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‘Jurubeba’ (Solanum paniculatum L.) is a medicinal plant used in traditional medicine for liver problems, in addition to being used as a cholagogue, emmenagogue, healing agent, febrifuge, anti-inflammatory, antipyretic, tonic, decongestant, diuretic and against inappetence. Thus, the objective of this study was to evaluate the antioxidant activity, concentration of phenolic compounds and total alkaloids of aqueous extracts prepared from ‘Jurubeba’ leaves subjected to drying. ‘Jurubeba’ leaves were dried at different temperatures (40, 50, 60 and 70 °C) and velocities (0.4 and 0.8 m s-1) of the drying air. Aqueous extracts of the leaves, subjected to drying, were evaluated by absorbance reading in a spectrophotometer. Increase in drying air temperature reduced the contents of total phenolics and total alkaloids of the leaf aqueous extracts, whereas increment in air velocity increased the concentration of these substances. Antioxidant activity was not influenced by the increase in air temperature at air velocity of 0.4 m s-1, but under air velocity of 0.8 m s-1 there was reduction with increasing temperature. Drying of ‘Jurubeba’ leaves can be carried out with temperature of 40 or 50 °C and drying air velocity of 0.4 m s-1. RESUMO A jurubeba (Solanum paniculatum L.) é uma planta usada na medicina tradicional, para problemas hepáticos, além de ser empregada como colagoga, emenagoga, cicatrizante, febrífuga, anti-inflamatória, antipirética, tônica, descongestionante, diurética e na inapetência. Assim, objetivou-se com o presente estudo avaliar a atividade antioxidante, os teores de compostos fenólicos e de alcaloides totais dos extratos aquosos preparados a partir de folhas de jurubeba submetidas à secagem. As folhas de jurubeba foram secas em diferentes temperaturas (40, 50, 60 e 70 °C) e velocidades (0,4 e 0,8 m s-1) do ar de secagem. Os extratos aquosos das folhas, submetidas a secagem, foram avaliados por meio de leitura de absorbância em espectrofotômetro. O aumento da temperatura do ar de secagem reduziu o teor de compostos fenólicos e alcaloides totais dos extratos aquosos das folhas, enquanto que o aumento da velocidade do ar aumentou o teor dessas substâncias, já a atividade antioxidante não foi influenciada pelo incremento da temperatura do ar na velocidade de 0,4 m s-1, mas sob a velocidade do ar de 0,8 m s-1 houve redução com o aumento da temperatura. A secagem das folhas de jurubeba pode ser realizada com temperatura de 40 ou 50 °C e velocidade do ar de secagem de 0,4 m s-1.

Cichorium Intybus L. is a medicinally important plant that belongs to the family Asteraceae. The plant root is used as anti-hepatotoxic, antiulcerogenic, antiinflammatory, appetizer, digestive, stomachic, liver tonic, cholagogue, cardiotonic, depurative, diuretic, emmenagogue, febrifuge, alexeteric and also as tonic. The present study was carried to screen the anxiolytic potential of Cichorium Intybus L methanolic root extracts by using different animal models like actophotometer, rotarod, staircase, holeboard, elevated plus maze tests . In the experiment the extracts found to decrease the anticipatory anxiety of the animal without significant alteration in motor coordination. Efficacy may be attributed to the presence of different phytochemicals like coumarins, flavonoids in the extracts.

Background Botanical pesticide plays an essential role in the control of agricultural pests. Corydalis curviflora Maxim. is used as a cholagogue and larvicide in the rural areas of Northwest China. In this study, our objective was to identify the insect active ingredients of C. curviflora extract. Results Bioassay-guided isolation of the high active fraction led to the identification of two novel N-demethyl hexahydrobenzophenanthridine-type alkaloids, Curviflorain A (1) and Curviflorain B (2), together with nine known alkaloids, ambiguanine A (3), ambiguanine B (4), ambiguanine C (5), 6-acetylambinine (6), 1,1-dimethyl-6-methoxy-7-hydroxyl-1,2,3,4-tetrahydroisoquinoline (7), hendersine B (8), coryximine (9), isochotensine (10) and corysolidine (11). Compounds 1, 2, and 6 showed promising activity to the larvae of Culex pipiens pallens Coq. and Aedes albopictus Skuse. These compounds were also tested against the insect pests, Mythimna separata walker. and Schizaphis graminum Rondani. Conclusion These findings provide a better understanding of the insecticidal activity of C. curviflora extract and the active compounds. This has the potential to lead to a more effective botanical insecticide.

The article has studied and analyzed numerous publications reflecting the results of studies on the physiological effects of artichoke extracts and the use of drugs on its basis in obstetric practice. The structural components of the artichoke are considered, the role of polyphenolic compounds, bioflavonoids, inulin, macro- and microelements in the biochemical processes of the organism is analyzed. Physiological effects of artichoke components were studied in detail. It is shown that they are not only antioxidant, but also hypocholesterolemic, membrane stabilizing, anti-inflammatory, antitumor, immunomodulating, etc. Artichokes have a great preventive potential for increasing the elimination functions of the liver and kidneys, a high antioxidant resource. The multicomponent composition of artichoke extracts determines the versatile effect of the preparations synthesized on their basis. An important feature of artichoke preparations is safety of use, the possibility of using without age restrictions, as well as in children and during pregnancy. The only contraindication for the appointment of an extracts of artichoke is the obstruction of the biliary tract. Particular attention is paid to the mechanisms of hepatoprotective and cholagogue effects of artichoke extracts. From the standpoint of evidence-based medicine, questions of the use of artichoke medications for gestosis, placental insufficiency, and conditions complicating the health of a pregnant woman are covered. In particular, the artichoke extract improves the state of chronic diseases of the gastrointestinal tract in pregnant women, reduces the severity of asthenic syndrome, improves fat metabolism, promotes the restoration of vitamin balance, protects the liver and kidneys from the effects of drugs used to relieve vomiting, increases the level of albumin, reduces bilirubin levels. In dermatosis of pregnant women, there is a decrease in cholestasis, elimination of itching. In jaundice in pregnant women artichoke extract provides hepatoprotective effect, reduces intrahepatic cholestasis, normalizes bilirubin levels in the blood. Since many diseases in pregnancy are accompanied by activation of lipid peroxidation, changes in the structural properties of cell membranes, metabolic disorders, the use of artichoke extracts is completely justified. Detoxication, antioxidant, lipidormalizing and hepatoprotective properties of preparations based on artichoke extracts indicate the high feasibility of their use in obstetric practice.

Many of the beneficial effects on productive performance observed when vegetable extracts are incorporated as feed additives in intensive farming can be explained by an increase in bile production. An experiment was conducted to study choleretic and cholagogue effect of a Cynara scolymus extract formulation and of silymarin in pigs. Pigs were cannulated with a T-tube catheter in the bile duct. Bile production was continuously measured and re-infused to the duodenum through Oddi’s sphincter at the same production rate. Treatments: Group A (n = 6), commercial feed; Group B (n = 6), C. scolymus extract (300 g/tonne) and Group C (n = 6), silymarin (300 g/tonne). Bile production was recorded hourly for each animal during 24 h. Total bile acids’ concentrations in bile, just before and one hour after meals were evaluated. Average daily bile production for pigs in group B was 66% higher than for pigs in groups A or C (P

An annual herb, native to India, that grows at high altitudes in the subtemperate regions of the Himalayas. The plant has been in use by Hindu physicians for centuries due to its tonic, anthelmintic and febrifuge properties. It is prescribed in masked forms of malarial fever in which the chief symptoms are dyspepsia, and is usually combined with aromatics, such as ginger and lemon-grass; it is also considered laxative and alterative. Muslim physicians of India mentioned it as a remedy for cold and bilious affections, burning of the body and the fever, called sannipat (fever with delirium), arising from derangement of the three humours. Galen described it as diuretic and emmenagogue. It is a bitter tonic, stomachic, laxative, anthelmintic and febrifuge; stimulates appetite, digestion, diminishes flatulence, hyperacidity, and biliousness, and used in the treatment of atonic dyspepsia, liver affections, and intermittent fevers. In Nepal it is considered an important medicinal plant and is used for various diseases including type-2 diabetes. European practitioners in India used it as a substitute for official gentiana preparations. Its usefulness in Unani medicine as a bitter tonic, febrifuge, stomachic, laxative and blood purifier, used for leprosy, gonorrhea, and skin diseases, and also as a beneficial remedy for lung, liver, stomach and kidney ailments is well recognized. It is one of the most frequently used species in traditional Tibetan medicine for the treatment of liver diseases. In China, Swertia pseudochinensis is known as Dangyao, whose properties are described similar to S. chirata, such as it tastes bitter, has a cold property, clears up “damp-heat” and is reputed as stomachic, chloretic and cholagogue; used in infectious hepatitis, acute and chronic bacillary dysentery, and anorexia. Phytoconstituents isolated from the plant include a large number of xanthones, glycosides, alkaloids and other compounds, like chiratin, ophelic acid, palmitic acid, oleic acid, and stearic acid. Ethanol extract of whole plant produced significant blood glucose-lowering effect in fed, fasted and glucose-loaded rats, and enhanced hypoglycemic effect of tolbutamide in rats. Various extracts of the plant and their fractions demonstrated protective activity against CCl4-, galactosamine-, and APAP-induced hepatotoxicity in rats and mice.

The Ebers papyrus mentions external application of garlic for indurations. Hippocrates prescribed eating garlic as treatment for uterine tumors, and Dioscorides as official physician of the Roman army specified garlic for intestinal and lung disorders occurring among Roman troops in Asia. A preparation of garlic and vinegar known as the Four Thieves was credited with protecting citizens of Marseilles when plague struck in 1722. Louis Pasteur reported antibacterial activity of garlic in 1858. The Hindus consider it to be tonic, hot, digestive, aperients, cholagogue, and alterative; useful in cough, and phlegmatic affections, fever, swellings, gonorrhea, piles, leprosy, colic, rheumatism and worms. In the Raja Nirgantha it is described under the name of Rasona, and bears many synonyms indicative of its properties, such as Ugra-gandha (strong smelling), Mahanshadha (panacea), and Bhuta-ghna (destroying demons), and Lasuna. Epidemiological studies indicate that consumption of garlic is inversely associated with cancer risk. In Chinese medicine, garlic, known as Dasuan, is credited as vital-energy-stimulant, spleen- and stomach-warming, digestant, anti-inflammatory, detoxicant, and anthelmintic. Sulfur-containing compounds, the odoriferous substances in garlic are principally made of diallyl disulphide, together with smaller quantities of diallyl trisulphide and diallyl polysulphide. Allin serves as the precursor of alliin, allicin, diallylsulphide and ajoene. When garlic bulb is crushed, alliin present in fresh garlic is converted by the enzyme alliin lyase or alliinase into allicin. Allicin and diallyl disulphide combine to form ajoene, the diallyl disulphide being formed from allicin by heat. Allicin, a water-soluble substance, is responsible for the strong characteristic odor of garlic, is the major potent platelet antiaggregator, and is active against Gram-positive and Gram-negative bacteria, as well as against acid fast organisms. Garlic extracts have shown anticancer, antiatherogenic, antibacterial, blood cholesterol lowering, fibrinolytic, and platelet antiaggregation activities. Garlic oil inhibits human platelet aggregation by interfering with TXB2 synthesis. Meta-analyses of clinical studies agree that garlic supplementation, especially aged garlic, reduces both SBP and DBP in hypertensive patients, reduces TC and LDL-C, decreases platelet aggregation, prevents LPO of oxidized erythrocytes and LDL, increases antioxidant status, stimulates immune system, and exhibits anticancer activity.

A perennial, twining, very small, shrubby and diffuse plant, that is native of eastern Mediterranean basin, Syria, western Asia, and Greek Islands; also grows in India. The gum resin (scammony resin), obtained by incising the fresh root, occurs in flattened cakes or irregular pieces of a brown, dark-grey or nearly black color, and often covered with a greyish-black powder, brittle and glossy. It is a hydrogogue or cholagogue cathartic and anthelmintic; more active than Jalap, acts very promptly, causes severe gripping, colic and watery stool. It is largely used in dropsy, anasarca, cerebral affections, torpid liver and in intestinal catarrh with shiny intestinal mucous. Also used for tapeworms, and due to its insipid taste can be given to children in constipation and as vermifuge for roundworms and tapeworms. In Unani medicine, it is used after a purification process to avoid gastrointestinal adverse effects. The sap contains resin, gum, sugar, and starch. Root contains an active principle jalapin—identical with convolvulin of Jalap. Scammony is inert by itself, until it combines with bile in small intestine and forms a strong purgative complex that stimulates liver and intestinal glands secretion.

EgeUn###, INTRODUCTION: Risk stratification based on biochemical variables is a useful tool for monitoring ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC). Several UDCA response criteria and scoring systems have been proposed for risk prediction in PBC, but these have not been validated in large external cohorts. METHODS: We performed a study on data of 1746 UDCA-treated patients with PBC from 25 centers in Europe, United States, and Canada. The prognostic performance of the risk scoring systems (GLOBE and UK-PBC) and the UDCA response criteria (Barcelona, Paris I, Paris II, Rotterdam, and Toronto) were evaluated. We regarded cirrhosis-related complications (ascites, variceal bleeding, and/or hepatic encephalopathy) as clinical end points. RESULTS: A total of 171 patients reached a clinical end point during a median 7 years (range 1-16 years) of follow-up. The 5-, 10- and 15-year adverse outcome-free survivals were 95%, 85%, and 77%. The GLOBE and UK-PBC scores predicted cirrhosis-related complications better than the UDCA response criteria. The hazard ratio (HR) for a 1 standard deviation increase was HR 5.05 (95% confidence interval (CI): 4.43-5.74, P < 0.001) for the GLOBE score and HR 3.39 (95% CI: 3.10-3.72, P < 0.001) for the UK-PBC score. Overall, the GLOBE and UK-PBC risk scores showed similar and excellent prognostic performance (C-statistic, 0.93; 95% CI: 0.91%-95% vs 0.94; 95% CI: 0.91%-0.96%). DISCUSSION: In our international, multicenter PBC cohort, the GLOBE and UK-PBC risk scoring systems were good predictors of future cirrhosis-related complications.

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.

Curcuma longa from Zingiberaceae belongs to the major spices consumed around the world, known from its cholagogue, anti-inflammatory, and antimicrobial properties. Lack of data on the activity of single components of turmeric extract encouraged the authors to apply TLC (thin-layer chromatography) based bioautography studies to reveal its antimicrobial constituents and construct a universal platform for the bioactivity assessment of crude extracts, with help of a freeware ImageJ software. This optimized chromatographic bioassay performed on diethyl ether and methanol extracts of Curcuma longa was successfully applied on the total extract and revealed the antimicrobial potential of single components against a variety of Gram-positive strains, with no need for their isolation from the mixture. The obtained results were further confronted with a classic microdilution antimicrobial assay on the isolates, purified from the crude extracts by centrifugal partition chromatography in the following solvent system: heptane-chloroform-methanol-water (5:6:3:2) (v/v/v/v).

The seriated extracts of petroleum ether (PE-E), dichloromethane (DCM-E) and methanol extracts (MeOH-E) from the aerial parts of the native South American plant Tetraglochin ameghinoi (Rosaceae), were evaluated regarding their antioxidant and antibacterial activities. The antioxidant properties were evaluated by free radical scavenging methods (DPPH and TEAC), ferric-reducing antioxidant power (FRAP) and lipoperoxidation in erythrocytes (LP), while the antibacterial activity was performed against Gram-positive and Gram-negative bacteria according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. The chemical and biological analyses of this plant are very important since this bush is currently used in traditional medicine as a cholagogue and digestive. The polar MeOH-E showed the highest antioxidant activities (17.70 µg/mL in the DPPH assay, 381.43 ± 22.38 mM TE/g extract in the FRAP assay, 387.76 ± 91.93 mg TE/g extract in the TEAC assay and 93.23 + 6.77% in the LP assay) and it was selected for chromatographic isolation of its components. These components were found to be four acetophenones, including the new phloracetophenone glucoside: 4,6,-dihydroxy-2-O-(6”-acetyl)-β-D-glucopyranosylacetophenone or IUPAC name: (6-(2-acetyl-3,5-dihydroxyphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)methyl acetate, whose structure was elucidated by NMR and MS methods. In addition, twenty-six compounds, including five of these acetophenone derivatives, two sugars, six flavonoids, eleven phenolic acids and two triterpenes, were identified based on UHPLC-OT-MS and PDA analysis on the MeOH-E. The results support the medicinal use of the plant. Fil: Luna, Lorena Celina. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; Argentina Fil: Simirgiotis, Mario J.. Universidad Austral de Chile; Chile Fil: Lima, Beatriz Viviana. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; Argentina Fil: Bórquez, Jorge. Universidad de Antofagasta; Chile Fil: Feresin, Gabriela Egly. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; Argentina Fil: Tapia, Alejandro. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; Argentina

Sandy everlasting [Helichrysum arenarium (L.) Moench] is herbaceous perennial plant belonging to Asteraceae family and it is native to Europe, Central Asia, and China. It belongs to the section HELICHRYSUM (Asteraceae family, genus Helichrysum) along with H. plicatum DC. Prodr., which very similar phenolic profile and H. italicum (Roth), which is widely used for essential oil extraction. Its flowers have a long tradition in European ethnomedicine as a cholagogue, choleretic, hepatoprotective, and detoxifying herbal drug. The flowers are rich in phenolic compounds including flavonoids, chalcones, phenolic acids, coumarins, and pyrones. Apart from polyphenols, other compounds such as sterols, lignans, and glycosides of aromatic compounds have been also isolated from H. arenarium. The majority of authors confirm that the most important group of compounds responsible for biological activities is flavonoids. Moreover, significant activities of naringenin, one of the main flavonoids of H. arenarium, were reported. On the other hand, there are no clinical data about testing the extracts or preparations based on H. arenarium. Although H. arenarium is well known in phytotherapy for its potential in the treatment of gallbladder disease and are classified as endangered species in a number of European countries, very few data about its cultivation are available in the literature.

Introduction . There are over 12 000 medicinal plants encountered nowadays which are a biogenetically formed complex of biologically active compounds (BAC) and are extensively used in scientific as well as folk medicine. The plants which are used as food products and contain a large number of biologically active compounds are of great importance. Artichoke ( Cynara scolymus L.) from Asteraceae family belongs to the group of plants which due to the presence of different groups of BAC is widely used as cholagogue, hepatoprotective, diuretic, antisclerotic, anti-inflammatory, analgesic, hypoglycaemic agent. BAC of artichoke is represented by carbohydrates, hydroxycinnamic acids, flavonoids, essential oil etc. The aim of the study – identification and determination of the quantitative content of inulin in the artichoke inflorescences collected inUkraine andFrance. Methods of the research. The presence of inulin in the studied plant material was confirmed using the Molisch’s test. The quantitative content of inulin in the artichoke inflorescences was determined spectrophotometrically (method 1) and by the means of GC chromato-mass-spectrometric method (method 2). Results and Discussion . The appearance of the dark-violet coloring confirmed the presence of inulin in both samples of the plant material studied. The content of fructosanes’ sum, determined spectrophotometrically, was found to be 2.31 % in the artichoke inflorescences collected inUkraine, and 2.77 % in those collected inFrance. The content of inulin determined by the means of GC chromato-mass-spectrometry comprised 119.30 mg/ml and 147.60 mg/ml respectively. Conclusions . The presence of inulin was confirmed using the Molisch’s test in both samples of artichoke inflorescences. The content of inulin in the artichoke inflorescence collected inUkraineandFrancewas determined by the means of spectrophotometric and GC chromato-mass-spectrometric methods of analysis, and comprised 2.31% and 119.30 mg/ml respectively in the artichoke inflorescences collected inUkraine, and 2.77% and 147.60 mg/ml respectively in the artichoke inflorescences collected inFrance. The results obtained allow considering the plant material of artichoke of Ukrainian and French origin interchangeable for the biologically active substances obtaining.

1. This study is performed to investigate liver microsomal glucuronidation of Armillarisin A (A.A), an effective cholagogue drug, aiming at characterizing the involved UDP-glucuronosyltranferases (UGT) and revealing potential species differences. 2. A.A glucuronidation in human liver microsomes (HLM) generates one metabolite (M2) glucuronidated at the phenol hydroxyl group, obeying Michaelis-Menten kinetic model. Multiple isoforms including UGT1A1, 1A7, 1A9 and 2B15 can catalyze A.A glucuronidation. Kinetic assays and chemical inhibition studies both demonstrate that UGT1A9 is responsible for A.A glucuronidation in HLM. A.A glucuronidation in Cynomolgus monkey microsomes (CyLM) also follows Michaelis-Menten model, but can additionally catalyze the traced glucuronosyl substitution at the alcohol hydroxyl group (M1). The reactions in liver microsomes from Sprague-Dawley rats (RLM), ICR/CD-1 mouse (MLM), Beagle dog (DLM) all display biphasic kinetics and only M2 is detected. HLM, RLM and CyLM exhibit very similar catalytic activities towards A.A glucuronidation, with the intrinsic clearance values of respective 38, 37 and 37 μL/min/mg, which are much higher than MLM and DLM. 3. This in vitro study indicates that UGT1A9 acts as a major contributor to A.A glucuronidation in human liver, and the reaction displays large species differences.

Essential oils and lemon tree oil (Citrus limon (L.) Burm. f./zest) have been known about and used for a very long time, not only in cooking but also in cosmetics and in treatments. Recent studies into d-limonene, present in between 65 and 70% of these products, confirm traditional activity (anti-infective, cholagogue, anti-nausea, tonic, etc.) as well as proposing new properties (anti-cholesterolaemic, lipolytic, hypoglycaemic, ulcer protection, anxiety relief, etc.). The absence of oral toxicity of d-limonene presents a major benefit. Its use in new treatments against metabolic disorders could also be considered.

Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by biliary destruction, progressive cholestasis, and potentially liver cirrhosis. Patients develop a well-orchestrated immune reaction, both innate and adaptive, against mitochondrial antigens that specifically targets intrahepatic biliary cells. A puzzling feature of PBC is that the immune attack is predominantly organ specific, although the mitochondrial autoantigens are found in all nucleated cells. The disease results from a combination of genetic and environmental risk factors; however, the exact pathogenesis remains unclear. Serologically, PBC is characterized by presence of antimitochondrial antibodies, which are present in 90–95 % of patients and are often detectable years before clinical signs appear. Like other complex disorders, PBC is heterogeneous in its presentation, symptomatology, disease progression, and response to therapy. A significant number of patients develop end-stage liver disease and eventually require liver transplantation. Recent studies from large international cohorts have better identified prognostic factors, suggesting a change in patient management based on risk stratification. Therapeutic options are changing. In this review we discuss data on the autoimmune responses and treatment of the disease. © 2017, Asian Pacific Association for the Study of the Liver.

Nutritional support in critically ill patients is a fundamental principle of patient care. Little is known about gallbladder motility during the interdigestive phase and in response to enteral feeding. The objective of this study was to investigate the effect of enteral feeding on gallbladder function in dogs. The cholagogue meal (Lipofundin infusion) was applied in four anatomical positions (jejunum, duodenojejunal junction, descending duodenum, stomach) in five healthy Beagle dogs. Gallbladder volume (GBV) was monitored by ultrasonography. Lipofundin infusion given through the feeding tube caused a maximal gallbladder contraction of 9.2% (range 3.7–13.9%) in the jejunum, 16.5% (9.1–22.1%) at the duodenojejunal junction and 26.3% (22.8–29.5%) in the descending duodenum. When the cholagogue meal was given through the mouth, it caused a mean 33.8% (28.6–46.5%) maximum gallbladder contraction in the same animals. In conclusion, we can establish that the ultrasound-guided gallbladder emptying method proved to be a useful technique for monitoring the cholagogue effect of Lipofundin meal applied in different anatomical positions of the intestine. The deeper the position of application, the smaller and shorter gallbladder contraction was evoked.

The efficacy of ultrasound-guided cholagogue-induced gallbladder emptying for differentiating obstructive from non-obstructive hepatobiliary diseases was studied in icteric dogs. In 7 healthy Beagle dogs, Lipofundin 20% infusion (2 ml/kg orally) evoked a vigorous gallbladder contraction of 44.2% (range: 35.3–57.6%) and proved to be a useful, well-tolerable meal for routine use. In 24 icteric dogs, gallbladder contraction was evoked by different cholagogues: the maximum reduction in gallbladder volume (%) for the three non-obstructive icteric dogs was 43.9% (range, 39.0–46.5%). The average gallbladder contraction of the 21 dogs with biliary obstruction was less than 5%. In conclusion, the stimulation of gallbladder contraction with orally applied magnesium sulphate (MgSO4) or Lipofundin can be well demonstrated by ultrasound in dogs. The examination of cholagogue-induced gallbladder emptying is a valuable technique in icteric patients to indicate surgical intervention.

Rosmarinus officinalis L. (Family Lamiaceae), popularly named rosemary, is a common household plant grown in many parts of the world, including Brazil. Rosemary leaves are used for food flavoring and have been used in folk medicine for many conditions; they have antispasmodic, analgesic, antirheumatic, carminative, cholagogue, diuretic, expectorant, and antiepileptic effects. The objective of this study was to evaluate the effects of rosemary essential oil (REO) on experimental models of nociception and inflammation in animals. The anti-inflammatory effect of REO was evaluated by inflammatory exudate volume and leukocyte migration in carrageenan-induced pleurisy and carrageenan-induced paw edema tests in rats. Antinociception was evaluated using the acetic acid-induced writhing and hot plate tests in mice. REO (500 mg/kg) significantly reduced the volume of pleural exudate and slightly decreased the number of cells that had migrated compared with the control animals. At doses of 250, 500, and 750 mg/kg, REO significantly inhibited carrageenan-induced edema 1-4 hours after injection of the phlogistic agent. In the hot plate test, REO administration (125, 250, and 500 mg/kg) showed unremarkable effects on response latency, whereas control injection of meperidine induced significant antinociceptive effects. REO at doses of 70, 125, and 250 mg/kg had a significant antinociceptive effect in the acetic acid-induced abdominal writhing test compared with control animals. These data suggest that REO possesses anti-inflammatory and peripheral antinociceptive activity.

The use of mint species in traditional and conventional medicine is mostly due to the presence of two classes of secondary bimolecules: monoterpenoids in essential oils and different structural types of phenolic compounds. Essential oils are known to act as antimicrobial, antispasmodic, carminative, and antiviral agents. In addition, essential oils of several mint species have been recently qualified as natural antioxidants. However, since oil composition is highly variable, the pharmacological activity strongly depends on certain chemorace. On the contrary, composition of phenolic constituents is relatively stable within species. The most important phenolic compounds in Mentha species are flavonoids. Mints are characterized by the presence of specific lipophilic flavonoids. Phenolic compounds of mints are found to poses a wide range of pharmacological activity: antioxidant, antiulcer, cytoprotective, heptoprotective, cholagogue, chemopreventive, anti-inflammatory, antidiabetogenic etc. However, besides healing properties some mint species can exhibit an adverse effect on human health. Here we report on botany, chemistry and activity of Mentha species with special respect to their significance for the modern phytotherapy.

In 3 patients with hypothyroidism we tried to quantify the kinetics of the gallbladder using a simple sonographic method. The width of the gallbladder was found to be a good parameter for this purpose after we had found a good correlation between the relative decrease of the width with the relative decrease of the plane and the volume in a control group of 7 persons (R = 0.80, p less than 0.05, R = 0.85, p less than 0.05 respectively). After therapy, the speed of decrease of the width was 8-fold after cholagogue (p less than 0.05) and the increase of the shortening fraction was 13-fold (p less than 0.05). It was concluded that the width of the gallbladder in the examined group of patients reflects thyroid hormone application very sensitively. In view of the small number of patients this finding must be confirmed in a study involving a larger group of patients.

Chelidonii herba has long been known in herbal medicine for its choleretic, cholagogue, spasmolytic and antiviral activities. It is important to monitor the amount of mineral elements in Chelidonii herba preparations consumed mainly for their phytotherapeutical effects. In addition to organic compounds, dissoluble mineral elements in the teas and tinctures of herbs may also have a role in therapy. The concentration of 24 elements (Al, As, B, Ba, Ca, Cd, Co, Cr, Cu, Fe, Hg, K, Li, Mg, Mn, Mo, Na, Ni, P, Pb, S, Ti, V, Zn) in crude drugs (herb and root), in their aqueous solutions (infusion, decoction) and alcoholic extracts were studied by ICP-OES. The difference between the concentration of elements in extracts - except for copper, manganese and sodium - was highly significant. It has been found that the root contains higher concentrations of mineral elements except for boron, copper, phosphorus and sulphur. The infusion contained most elements in the highest concentration and proved to be the best source for obtaining minerals. The same tendency was observed in the case of dissolutions. In aqueous extracts, the dissolution of mineral elements was between 10% and 65% for most elements, especially for potassium (65%) and phosphorus (54%). The dissolution of mineral elements in the case of tinctures decreased with increasing alcohol concentration. It may be stated that the presence of macro- and microelements in extracts greatly contribute to their therapeutical value.

The radish (Raphanus raphanistrum subsp. sativus) is an edible root vegetable of the Brassicaceae family that was domesticated in Europe in pre-Roman times. The root is best harvested before the plant flowers. Its use is not recommended if the stomach or intestines are inflamed. The leaves, seeds and old roots are used in the treatment of asthma and other chest complaints. The juice of the fresh leaves is diuretic and laxative. The seed is carminative, diuretic, expectorant, laxative and stomachic. It is taken internally in the treatment of, abdominal bloating, wind, acid regurgitation, diarrhea and bronchitis. The root is antiscorbutic, antispasmodic, astringent, cholagogue, and diuretic. Antimicrobial proteins and peptides in plants have most commonly been discovered in seeds where they accumulate to high level and may also function as storage proteins. The crude water extract of seed inhibited moderate antifungal activity while showed highest antibacterial activity against Hafnia alvei and Enterobacter agglomerans exhibited. It has been observed that rude water extract posses highest antibacterial activity. Crude water extract showed significant inhibition against some fungal strain like Spadicoides stoveri and Paecilomyces variotii while some fungal strain having insignificant inhibition.

Sonography of gallbladder kinetics shows that a cholagogue exercising a spasmolytic action counteracts the periodic voiding of the gallbladder or even induces an increase in volume of the gallbladder in healthy persons and in patients with cholecystolithiasis. This effect cannot be seen in chronic cholecystitis.

In five female patients with hyperthyroidism the motor function of the gallbladder was examined using sonography. After therapy, the fasting volume and the volume resulting 30 minutes after cholagogue showed a tendency to increase (p approximately 0.15, p approximately 0.25, respectively). The emptied volume and the rate of emptying showed no changes. Although our findings failed to attain statistical significance they suggest an influence on the motor function of the gallbladder resembling a "hypertonic gallbladder". It will be necessary to study a significantly greater number of patients to confirm this thesis.

Background: The extract of medicinal plants containing curcumin is traditionally believed to have a positive contraction effect on the human gall-bladder. Aims: To compare the effect of 20 mg curcumin or placebo on the gall-bladder volume of healthy volunteers. Methods: A randomized, double blind and crossover design study was carried out in 12 healthy volunteers (seven males and five females). Ultrasonography examination was carried out serially to measure the gall-bladder volume. The data obtained was analysed by paired Student’s t-test. Results The fasting gall-bladder volumes of 15.74 ± 4.29 mL on curcumin and 15.98 ± 4.08 mL on placebo were similar (P > 0.20). The gall-bladder volume was reduced within the period after curcumin administration. The percentage of gall-bladder volume reduction at 0.5, 1.0, 1.5 and 2.0 h after 20 mg curcumin administration were 11.8 ± 6.9, 16.8 ± 7.4, 22.0 ± 8.5 and 29.3 ± 8.3%, respectively, which was statistically significant compared to placebo. Conclusion: On the basis of the present findings, it appears that curcumin induces contraction of the human gall-bladder.

We investigated the effect of sodium tauroursodeoxycholate (UR-906) on cholestasis in common bile duct-ligated rats in comparison with the effect of dehydrocholic acid. UR-906 (30-180 mumol/kg) and dehydrocholic acid (180 mumol/kg) were intravenously given once daily for consecutive 20 days in rats and the common bile duct was ligated for the last 10 days. On the next day after the last test drug administration, serum biochemical and plasma hemostatic variables were determined. UR-906 significantly ameliorated the elevation of serum cholesterol, phospholipid, bilirubin and bile acid concentrations in bile duct-ligated rats. UR-906 significantly suppressed the prolongation of plasma prothrombin time and activated partial thromboplastin time. Furthermore, UR-906 significantly suppressed the decreases in plasma coagulation factor II and X activities. However, dehydrocholic acid did not cause significant changes in any of the variables examined in this model. These results suggest that UR-906 has a beneficial effect against cholestasis induced by bile duct ligation in rats and that this drug may be useful in the treatment of clinical cholestatic disorders.

The effect of cholagogues on the volume of the gallbladder was studied by two-dimensional ultrasonography in six healthy dogs fasted for 24 hours. The volume was measured immediately before the administration of each test substance and at 10-minute intervals for 120 minutes thereafter. Tap water administered orally as a control did not elicit significant contractions; only the normal cyclic contractions of the gallbladder, occurring at intervals of 60 to 90 minutes, were recorded. Magnesium sulphate (500 mg as a 20 per cent aqueous solution given orally) and clanobutin (15 mg kg bodyweight−1 given intravenously) reduced the volume of the gallbladder by 24 per cent, and the volume then gradually increased at a rate which was almost identical for the two drugs. The cholagogic hormone cholecystokinin (administered intravenously at a dose rate of 0·04 μg kg bodyweight−1) reduced the volume of the gallbladder by 40 per cent 10 minutes after its administration, and the volume was still markedly decreased 30 to 50 minutes after dosing. The results indicate that magnesium sulphate and clanobutin exert a direct effect on the motor activity of the gallbladder.

The genusCitrus(Rutaceae) includes several species of plants that produce some of the most cultivated fruits in the world, providing an appreciable content of essential oil. In folk medicine, they are used as a cholagogue, antipyretic, anti-inflammatory, sedative, and antitoxic effects. Lemon essential oil has been used since ancient times for its antiseptic, carminative, diuretic, and eupeptic effects. In this study, we investigated the anti-inflammatory activity ofCitrus latifoliaTanaka essential oil (CLEO) and its main constituent LIM. In the cell viability assay, CLEO and LIM (3, 10, 30, and 90 μg/mL) had low cytotoxicity. In zymosan-induced peritonitis, LIM (500 mg/kg) decreased the infiltration of peritoneal exudate leukocytes and decreased the number of polymorphonuclear leukocytes.In vitrochemotaxis revealed that CLEO and LIM (1, 3, and 10 µg/mL) promoted a significant reduction of neutrophil migration toward fMLP and LTB4. LIM (500 mg/kg) also reduced TNF-αlevels but did not alter IL-10 levels in the peritoneal exudate. In conclusion, this study showed that LIM isolated from CLEO had potential anti-inflammatory effects, likely by inhibiting proinflammatory mediators present in inflammatory exudate and leukocyte chemotaxis.

The purpose of this study was to investigate the physicochemical/biological properties and the effects of acute administration of N-ethyl-tauroursodeoxycholic acid in bile-fistula rats. In vitro determination of high-performance liquid chromatography mobility, octanol/ water partitioning, cholesterol solubilizing capacity, and sensitivity to enzyme deconjugation by bacteria and cholylglycine-hydroxylase were performed. In vivo determination of the following was also performed: (1) maximum secretory rate (SRmax) and choleretic/secretory properties during intravenous (IV) administration; (2) site/ extent of absorption, effects on bile flow, lipid secretion, and biotransformations after intraduodenal infusion. N-ethyl-tauroursodeoxycholate has a lipophilicity slightly higher than tauroursodeoxycholate, close to taurocholate, and similar cholesterol solubilizing capacity. Deconjugation of N-ethyl-tauroursodeoxycholate was 3.4 +/- 2.1% after 72 hours, that of tauroursodeoxycholate was 100% after 24 hours. During IV infusion of 300 nmol/min/ 100g, biliary secretion of N-ethyl-tauroursodeoxycholic and tauroursodeoxycholic acids averaged 185 +/- 76 (standard deviation) nmol/min/100 g and 221 +/- 77 nmol/min/ 100 g (not significant). Increasing infusion rates caused progressive enhancement of bile flow and bile salt secretion until the SRmax was reached (1,305 +/- 240 nmol/min/ 100 g for N-ethyl-tauroursodeoxycholic acid and 3,240 nmol/min/100 g for tauroursodeoxycholate). The two bile salts were similarly choleretic. IV feeding of N-ethyl-tauroursodeoxycholic promoted a greater lipid secretion than tauroursodeoxycholate. After intraduodenal feeding of 800 mumol, 38.8 +/- 14.0% and 43.4 +/- 12.4% of the two bile salts were recovered in bile. No unconjugated bile salts nor unusual metabolites were detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Plant secondary metabolic compounds with the cholagogue mode of action are important therapeutic agents for the treatment of cholestasis and hepatobiliary disorders. Herbal cholagogues target different components of the complex bile production and secretion system, and exert their action via diverse routes, such as cholecystokinin-dependent and independent gallbladder contraction, up-regulation of the bile acid synthesis, stimulation of the bile salt export pump, multidrug resistance protein transporter system, and osmotic bile flow.

To determine the absorption and metabolism of 17β-estradiol (E2) by the rectum of the pig, 10 mg of crystalline E2 was placed in the rectum of prepubertal gilts in Experiment 1. Blood samples were subsequently obtained from hepatic portal and jugular veins and plasma was assayed for E2, estrone (E1), 17β-estradiol-glucuronide (E2G), estrone-glucuronide (E1G) and estrone-sulfate (E1S). Concentration of E2, E1, E2G, E1G, and E1S rose in the hepatic portal vein within 30 min and remained elevated for several hr. Concentrations of E2 in the hepatic portal vein represented 3% of the total estrogen detected in the hepatic portal vein during the 5 hr sampling period, indicating that most of the E2 was metabolized prior to entering the hepatic portal vein after absorption by the rectal mucosa. Concentrations of E2, E1, E2G, E1G, and E1S rose in the jugular vein and remained elevated for several hr. The rise in E2 and E1 in the jugular vein may have come from E2 and E1 in venous circulation from the rectum that entered the inferior vena cava bypassing the hepatic portal vein and liver. The net result of absorption of E2 from the rectum of gilts was a large rise in unconjugated and conjugated E2 and E1 in the peripheral circulation. In Experiment 2 prepubertal gilts fitted with jugular, hepatic portal, duodenal, and gall bladder catheters were infused into the duodenum with bile from pregnant gilts. Concentrations of E2, E1, E2G, and E1G were determined in gallbladder bile of gilts before infusion and at 470 min. Concentrations of E2G and E1G were determined in hepatic portal and jugular plasma before and after infusion of bile. A cholagogue was given at 480 min and E2G and E1G were measured in plasma from 490 min to 960 min. Concentrations of E2 and E1 in gallbladder bile rose at 470 min and fell to basal concentrations at 970 min. In gilts given the cholagogue, E2G and E1G in both the jugular and hepatic portal veins rose significantly over those in gilts not given the cholagogue. Bile estrogens circulate via the enterohepatic route and factors that influence secretion of estrogens in bile can influence concentrations of circulating estrogens.

This paper describes a successful management of an operated infant with congenital biliary atresia by administering prostaglandin El immediately after Kasai's operation. The infant was a 19-day-old male. He had gray-white stool on the 10th day after birth. On the 19th day he was referred to the hospital because of yellow-stained conjunctiva. Based on closed examination biliary atresia was suspected and laparotomy was carried out on 49th day. Intraoperative findings and cholangiogram were compatible to biliary atresia and hepatic portoenteros-tomy was performed. For the purpose of promotion of bile outflow, the patient was applied to continuous administration of prostaglandin El intravenously. Serum total bilirubin levels (5.8mg/dl) decreased to 2.0mg/dl on the 15th postoperative day and no ascending cholangitis appeared. The patient was discharged from the hospital on 70th day and is strictly followed on an ambulant basis. Prostaglandin El, which is clinically used to preserve the liver, would be expected as a cholagogue in patients with biliary atresia after Kasai's operation.

In an open, exploratory study, the safety of ursodeoxycholic acid (UDCA) in the treatment of primary biliary cirrhosis (PBC) was investigated. Seven patients in stages I to III and two patients in stage IV were treated for 1 year with 1 g/day of UDCA. Clinical symptoms, and alkaline phosphatase, gamma-glutamyltransferase, alanine aminotransferase (GOT) and aspartate aminotransferase (GTP) levels improved significantly within three months and remained at the lower levels for the period of observation. Results of the galactose elimination capacity (4.7 +/- S.D. 1.4 mg/min per kg) and the aminopyrine breath test (0.60 +/- 0.33% dose/kg per mmol CO2) remained unchanged for 1 year. In all patients total serum bile acids increased and quantitatively UDCA became the most important bile acid. In patients in stages I to III this increase, however, was modest, whereas in patients in stage IV, total serum bile acids reached levels of 140 and 157 mumol/l and UDCA, levels of 90 and 103 mumol/l, respectively. It is concluded that UDCA appears to be safe only in stages I to III and that prognostic stratification based on bile acid levels or on the histological stage of the disease should be an important aspect of controlled clinical trials.

d-Limonene shows carminative and cholagogue effects and is used in treatment of gallstone, cholecystitis and angiocholitis. A simple method was developed to determine the concentration of d-limonene in human plasma. d-Limonene and internal standard (naphthalane, C(10)H(18)) were extracted with n-hexane and then injected to GC-MS. Calibration curves were linear (r=0.9990, n=6) in the range of 2-500 ng/ml for d-limonene in human plasma. Limit of detection and quantification were 0.5 and 2 ng/ml, respectively. This rapid and specific method was applied to the clinical pharmacokinetic investigation of d-limonene.

ObjectiveTo establish a rapid and precise detectiv e method of 33.5 kd vesicular protein and to screen an effective treatment of chol elithiasis. MethodsSpecific antibody of the biliary vesicular prot ein was obtained by immunizing rabbits and enzyme-linked immunosorbent assay (E LISA) kit was developed. The concentrations of 33.5 kd vesicular protein in seru m and bile of gallstone patients and control were examined respectively. The eff ects of Cholagogue Dry Syrup and Eulektrol Capsule on decreasing 33.5 kd vesicul ar protein were also studied by ELISA kit. ResultsOne-step ELISA equation was Y= 0.035 X (r=0.99).The vesicular protein concentrations in seru m and bile of cholesterol gallstone group (179.8±97.9 ) mg/L and (213.4±70. 1)mg/L respectively were significantly (P 0.05) higher than in the pigme nt stone group and control. Data showed that, with 2-week administration, Chola gogue Dry Syrup significantly decreased both biliary and serum 33.5 kd vesicular protein of cholesterol gallstone patients, while Eulekrol Capsule and control g roups didn’t have the same results. Conclusion The concentrations o f 33.5 kd protein are different in cholesterol gallstone patients and healthy gr oups which might be related to cholesterol nucleation process. Cholagogue Dry Sy rup is of cholagogic and litholytic effect by decreasing biliary lithogenesis.

A naturally occurring crosslinking agent, genipin, extracted from the fruits of Gardenia jasminoides ELLIS was used by our group to chemically modified biomolecules. Genipin and its related iridoid glucosides have been widely used as an antiphlogistic and cholagogue in herbal medicine. Our previous study showed that the cytotoxicity of genipin is significantly lower than glutaraldehyde. The study was to investigate the feasibility of using genipin to polymerize hemoglobin as a blood substitute. The results indicated that the rate of hemoglobin polymerization by glutaraldehyde was significantly faster than that by genipin and it readily produced polymers with molecular masses greater than 500,000 Da. It was found that the maximum degree of hemoglobin polymerization by genipin was approximately 40% if over-polymerization is to be prevented. With increasing the reaction temperature, hemoglobin concentration, and genipin-to-hemoglobin molar ratio, the duration taken to achieve the maximum degree of hemoglobin polymerization by genipin became significantly shorter. The P50 value of the unmodified hemoglobin was 9 mmHg, while that of the genipin-polymerized PLP-hemoglobin increased to 21 mmHg. It was found in a rat model that the genipin-polymerized PLP-hemoglobin resulted in a longer circulation time than the unmodified hemoglobin. In conclusion, the results of the study indicated that the genipin-polymerized hemoglobin solution has a lower oxygen affinity and a longer vascular retention time than the unmodified hemoglobin solution.

Helichrysum arenarium is a medicinal plant which has been long known in European traditional medicine as a cholagogue, choleretic and hepatoprotective agent. High-performance liquid chromatography coupled to a UV photodiode-array detector (DAD) and an electrospray ionization mass spectrometer (ESI-MS) was used to analyze the phytochemical constituents of its inflorescence extracts (crude methanolic extract and ethyl acetate fraction of hydrolyzed methanolic extract). Eight flavonoids, namely kaempferol, kaempferol-3-O-glucoside, apigenin, apigenin-7-O-glucoside, naringenin, naringenin-5-O-glucoside, naringenin-4’-O-glucoside, quercetin-3-O-glucoside (isoquercitrin), the chalcone derivative isosalipurposide (2’,4,4’,6’-tetrahydroxychalcone-6’-O-glucoside) and chlorogenic acid were identified in H. flos extracts. The characterization of the above constituents was based on the comparison of their retention times, UV and ESI-MS data recorded on-line with those of reference compounds and literature data.

Saliva protects the oral mucosa, inhibiting microbial overgrowth. Hyposalivation, therefore, induces multiple oral disorders, although treatment of hyposalivation is very difficult.A cholagogue, anethole trithione (AT) was administered to patients with symptomatic hyposalivation (xerostomia) caused by senile hypofunction (4 men and 17 women; senile group), medications (6 men and 17 women; drug group), and oral cancer therapy (two men and three women; cancer group). For control groups, an artificial saliva was administered to 45 patients consisting of senile hypofunction (10 men and 16 women), drug-induced xerostomia (3 men and 10 women) and oral cancer therapy-induced xerostomia (four men and two women).Two weeks after administration of AT (6 tablets per day), both nonstimulated salivary flow rate (SFR) and stimulated SFR increased in a statistically significantly manner from 0.76 +/- 0.41 and 5.18 +/- 3.02 to 1.54 +/- 1.33 (P0.05) and 9.07 +/- 4.10 mL/10 min (P0.05), respectively. Of the three groups, the drug group showed the largest increases in both SFRs, from 0.90 +/- 0.54 and 6.29 +/- 4.12 to 1.69 +/- 1.65 and 12.09 +/- 5.10 mL/10 min (P0.05 and P0.02, respectively). Patients in the control group had almost constant SFRs. After AT administration, the salivary viscosity was, however, mildly decreased and concentrations of secretory-immunoglobulin A, lactoferrin, potassium, and chloride in nonstimulated saliva were almost constant. Corresponding with the increase of salivation, oral discomfort and inflammation were improved or resolved in 41 patients of the AT group within about 4 weeks, whereas improvement was observed in only nine patients of the control group.These results indicate that AT sufficiently stimulates salivation and improves xerostomia.

The genus Globularia (Globulariaceae) includes two species in Algeria. One of them is endemic, Globularia eriocephala (Pomel); the other Globularia alypum L., widespread in the Mediterranean region [1], is used in folk medicine. Its leaves are traditionally used as a hypoglycemic agent, laxative [2], cholagogue, stomachic, purgative, and sudorific [3]. In the present paper we report on the qualitative and quantitative analysis of secondary metabolites extracted from the medicinal plant G. alypum, which has been the subject of several chemical and pharmacological investigations [4–10]. Aerial parts of Globularia alypum L. were collected during the flowering season in eastern Algeria (April 2004). A voucher specimen for this material (VAREN/ SB BF Rv /04/04) was deposited at the Herbarium of the Faculty of Sciences, University MentouriConstantine. Air-dried and powdered aerial parts (1280 g) of G. alypum were macerated in an ethanolic solution (70%); the residue was filtered, concentrated, then successively extracted with petroleum ether, trichloromethane, ethyl acetate, and n-butanol. The AcOEt extract (10 g) was applied to a column of silica gel 60 and eluted with a gradient of CHCl3–CH3COCH3 with increasing polarity. Preparative TLC on silica gel 60 F254 using CHCl3–acetone–acetic acid (4:0.25:0.25) led to luteolin, para-coumaric acid, and cinnamic acid, while using CHCl3–acetic acid (4:0.25) led to apigenin. The para-coumaric acid and cinnamic acid have already been isolated from this plant [4, 5]. Flavonic compounds were identified using UV and 1H NMR spectra, chemical transformations, and comparison with authentic samples [11, 12]. Flavonoids 1, 2 have been isolated previously from another species of Globularia [13], but from G. alypum L. this was the first time. Apigenin, C15H10O5, mp 348–350°C, UV (λmax, MeOH, nm): 268, 335; +NaOH: 274, 324, 392; +AlCl3: 274, 300, 348, 382; AlCl3/HCl: 274, 300, 334, 380; NaOAc: 276, 306, 380. 1H NMR (250 MHz, CD3COCD3, δ, ppm, J/Hz ): 7.90 (2H, d, J = 8.7, H-2′, H-6′); 7.02 (2H, d, J = 8.7, H-3′, H-5′); 6.65 (1H, s, H-3); 6.55 (1H, d, J = 2.2, H-8); 6.26 (1H, d, J = 2.2, H-6). Luteolin, C15H10O6, mp 329–331°C, UV (λmax, MeOH, nm): 264, 350; +NaOH: 267, 329, 402; +AlCl3: 273, 303, 422; AlCl3/HCl: 274, 297, 358, 385; NaOAc: 254, 269, 352. 1H NMR (250 MHz, CD3COCD3, δ, ppm, J/Hz): 7.52 (1H, d, J = 2, H-2′); 7.49 (1H, dd, J = 8.4; 2, H-6′); 7.02 (1H, d, J = 8.4, H-5′); 6.62 (1H, s, H-3); 6.55 (1H, d, J = 2, H-8); 6.26 (1H, d, J = 2, H-8).

We conducted in vivo and in vitro studies of the reductive metabolism of the cholagogue, dehydrocholic acid (DHCA). Immediately after the intravenous administration of 1 g of DHCA in normal subjects (n=6), the concentration of the reductive metabolite, 3α-hydroxy-7,12-dioxo-cholanoic acid (unconjugated form), increased sharply in the systemic conjugated form), increased sharply in the systemic circulation, rising to 95.8 μM 10 min after administration. The results of in vitro experiments with DHCA and whole blood showed that 3α-hydroxy-7,12-dioxo-cholanoic acid and 3β-hydroxy-7,12-dioxo-cholanoic acid were produced from DHCA. In vitro experiments using DHCA and the red blood cell fraction, and DHCA and the red blood cell cytoplasmic fraction gave similar results to those described above with whole blood. However, a reductive metabolite was not formed by the incubation of DHCA and the red blood cell membrane fraction. These findings indicated that, contrary to the conventional theory that intravenously administered DHCA is subjected to reductive metabolism only in the liver, reduction also occurs in the systemic circulation, and the mechanism for this reductive metabolism is present in the cytoplasmic fraction of red blood cells. Further investigation to characterize this reductive metabolic system revealed an optimum temperature of 37°C, an optimum pH of 7.4, a Km value of 2.0×10−3M, and inactivation by heart treatment (70°C for 2 min).

The diagnosis of some cases of neonatal jaundice is complicated because of inability to identify the gallbladder, which makes it very difficult to differentiate biliary atresia from neonatal hepatitis even by serial ultrasonic (US) examination. Serial (US) examination after the administration of phenobarbital as a cholagogue at a dosage of 5 mg/kg/day for 5 days was performed to evaluate nine patients with neonatal jaundice. In five of the nine patients, the gallbladder was identified by a change in size following oral feeding. These patients were diagnosed as having neonatal hepatitis. The gallbladders of the other four patients were not identified before, during, or after feeding. They were diagnosed as having biliary atresia and the diagnoses were confirmed by surgery. Administration of phenobarbital for 5 days before serial US examination is very useful in the diagnosis of neonatal hepatitis when differentiation between neonatal hepatitis and biliary atresia is impossible because of inability to identify the gallbladder by US alone.

Hepatic elimination of 4-methylumbelliferone (4MU), which has been used as a model compound for conjugative metabolism, was studied by means of a multiple indicator dilution (MID) method in the isolated perfused rat liver. Using this method, three intrinsic hepatic clearances, CL int,inf , CL int,eff, and CL int,seq, which represent the influx, efflux, and sequestration processes, respectively, were obtained. When the dose was increased from a low dose (50 μg/rat liver) to a high dose (3000 μg/rat liver), the hepatic availability of 4MU increased from 0.11 to 0.73. With increasing dose, the CL int,eff value increased approximately two times, while the CL int,seq value decreased to approximately one-third. The remarkable dose dependence of hepatic availability was due to nonlinearity in both CL int,eff and CL int,seq values. However, the CLint,inf value was almost independent of dose. The dose-dependent change in CLint,seq might be explained by the saturation of conjugative metabolism of 4-MU, while the increase in the CL int,eff value with increasing dose might be partly explained by the nonlinear tissue binding of 4-MU, since the tissue unbound fraction determined by an ultrafiltration method using liver homogenate increased approximately 1.5 times at higher concentration of 4-MU compared to that at lower concentrations. In addition, based on a comparison of the individual intrinsic clearances, i.e., CL int,inf , CL int,eff, and CL int,seq, the major determining process of the apparent hepatic intrinsic clearance of 4MU is thought to be the sequestration process at the high dose. However, at the low dose, the membrane transport process (influx and efflux processes) as well as the sequestration process also determine the apparent hepatic intrinsic clearance.