whereas the control group (n =  0) received only phototherapy. Total bilirubin levels were measured every 12 hours until reaching <10 mg/dL, and then phototherapy was disrupted. The duration of phototherapy was measured. The 2 groups were compared regarding total bilirubin levels at different time points and duration of phototherapy using the generalized estimating equation (GEE) test. RESULTS: The mean of total bilirubin in the intervention group was 12 ± 1.6, 10 ± 1.1, and 9.8 ± 0.2 mg/dL 12, 24, and 48 hours after the beginning of phototherapy, respectively. On the contrary, these measures were 14.4 ± 1.3, 12.5 ± 1.4, and 10.1 ± 1.1 mg/dL in the control group, respectively, (P < 0.05). The mean time required for phototherapy to decrease the bilirubin level to < 10 mg/dL was 15.5 ± 6 and 44.6 ± 13.3 hours in the case and the control group, respectively, (P = 0.001). CONCLUSIONS: Ursodeoxycholic acid had additive effect with phototherapy in neonates with indirect hyperbilirubinemia. This drug also reduced the time period needed for phototherapy and, consequently, decreased the hospitalization period.

Boldine enhances bile production in rats via osmotic and farnesoid X receptor dependent mechanisms.

Boldine, the major alkaloid from the Chilean Boldo tree, is used in traditional medicine to support bile production, but evidence to support this function is controversial. We analyzed the choleretic potential of boldine, including its molecular background. The acute- and long-term effects of boldine were evaluated in rats either during intravenous infusion or after 28-day oral treatment. Infusion of boldine instantly increased the bile flow 1.4-fold in healthy rats as well as in animals with Mrp2 deficiency or ethinylestradiol induced cholestasis. This effect was not associated with a corresponding increase in bile acid or glutathione biliary excretion, indicating that the effect is not related to stimulation of either bile acid dependent or independent mechanisms of bile formation and points to the osmotic activity of boldine itself. We subsequently analyzed bile production under conditions of changing biliary excretion of boldine after bolus intravenous administration and found strong correlations between both parameters. HPLC analysis showed that bile concentrations of boldine above 10 µM were required for induction of choleresis. Importantly, long-term pretreatment, when the bile collection study was performed 24-h after the last administration of boldine, also accelerated bile formation despite undetectable levels of the compound in bile. The effect paralleled upregulation of the Bsep transporter and increased biliary clearance of its substrates, bile acids. We consequently confirmed the ability of boldine to stimulate the Bsep transcriptional regulator, FXR receptor. In conclusion, our study clarified the mechanisms and circumstances surrounding the choleretic activity of boldine.

Cholestatic hepatitis due to Ecballium elaterium ingestion.

Ecballium elaterium is an herbaceous plant belonging to the Cucurbitaceae family. This plant is fairly common in the Mediterranean regions. It is frequently consumed in infusion, mixture of fruit or even in aerosol in cases of fever or flu. This plant is known for its respiratory and ocular toxicity. Hepatotoxicity has never been described in the literature. We report a case of acute cholestatic hepatitis due to Ecballium elaterium in a 39 years old patient, with no past medical history.

Dietary hyodeoxycholic acid exerts hypolipidemic effects by reducing farnesoid X receptor antagonist bile acids in mouse enterohepatic tissues.

Mice were fed a control diet or a diet supplemented with hyodeoxycholic acid, the most abundant bile acid contained in pig bile, for 4 weeks, after which their serum and livers were collected. The contents of total fatty acids of serum and liver cholesteryl esters, and of liver triglycerides, were reduced following the administration of the hyodeoxycholic acid-supplemented diet, which was mainly due to the reductions in the contents of monounsaturated fatty acids. Free cholesterol contents in the serum and liver were not changed by hyodeoxycholic acid administration. Hyodeoxycholic acid administration reduced the gene expression levels of sterol regulatory element binding protein 1c, acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase-1. Hyodeoxycholic acid administration markedly changes the ratio of FXR-antagonist/FXR-agonist bile acids in the enterohepatic tissues of the mice (1.13 and 7.60 in hyodeoxycholic acid and control diet groups, respectively). Our findings demonstrate that hyodeoxycholic acid administration exerts the hypolipidemic effect in mice, in which downregulations of de novo lipogenesis and desaturation of saturated fatty acids are suggested to play important roles. In addition, regulation of FXR activation through the selective modification of the enterohepatic bile acid pool may be involved in the hypolipidemic effect of hyodeoxycholic acid administration.

[The choleretic and hepatoprotective effect of Hypecoum erectum extract].

The choleretic and hepatoprotective effect of Hypecoum erectum L. dry extract on toxic hepatitis was studied. Experimental hepatitis was caused by the introduction of D-galactosamine to Wistar white rats in the dose of 500 mg/kg of the animal weight once a day for 3 days. The H. erectum extract was administered per os in the dose of 50 mg/kg for 7 days. It has been established that H. erectum extract has a marked hepatoprotective effect in the case of D-galactosamine hepatitis in white rats that is characterized by inhibition of the disturbances in cholate-synthetic functions of the liver, increase of bile secretion rate, preservation of cholate concentration in the bile. The tested remedy diminishes dystrophic and necrotic processes, decreases the intensity of inflammatory infiltration in the liver and stimulates regeneration of liver cells in D-galactosamine hepatitis.

[Beneficial effects of preoperative administration of Inchinkoto in patients undergoing major hepatectomy].

Inchinkoto (ICKT) is one of the most commonly used herbal medicines and is a hepatoprotective agent. Among the numerous chemical compounds included in ICKT, geniposide is the most abundant component. After oral intake, geniposide is converted into the active metabolite genipin by intestinal bacteria and absorbed in the portal circulation. The biological properties of ICKT and its major active ingredient genipin have been studied in numerous experiments using cells and animals. ICKT or genipin administration exerts a choleretic effect through upregulation of multidrug resistance-associated protein 2 in hepatocytes. ICKT also exerts antiapoptoic activity by inhibiting the transforming growth factor beta 1- or tumor necrosis factor alpha-dependent signaling pathway. The excessive inflammatory response induced by various forms of hepatic stress is also attenuated by ICKT preadministration. Proinflammatory cytokine-induced upregulation of inducible nitric oxide synthase is strongly attenuated by ICKT in both in vivo and in vitro experiments. Moreover, ICKT enhances antioxidant enzymes in the liver under oxidative stress. These experimental results clearly indicate the effects of ICKT on hepatic stress. To date, however, clinical data on the benefits of ICKT for liver disease are very rare. To extend the clinical applications of ICKT in humans, it is crucial to design and perform a rigorous clinical trial. In this review article, recent evidence relating to the hepatoprotective effects of ICKT in the field of basic and clinical science is summarized and discussed.

Artemisia capillaris extract protects against bile duct ligation-induced liver fibrosis in rats.

Artemisia capillaris has been widely used as a traditional herbal medicine in the treatment of liver diseases. However, no previous study has investigated whether A. capillaries alone is effective in treating pathological conditions associated with cholestatic liver injury. In the present study, we evaluated the anti-hepatofibrotic effects of A. capillaris (aqueous extract, WAC) in a bile duct ligation (BDL)-induced cholestatic fibrosis model. After BDL, rats were given WAC (25 or 50 mg/kg) or urosodeoxycholic acid (UDCA, 25 mg/kg) orally for 2 weeks (once per day). The serum cholestatic markers, malondialdehyde, and liver hydroxyproline levels were drastically increased in the BDL group, while administering WAC significantly reduced these alterations. Administering WAC also restored the BDL-induced depletion of glutathione content and glutathione peroxidase activity. Cholestatic liver injury and collagen deposition were markedly attenuated by WAC treatment, and these changes were paralleled by the significantly suppressed expression of fibrogenic factors, including hepatic alpha-smooth muscle actin (α-SMA), platelet-derived growth factor (PDGF), and transforming growth factor beta (TGF-ß). The beneficial effects of WAC administration are associated with antifibrotic properties via both upregulation of antioxidant activities and downregulation of ECM protein production in the rat BDL model.

Effects of rectal administration of taurocholic acid on glucagon-like peptide-1 and peptide YY secretion in healthy humans.

Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), secreted by enteroendocrine L-cells located most densely in the colon and rectum, are of fundamental importance in blood glucose and appetite regulation. In animal models, colonic administration of bile acids can stimulate GLP-1 and PYY by TGR5 receptor activation. We evaluated the effects of taurocholic acid (TCA), administered as an enema, on plasma GLP-1 and PYY, as well as gastrointestinal sensations in 10 healthy male subjects, and observed that rectal administration of TCA promptly stimulated secretion of both GLP-1 and PYY, and increased fullness, in a dose-dependent manner. These observations confirm that topical application of bile acids to the distal gut may have potential for the management of type 2 diabetes and obesity.

[Comparative evaluation of various methods of conservative therapy of early stage of cholelithiasis].

UNLABELLED: THE AIM OF INVESTIGATION: To explore the possibilities of use of conservative therapy in the early stage of cholelithiasis. MATERIALS AND METHODS: In the treatment of patients with early stage of gallstone disease in 103 patients was used mineral water Uvinskaya, in 96--Ursosan and in 118--Ursosan combined with mineral water Uvinskaya. RESULTS: The comparative evaluation of different variants of therapy showed that combined use of Ursosan and mineral water Uvinsky was the most effective to eliminate the clinical symptoms of the disease and reduce the lithogenic properties of bile.

[Innovations in the diagnosis and treatment of cholelithiasis].

AIM: To determine the density of densitometric gallstones and biliary sludge in order to clarify the possibility of lithotherapy in patients with gallstone disease (GSD). MATERIALS AND METHODS: 70 patients were carried out a comprehensive clinical examination with determination of densitometric density of gallstones and/or biliary sludge by means of computer tomography (CT), ultrasound of the abdomen, biochemical blood analysis. Assigned to the complex lithotherapy (Ursofalk and Kholit) in standard dosages, the results were evaluated in a year. RESULT: It was found that the density of bile in patients with GSD was ranging from +4 to +10 HU, sludge - +17,5 HU, gall stones - over +20 HU. The main factor of the exoediency of conservative therapy of GSD is to determine the density of gallstone by CT, which should not exceed +54 HU (+29,6 +/- 3,4 HU). Visualization of stones on CT is much higher (30%) than in Rg (10%), and its density is observed at more than +75,0 HU. Sludge particle less than 2.0 mm, but having a density more than +20,0 HU, should be viewed as a gallstone. Kholit, a herbal medicine, improves functional and structural indicators of biliary tract, digestive processes of cavity, and may be recommended as a monotherapy in stage I of GSD, as well as a component of combination therapy of cholelithiasis.

High-dose ursodeoxycholic acid increases risk of adverse outcomes in patients with early stage primary sclerosing cholangitis.

BACKGROUND: Ursodeoxycholic acid (UDCA) in a dose of 28-30 mg/kg/day increases the likelihood of clinical deterioration of primary sclerosing cholangitis (PSC) patients. AIM: To compare the risk of adverse clinical endpoints in patients with varying disease status. METHODS: We reviewed records from patients previously enrolled in a study evaluating the effects of high dose (28-30 mg/kg/day) UDCA in PSC. Patients were grouped according to treatment (UDCA vs. placebo) and baseline disease status (histological stage of PSC, total serum bilirubin). Development of clinical endpoints including death, liver transplantation, cirrhosis, oesophageal varices and cholangiocarcinoma was sought. RESULTS: A total of 150 patients were included of whom 49 patients developed endpoints. There was an increased development of endpoints among patients using UDCA vs. placebo (14 vs. 4, P=0.0151) with early histological disease (stage 1-2, n=88) but not with late stage (stage 3-4, n=62) disease (17 vs. 14, P=0.2031). Occurrence of clinical endpoints was also higher in patients receiving UDCA vs. placebo (16 vs. 2, P=0.0008) with normal bilirubin levels (total bilirubin ≤1.0 mg/dL) but not in patients with elevated bilirubin levels (15 vs. 16, P=0.6018). Among patients not reaching endpoints 31.7% had normalisation of their alkaline phosphatase levels when compared to 14.3% in patients who reached endpoints (P=0.073). CONCLUSION: The increased risk of adverse events with UDCA treatment when compared with placebo is only apparent in patients with early histological stage disease or normal total bilirubin.

Early morbidity encountered in the dietary-related mouse model of Barrett's esophagus: a question of zinc?

Recently, a mouse model for Barrett's esophagus based on a zinc-deficient diet supplemented with deoxycholic bile acids has been published. The aim of this study was to attempt to reproduce these data and extend them by employing genetically modified mice and intraperitoneal iron supplementation. The study design encompassed six experimental groups (wild type, Apc-mutant and Smad4-mutant mice, with or without iron injections), with all animals fed with the zinc-deficient diet supplemented with deoxycholic bile acids. All treatments were started at 3-5 weeks of age (the majority [78%] at 5 weeks). Animals were scheduled for euthanasia at two distinct time points, namely at 3 and 6 months of age. All mice showed signs of considerable distress already 4 weeks after the start of the modified diets, and had to be euthanized before the first evaluation time point (mean age 9.3 weeks, range 5-15 weeks). No differences were observed between wild type and genetically modified mice, or between animals with or without iron supplementation. On histological examination, we could not detect any lesions (Barrett's esophagus-like or tumors) other than esophagitis. In the currently presented experimental settings, we were not able to reproduce the mouse model according to which Barrett's-like lesions could be detected in animals fed with the zinc-deficient diet supplemented with deoxycholic bile acids.

Dietary bile acid supplementation improves intestinal integrity and survival in a murine model.

PURPOSE: In vitro supplementation of the bile salt, taurodeoxycholic acid (TDCA), has been shown to stimulate proliferation and prevent intestinal apoptosis in IEC-6 cells. We hypothesize that addition of TDCA to a rodent liquid diet will be protective against induced intestinal injury. METHODS: C57Bl6 mice were fed a liquid diet with or without 50-mg/(kg d) TDCA supplementation. After 6 days, the mice were injected with lipopolysaccharide (LPS) (10 mg/kg) to induce intestinal injury. Specimens were obtained 24 hours later and evaluated for intestinal apoptosis, crypt proliferation, and villus length. A separate cohort of animals was injected with LPS (25 mg/kg) and followed 7 days for survival. RESULTS: Mice whose diet was supplemented with TDCA had significantly increased survival. After LPS-induced injury, mice supplemented with TDCA showed decreased intestinal apoptosis by both H&E and caspase-3. They also had increased intestinal proliferation by 5-bromo-2'deoxyuridine staining and increased villus length. CONCLUSIONS: Dietary TDCA supplementation alleviates mucosal damage and improves survival after LPS-induced intestinal injury. Taurodeoxycholic acid is protective of the intestinal mucosa by increasing resistance to injury-induced apoptosis, stimulating enterocyte proliferation, and increasing villus length. Taurodeoxycholic acid supplementation also results in an increased survival benefit. Therefore, bile acid supplementation may potentially protect the intestine from injury or infection.

Extracts from the Mongolian traditional medicinal plants Dianthus versicolorFisch. and Lilium pumilum Delile stimulate bile flow in an isolated perfused rat liver model.

AIM OF THE STUDY: Dianthus versicolor (Caryophyllaceae) and Lilium pumilum (Liliaceae) are two medicinal plants used in traditional Mongolian medicine to treat hepatic and gastrointestinal disorders. In this study aqueous (AE) and methanolic (ME) extracts of Dianthus versicolor and Lilium pumilum were investigated for their influence on the bile flow. The aqueous extracts of both plants were tested in absence and presence of 10 µM taurocholic acid at three different concentrations (100, 250, and 500 mg/L). The aqueous extract of Dianthus versicolor was further purified in order to locate the active principles. Two resulting fractions, one enriched in flavonoids and the other in sugars, were investigated for their influence on the bile flow in absence of taurocholic acid at 10, 20, and 40 mg/L. The aqueous extracts of both plants were analysed qualitatively by LC-MS(n) and quantitatively by UV-spectrophotometry. MATERIALS AND METHODS: The bile flow experiments were performed in the isolated perfused rat liver. The compounds were identified by LC-DAD-MS(n) and TLC using references. The UV-spectrophotometric analysis was based on the monograph "Passiflorae herba" of the European Pharmacopoeia, and the total flavonoid contents were calculated and expressed as vitexin. RESULTS: AE and ME of both plants increased the bile flow dose-dependently (between 9% and 30%), and no hepatotoxic effect was seen even during longer perfusions. Stimulation of bile secretion was comparable in the presence and in the absence of taurocholic acid. The flavonoid fraction of Dianthus versicolor increased the bile flow by 18% (p<0.05) at 40 mg/L, which was comparable to the positive control cynarin. The phytochemical investigations of the Dianthus versicolor AE (total flavonoid content 1.78%) revealed the presence of the isovitexin derivative saponarin. In the AE of Lilium pumilum (total flavonoid content 1.04%) the flavonoids rutoside, kaempferol-3-O-rutinoside, and isorhamnetin-3-O-rutinoside were detected. CONCLUSIONS: The results show that choleresis under extract application is due to a stimulation of the bile-salt-independent bile flow which might be caused by the osmotic power of the extracts (hydrocholeresis). The flavonoids seem to contribute to the bile-flow-stimulating effect of Dianthus versicolor. Both plants exhibit a considerable choleretic effect that contributes to their use in traditional Mongolian medicine against gastrointestinal disorders.

Effects of Japanese herbal medicine Inchin-ko-to on endotoxin-induced cholestasis in the rat.

BACKGROUND/OBJECTIVE: Inchin-ko-to (ICKT) is an herbal medicine used in Japan to treat jaundice and liver fibrosis.We investigated the effect of oral ICKT supplementation on endotoxin-induced cholestasis in the rat. MATERIAL AND METHODS: Lipopolysaccharide (LPS) injection (1 mg/kg body weight i.p.) was used as a model of sepsis-induced cholestasis. Bile flow, biliary bile salt secretion, biliary glutathione secretion and protein expression of the main hepatobiliary transporters Na(+)-taurocholate-cotransporting peptide (Ntcp), multidrug resistance protein 2 (Mrp2) and bile salt export pump (Bsep) were analyzed by conventional techniques in ICKT treated and non-treated animals. RESULTS: Injection of LPS induced a significant decrease of bile flow (-24%), biliary bile salts (-40%) and glutathione excretion (-70%) as well as a significant decrease in Ntcp (-90%) and Mrp2 (-80%) protein levels. ICKT supplementation partially prevented the effects of LPS determining a less intense reduction in bile flow (-10%), a normalization of glutathione excretion as well as a significant increase in Mrp2 protein levels to 60% of the levels observed in control animals. ICKT administration did not modify the effects of LPS on BS secretion or Ntcp protein levels. CONCLUSION: Our data show that oral supplementation of ICKT partially prevents LPS-induced cholestasis by increasing Mrp2 protein levels and biliary glutathione excretion thus increasing bile salt-independent flow.

[Effect of plant extracts from Baikal region on the choleretic reaction in white rats].

In the given work was estimated the choleretic activity of the extracts that was derived from the plants of the Baikal region. It had been shown that the experimental-therapeutic doses of the extracts stimulate choleretic reaction in intact rats.

Choleretic effects of the Mongolian medicinal plant Saussurea amara in the isolated perfused rat liver.

Saussurea amara is used in traditional Mongolian medicine for the treatment of hepato-biliary disorders. To determine the plant's effect on the bile-salt independent bile flow (hydrocholeresis) as a measure of liver exocrine functions, different extracts were investigated in the isolated rat liver perfusion system. The methanolic extract (3) exerted a dose-dependent increase in bile flow (16%, 37%, 53%, 61%) in concentrations of 50 mg/L, 100 mg/L, 250 mg/L and 500 mg/L. The aqueous crude extract (1) and the ethyl acetate extract (2) also showed a dose-dependent increase, whereas at the highest concentrations (1000 mg/L and 100 mg/L, respectively) a continuous decrease in bile flow could be observed. Cynaropicrin also provoked a dose-dependent increase in bile flow, but caused liver damage at the highest dose tested (20 mg/L). Apigenin 7- O-glucoside, present in extracts 2 and 3, induced a dose-dependent increase of 20%, 30% and 40% (5 mg/L, 10 mg/L, 20 mg/L) and showed a significantly higher effect than the reference substance cynarin. The total flavonoid content was determined by spectrophotometry. To quantify the absolute amount of cynaropicrin in the crude drug and in the tested extracts, an HLPC system was established with santonin as internal standard.