Choleretic Properties Research Articles

Known and unknown hymecromone. A review

Hymecromone (4-MU) is a recognized agent currently used in clinical practice. Since 1960, hymecromone has been used in many countries as a choleretic and cholespasmolytic, a drug approved for use in humans with biliary tract disorders. The review presents both traditional European and Russian studies of the selective antispasmodic and choleretic properties of hymecromone, due to which hymecromone is the drug of choice for the treatment of biliary tract diseases, as well as new fundamental and clinical studies of numerous pleiotropic effects of 4-MU associated with inhibition of hyaluronic acid and many other properties of this exciting molecule. These include antibacterial, antiviral, and nonspecific anti-inflammatory effects. Positive results have been demonstrated in carbohydrate and lipid metabolism disorders, autoimmune diseases, as well as liver, heart, and kidney diseases. Numerous in vitro and in vivo studies have been presented in pancreatic, prostate, skin, esophagus, breast, liver, ovary, bone cancers, metastatic lesions, leukemia, autoimmune and inflammatory diseases. Hymecromone is indicated not only as a choleretic and cholespasmolytic but also as a choleseptic in cholangitis and chronic cholecystitis, including opisthorchiasis, which does not disagree with its label. Odecromone® (hymecromone, tablets 200 mg) is available on the Russian market; it replaced the originator drug and is its fully equivalent generic.

The Potential of Herbal Management in Gallstone (Pittashmari) – A Case Study

In India, cholelithiasis (gallstones) is now the leading problem. Some patients have a single gallstone, while others develop multiple gallstones at the same time. It could be as big as a golf ball or as small as a grain of sand. The risk factors for gallstones include middle age, inconsistent eating patterns, extended fasting, and metabolic syndrome. Surgical treatment is usually required, such as the removal of the entire gall bladder (cholecystectomy). In Ayurveda, it is not texted directly. There is a description of ashmari (urinary calculi), so by considering the symptoms and pathology of cholelithiasis, it can be correlated with pittashmari, as that site was given for Accha pitta according to the Ayurvedic classics. Pittashamri pathophysiology includes kapha-pitta vitiation and an obstructed Vayu marga (path). A 40-year-old male patient complained of pain in the upper abdomen along with bloating, chest discomfort, and constipation for the past 6 months. The patient had been taking modern medications. But patient experienced only temporary relief of symptoms. So, the patient came to the OPD for Ayurvedic treatment. Investigating with ultrasound, the patient was diagnosed with cholelithiasis and treated purely with herbal drugs as the patient was unaffordable. Pittarechaka (cholagogue), yakruta-pleehaghna, ashmarighna, and drugs with choleretic properties, such as kokilaksha, haritaki, bhumyamalaki, and rohitakarishta, were chosen. Within 15 days, the patient’s symptoms had significantly improved. The Numerical Rating Scale (NRS) was used to assess abdominal pain. A reduction in the size of the gallstone was seen within three months, and a completely normal ultrasound after one year, as discussed here.

CHOLERETIC EFFECT OF THE COMPLEX PLANT SUPPLEMENT IN EXPERIMENTAL LIVER DAMAGE

Relevance. The search for supplements with choleretic activity is of great interest due to their detoxicant properties and possible hepatoprotective ef-fect. The aim of our study was to evaluate choleretic effect of the complex plant supplement comprised of Hypecoum erectum L.; Hedysarum dahuri-cum Turcz. ex B.Fedtsch.; Glycyrrhiza uralensis Fisch. ex DC.; Calendula officinalis L.; Scutellaria baicalensis Georgi. dry extracts. Material and methods. The research was conducted on an animal model of acute liver damage induced by CCl4 in 84 albino Wistar rats. The studied complex plant supplement was researched in doses of 100mg/kg, 200 mg/kg and 300 mg/kg in the course of 14 days starting from the 2nd day of the experiment. Choleretic properties were evaluated by both the speed of bile secretion (mg/min) per 100 g of animal weight and the total amount of bile secreted during four hours of observation. Results. It has been established that the use of the dry extract in tetrachloromethane hepatitis in white rats has a choleretic effect characterized by an increase in the rate of bile secretion, an increase in the amount of discharged bile and the growing concentration of bile acids.

Effect of Kutaki (Picrorhiza Kurroa Royle Ex Benth) on Dyslipidemia

Dyslipidemia is a lifestyle disorder related to a metabolic disorder of lipoprotein metabolism. It is mainly characterizedby raised (TCH) total cholesterol, low-density lipoprotein (LDL) cholesterol, triglyceride (TG) levels, and a fall in the high-densitylipoprotein (HDL) cholesterol levels. It is the key contributing cause of atherosclerosis, coronary artery ailment, andcerebrovascular disease. It can be equated with medodushti and included under Santarpanjanya vyadhi as “Medoroga. This studyassesses the effect of Kutaki (Picrorhiza kurroa Royle ex Benth) on Dyslipidemia. A total of 30 patients with Dyslipidemia weretreated with Kutaki tablets 500 mg twice a day before meals with lukewarm water for 60 days. They were assessed for Lipid levels,Fasting glucose level, AST, ALT, S.Creatinine, and Serum Urea on days 0, 30, and 60. Significant improvement was observed in allparameters after the completion of treatment. Tikta Rasa (bitter taste), Ushna Virya (hot potency), Agnideepan, Pachana, and Lekhanaproperties of Kutaki help break Samprapti. Active ingredients of Kutaki possess Hypolipidemic and choleretic properties, whichhelp correct Lipid levels. Hepatoprotective and nephroprotective properties help in maintaining liver and kidney functionsnormally. It helps in improving deranged Agni and constipation. Kutaki can be useful in treating Dyslipidemia with any side effects.

Effects of ursodeoxycholic acid and glutathione combination in spleen TNF-α and apoptotic index in rats with cholestasis

Background: Cholestasis is a disorder of the formation or flow of bile. Among its contributors, tumour necrosis factor (TNF)-α stands out as the most influential inducer of apoptosis. Meanwhile, ursodeoxycholic acid (UDCA) is a valuable agent with choleretic properties, protecting the hepatobiliary system. Glutathione (GSH) enhances endothelial response and prevents liver fibrosisObjectives: This study evaluates the effect of a combination of GSH-UDCA on splenic TNF-α expression and apoptosis index in Sprague Dawley (SD) rats with cholestasisMethods: This experiment with a post-tests-only control group design involving 28 male SD rats. They were randomly into four groups: group (K) with 20 mg UDCA, group 1 (P1) with 10 mg UDCA + 10 mg GSH, group 2 (P2) was given UDCA 20 mg + GSH 15 mg, and group 3 (P3) was given UDCA 30 mg + GSH 20 mg. Cholestasis was obtained by ligation of the common bile duct through a laparotomy. During three weeks of trial, rats were administered daily with UDCA orally and GSH intramuscularly. On day 22, rats were sacrificed and spleen samples were taken for anatomical pathology examination. Results: There were significant differences in TNF-α expression between groups K vs P3; P1 vs P3, and P2 vs P3 (p=0.002). There was a significant difference in the apoptotic index between groups K vs P1 (p<0.001); K vs P2 (p=0.004), and K vs P3 (p=0.005).Conclusions: The UDCA-GSH combination demonstrated a prophylactic effect in SD rats with cholestasis and might be an effective supplemental therapy with UDCA for cholestatic diseases. The difference in TNF-α expression and apoptotic index was lower in SD rats UDCA-glutathione combination group than single dose UDCA. Between TNF-α and the apoptotic index, there is a moderate positive relation.

Active enterohepatic cycling is not required for the choleretic actions of 24-norUrsodeoxycholic acid in mice.

The pronounced choleretic properties of 24-norUrsodeoxycholic acid (norUDCA) to induce bicarbonate-rich bile secretion have been attributed to its ability to undergo cholehepatic shunting. The goal of this study was to identify the mechanisms underlying the choleretic actions of norUDCA and the role of the bile acid transporters. Here, we show that the apical sodium-dependent bile acid transporter (ASBT), organic solute transporter-α (OSTα), and organic anion transporting polypeptide 1a/1b (OATP1a/1b) transporters are dispensable for the norUDCA stimulation of bile flow and biliary bicarbonate secretion. Chloride channels in biliary epithelial cells provide the driving force for biliary secretion. In mouse large cholangiocytes, norUDCA potently stimulated chloride currents that were blocked by siRNA silencing and pharmacological inhibition of calcium-activated chloride channel transmembrane member 16A (TMEM16A) but unaffected by ASBT inhibition. In agreement, blocking intestinal bile acid reabsorption by coadministration of an ASBT inhibitor or bile acid sequestrant did not impact norUDCA stimulation of bile flow in WT mice. The results indicate that these major bile acid transporters are not directly involved in the absorption, cholehepatic shunting, or choleretic actions of norUDCA. Additionally, the findings support further investigation of the therapeutic synergy between norUDCA and ASBT inhibitors or bile acid sequestrants for cholestatic liver disease.

Anti-inflammatory effect of polyherbal composition with hepatoprotective and choleretic properties on LPS-stimulated murine macrophages.

A polyherbal formulation with hepatoprotective and choleretic properties combining pharmacological potential of eight medicinal plants was developed in Nargiz Medical center (Republic of Azerbaijan) for the use as herbal tea. To explore the effect of polyherbal composition on the metabolism of LPS-stimulated macrophages in vitro. The qualitative and quantitative phytochemical analysis was conducted using specific color reactions and gas chromatography-mass spectrometry (GC-MS). Nitric oxide (NO) assay was determined using the Griess reaction. Reactive oxygen species (ROS) generation was measured using ROS-sensitive fluorescence indicator, H2DCFDA, by flow cytometry. Arginase activity was examined by colorimetric method. The studied polyherbal formulation exerted anti-inflammatory activity in LPS-stimulated macrophages which was evidenced by dose-dependent decrease of ROS generation and by shift of arginine metabolism to the increase of arginase activity and decrease of NO release. Our findings suggest that the herbal tea reduces macrophage inflammatory activity, that provide an important rationale to utilize it for the attenuation of chronic inflammation typical of hepatobiliary disorders.

STUDY OF THE HEPATOTROPIC ACTIVITY OF SAFOROFLAVONOLOSIDE UNDER EXPERIMENTAL CONDITIONS

The effect of the flavonoid glycoside sophoraflavonoloside isolated from the petals of the Crocus sativus L plant (Saffron seed) on hepatoprotective, choleretic and approximate motor activity in chronic liver damage with heliotrin when administered orally at a dose of 100 mg / kg under experimental conditions was studied. The results obtained on the basis of the conducted studies were compared with the control group and the most active dose of the comparative drug Karsil at a dose of 50 mg/kg. Based on preliminary research results, it was found that Soforaflavonoloside does not lag behind karsil and even slightly surpasses a comparable drug in hepatoprotective and choleretic properties. This suggests that the substance under study requires a more extensive in-depth study of the effect of sophoraflavonoloside on the normal and impaired functioning of the liver.

ФЛАВОНОИДЫ И ИЗОФЛАВОНОИДЫ РАСТЕНИЙ РОДА TRIFOLIUM L. СТРУКТУРНОЕ РАЗНООБРАЗИЕ И БИОЛОГИЧЕСКАЯ АКТИВНОСТЬ

The review presents data on the use in traditional medicine, the chemical composition, degree of knowledge, structural diversity and biological activity of flavonoids and isoflavones of the genus Trifolium L. world flora. Many species of clover are widely used in folk medicine for asthma, shortness of breath, cough, dysentery, pulmonary tuberculosis, metabolic diseases and kidney stones, kidney disease. On the basis of clover extracts meadow (T. pratense L.), a number of dietary supplements with a wide range of pharmacological effects. The information on the composition of flavonoids and isoflavones species of Trifolium, the distribution in plants, structure and sources produce 176 compounds. Flavonoids and isoflavones genus Trifolium possess cholesterol-lowering, choleretic, antizotemition, diuretic, estrogenic and antioxidant properties. Species Trifolium are promising for further phytochemical study and development of new effective drugs. Cited in the survey data can be used to address issues chemosystematics plants of the genus Trifolium L.

English

Cynara scolymus L. leaves, popularly known as globe artichoke, have cholagogue and choleretic properties which are attributed to caffeoylquinic acid derivatives. Although, there are already pharmacopoeial methods for quality control of artichoke dry leaf extract, it only shows the assessment of chlorogenic acid determination. This study aimed to adapt and validate a method for simultaneous determination of neochlorogenic, chlorogenic, cryptochlorogenic, cynarin and isochlorogenic acids A and C in tablets or capsules of globe artichoke leaf extract herbal medicines. Also, it evaluated the content of these caffeoylquinic acid derivatives in three commercial products and leaf extract. The validation considered the parameters of selectivity, precision, linearity, quantification and detection limits and accuracy. The method proved to be selective, precise and accurate. Commercial products and leaf extract had significantly different concentrations of standard compounds which may bring an impact on therapeutic outcomes. The method proposed was suitable for the identification and quantification of caffeoylquinic acid derivatives in tablets and capsules and could be used in quality control, ensuring the safety and efficacy of commercially prepared herbal medicines. Key words: Herbal medicines, quality control, Cynara scolymus.

α5β1 integrins act as sensors for tauroursodeoxycholic acid in hepatocytes

Ursodeoxycholic acid, which in vivo is converted to its taurine conjugate tauroursodeoxycholic acid (TUDC), is a mainstay for the treatment of cholestatic liver disease. Earlier work showed that TUDC exerts its choleretic properties in the perfused rat liver in a α5β1 integrin-mediated way (Häussinger et al., Gastroenterology, 2003). However, the molecular basis of TUDC-sensing in the liver is unknown.

Globe artichoke as a functional food

Globe artichoke (Cynara cardunculus var. scolymus L. Fiori) is a traditional component of the Mediterranean diet. Artichoke edible parts are one of the richest dietary sources of polyphenols with high bioavailability, and contain also high-quality inulin, fibres and minerals. Moreover, pharmaceutical artichoke leaf extracts show hypocholesterolemic and choleretic properties. Several clinical studies have shown that the bioactive properties of globe artichoke are due to the high content of polyphenolic compounds in flower heads and leaves, in particular hydroxycinnamates and flavonoids. The total antioxidant capacity of artichoke flower heads is one of the highest reported for vegetables, and is strictly related to their polyphenolic content. Different agronomic variables, such as mycorrhizal inoculation, may affect plant secondary metabolism, and in particular the production of metabolites with health-promoting activities. Our recent data showed large increases of total phenolic content and antioxidant activity in leaves and flower heads of mycorrhizal artichoke plants.

Ursodeoxycholic acid action on the transport function of the small intestine in normal and cystic fibrosis mice.

Ursodeoxycholic acid possesses choleretic and cytoprotective properties and in cystic fibrosis (CF) it is used to treat the hepatobiliary symptoms of the disease. This study investigated the effects of this bile acid on the transport function of the small intestine in normal and CF mice. The effects of ursodeoxycholic acid were monitored as changes in short-circuit current (SCC) in stripped sheets of small intestine from normal (Swiss MF1) and transgenic CF (Cftr(tm2Cam)) mice. In ileal sheets from Swiss MF1 mice, mucosal ursodeoxycholic acid caused a biphasic increase in SCC. The first phase was reduced by lowering the mucosal Na+ concentration, while the second phase was inhibited by (Cl-)-free conditions, serosal furosemide or mucosal diphenylamine-2-carboxylic acid (DPC), suggesting an initial Na+-dependent bile acid absorption followed by a stimulation of electrogenic Cl- secretion. Serosal application of ursodeoxycholic acid to the ileum and mucosal or serosal application to the mid-intestine and jejunum elicited a secretory response only. Secretion was Ca2+-dependent, but did not involve neural mechanisms. Mucosal mast cells, histamine and serotonin (5-HT) were implicated in the secretory response. Responses in tissues from transgenic wild-type mice were similar to those obtained with Swiss MF1 mice, but the secretory response to mucosal or serosal application of the bile acid was impaired in CF tissues. In ilea from CF mice the initial absorptive phase of the response to mucosal ursodeoxycholic acid was still observed. It is concluded that ursodeoxycholic acid induces secretion throughout the murine small intestine by a mechanism that involves degranulation of mucosal mast cells. In the ileum Na+-dependent absorption can also be detected. The secretory response is defective in CF intestine, but the absorptive effect is still present.

Antioxidant and Choleretic Properties ofRaphanus sativusL. Sprout (Kaiware Daikon) Extract

Brassica vegetables and glucosinolates contained therein are supposed to reduce the risk of cancer and to possess health-promoting properties. The benefits of a Brassica-based diet may be particularly expressed by eating sprouts, in which the glucosinolate content is higher than in mature vegetables. With this in mind, a first objective of this study was to evaluate the antioxidant properties of radish (Raphanus sativus L.) sprouts (Kaiware Daikon) extract (KDE), in which the glucosinolate glucoraphasatin (GRH), showing some antioxidant activity, is present at 10.5% w/w. The contribution of GRH to KDE's antioxidant activity was considered in two chemical assays (Trolox equivalent antioxidant capacity and Briggs-Rauscher methods). The total phenol assay by Folin-Ciocalteu reagent was performed to quantify the reducing capacity of KDE. Finally, on the basis of the putative choleretic properties of antioxidant plant extracts, the effect on the bile flow of KDE administration was investigated in an animal experimental model. The findings showed that KDE has antioxidant properties and significantly induced bile flow in rats administered 1.5 g/kg of body weight for 4 consecutive days.

Effect of Picroliv on cadmium-induced hepatic and renal damage in the rat

The therapeutic efficacy of Picroliv--a standardized extract of Picrorhiza kurroa--was investigated in male rats exposed to CdCl2 (0.5 mg/kg, sc), 5 days/week for 18 weeks. Picroliv at two doses (6 and 12 mg/kg, po) was given to the cadmium (Cd)-administered group for the last 4 weeks (i.e., weeks 15-18). The Cd altered oxidative stress indices, such as increased lipid peroxidation and membrane fluidity, reduced levels of non-protein sulphydryls (NPSHs), and Na+K+ATPase activity in the liver and kidney were found close to the control values by Picroliv treatment, suggesting its antioxidant potential. The hepatoprotective action of Picroliv was evident by its ability to lower the Cd-induced liver function parameters--the serum enzymes, such as alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT) and lactate dehydrogenase (LDH). Bile flow and biliary Cd also increased as a result of Picroliv's choleretic property. The Cd-induced serum urea and urinary excretion of proteins, calcium (Ca), Cd and enzymes, such as N-acetyl-beta-D-glucosaminidase (NAG) and LDH, were less marked on Picroliv treatment, indicating recovery from nephrotoxicity. Organ uptake of Cd and essential metals by Cd exposure was reduced on Picroliv treatment. Cd-induced hepatic metallothionein (MT) was lowered by Picroliv, whereas renal MT was unaltered. Cd-induced hepatic damage was also minimized. However, the renal morphological changes were marginally protected by Picroliv. The 12-mg Picroliv dose was more effective than the 6-mg dose in causing amelioration of the above parameters. This study has provided clear evidence for the hepato- and renal protective efficacy of Picroliv against experimental Cd toxicity.

ESSENTIAL OILS FROM THREE CURCUMA SPECIES COLLECTED IN THAILAND

ESSENTIAL OILS FROM THREE CURCUMA SPECIES COLLECTED IN THAILAND

Extrahepatic biliary obstruction: can silymarin protect liver function?

The hepatoprotective property of silymarin is well known. However, it is not known whether the antioxidant silymarin might have a beneficial effect in extrahepatic cholestasis in common bile duct ligated rats. Malonaldehyde property concentrations, the hydrogen-donating ability and reducing power were measured in liver homogenates by spectrophotometry, as well as free SH-group levels and glutathione-reductase activities in sera. The total scavenger capacity of the livers was quantified by a chemiluminometric method. The elevated lipid peroxidation and decreased antioxidant capacity of liver homogenates and sera could be observed in ligated rats. Silymarin pretreatment improved the antioxidant capacity of the liver, diminished the direct bilirubin concentration and caused an increase of liver enzyme activities compared with the groups without treatment. These effects of silymarin suggest that it may be a useful agent for improving the antioxidant defensive system in extrahepatic cholestasis, but its choleretic property should be considered.

Role of perivenous hepatocytes in taurolithocholate-induced cholestasis in vivo

The magnitude of cholestasis induced by taurolithocholic acid (TLCA) and its relationship with phase I metabolism were analyzed in rats treated with bromobenzene (BZ), a chemical that causes selective necrosis of perivenous (zone 3) hepatocytes. Forty-eight hours after BZ administration (600 mg/Kg bw), a single dose of 20 μmol/Kg bw of TLCA was injected. Bile was collected during 180 min and bile flow and total bile acid excretion rate were determined. Biliary bile acid composition was analyzed by gas–liquid chromatography-mass spectrometry. BZ administration did not affect the development of TLCA-induced cholestasis, but exacerbated the bile acid-induced decrease in bile flow during the period of recovery from cholestasis. Biliary excretion of total bile acids after TLCA injection relative to basal value was not effected by BZ. The analysis of bile acid composition in bile revealed that TLCA was partially converted to hyodeoxycholic and muricholic acids. The cumulative excretion of all exogenous bile acids and their contribution to the composition of the biliary bile acid pool were not substantially affected by zone 3 necrosis, suggesting that synthesis and secretion of hydroxylated derivatives of TLCA were maintained by zone 1 and 2 hepatocytes. The relative content of endogenous bile acids was not affected by BZ during TLCA-induced cholestasis. Thus, it seems unlikely that the exacerbation of the cholestasis in BZ-treated rats is due to different choleretic properties and/or toxicity of the bile acid pool.

The in vitro effect of dandelions antioxidants on microsomal lipid peroxidation.

Dandelions have long been used in herbal medicine for their choleretic, diuretic, antiinflammatory, appetite-stimulating and laxative properties. An antioxidant property can be supposed as a basis of their-therapeutic effects. To understand the mechanism of the drug's action, the effects of natural extracts on a microsomal fraction of rat liver were examined. The extracts diminished the enzymatically induced-lipid peroxidation and reduced the cytochrome c with and without NADPH in a concentration dependent manner.

Fluorescent bile acid derivatives: Relationship between chemical structure and hepatic and intestinal transport in the rat.

Studies were performed to characterize hepatic and intestinal transport, as well as biotransformation during transport, of a spectrum of fluorescent bile acids containing a fluorophore attached to the side chain. The following two classes of compounds were studied: 1) aminofluorescein (amF) coupled directly to the carboxylic group of a bile acid which was cholic, ursodeoxycholic, or cholylglycine; and 2) nitrobenzoxadiazolyl (NBD) coupled to the ϵ-amino group of a lysine conjugated bile acid, which was cholic or ursodeoxycholic. Fluorescein, a cholephilic organic anion, was studied as a control. Fluorescent bile acids were synthesized and their structures confirmed by nuclear magnetic resonance and mass spectrometry. Using the biliary fistula rat, hepatic transport, biotransformation, and choleretic activity were defined; intestinal absorption was assessed by jejunal or ileal perfusion studies. All fluorescent bile acids had hepatic transport maxima about one-sixth that reported for cholyltaurine, but derivatives of cholylglycine were transported best. Bile acids underwent little (<5%) biotransformation during hepatocyte transport. Only the amF conjugate of cholylglycine had normal choleretic activity; other compounds were hypocholeretic or cholestatic. In contrast, fluorescein was well transported, was partly glucuronidated, and had normal choleretic activity. NBD-tagged, but not amF-tagged, bile acids were actively transported by the intestine (ileum > jejunum), and no fluorescent bile acid had passive intestinal permeability; NBD-tagged bile acids were biotransformed during intestinal transport (jejunum > ileum). We conclude that the structure of the fluorophore as well as that of the bile acid influences transport by the hepatocyte and enterocyte. These fluorescent bile acids differ from fluorescein in being impermeable to cell membranes and undergoing little biotransformation during hepatocyte transport. Of these fluorescent bile acids, cholylglycylamF has hepatocyte transport and choleretic properties most closely resembling those of a natural bile acid. (Hepatology 1997 Nov;26(5):1263-71)