Characteristics of serum bile acids among healthy children in Zhejiang province / 中华儿科杂志

Objective: To characterize the serum bile acid profiles of healthy children in Zhejiang Province. Methods: A cross-sectional study was conducted on 245 healthy children who underwent imaging and laboratory biochemical tests during routine physical examinations at the Children's Hospital of Zhejiang University School of Medicine from January 2020 to July 2022. Overnight fasting venous blood samples were collected, and the concentrations of 18 individual bile acids in the serum were accurately quantitated using tandem mass spectrometry. The concentration difference of bile acid were compared between different genders and to explore the correlation between age and bile acid levels. Used the Mann-Whitney U test for intergroup comparison and Spearman test to correlation analysis. Results: A total of 245 health children with a age of 10 (8, 12) years including 125 boys and 120 girls. There were no significant differences in levels of total bile acids, primary and secondary bile acids, free and conjugated bile acids between the two gender groups (all P>0.05). The serum concentrations of ursodeoxycholic acid and glycoursodeoxycholic acid in girls were significantly higher than those in boys (199.0 (66.9, 276.5) vs. 154.7 (49.3, 205.0) nmol/L, 274.0 (64.8, 308.0) vs. 181.0 (43.8, 209.3) nmol/L, Z=2.06, 2.71, both P<0.05). The serum taurolithocholic acid in both boys and girls were positively correlated with age (r=0.31, 0.32, both P<0.05). The serum chenodeoxycholic acid and glycochenodeoxycholic acid in the boys group were positively correlated with age (r=0.20, 0.23, both P<0.05), whereas the serum tauroursodeoxycholic acid in the girls group was negatively correlated with age (r=-0.27, P<0.05), and the serum cholic acid was positively correlated with age (r=0.34, P<0.05). Conclusions: The total bile acid levels are relatively stable in healthy children in Zhejiang province. However, individual bile acids showed gender differences and were correlated with age.

Value of the combined use of aminotransferase-to-platelet ratio index and total bile acid for predicting parenteral nutrition-associated cholestasis in preterm infants with gestational age <34 weeks / 中国当代儿科杂志

OBJECTIVES@#To explore the value of the combined use of aspartate aminotransferase-to-platelet ratio index (APRI) and total bile acid (TBA) for predicting parenteral nutrition-associated cholestasis (PNAC) in preterm infants with gestational age <34 weeks.@*METHODS@#A retrospective analysis was performed on medical data of 270 preterm infants born at <34 weeks of gestation who received parenteral nutrition (PN) during hospitalization in the First Affiliated Hospital of Wannan Medical College from January 2019 to September 2022, including 128 infants with PNAC and 142 infants without PNAC. The medical data between the two groups were compared, and predictive factors for the development of PNAC were explored through multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was used to evaluate the value of APRI alone, TBA alone, and the combination of both for predicting PNAC.@*RESULTS@#TBA levels in the PNAC group after 1, 2, and 3 weeks of PN were higher than those in the non-PNAC group (P<0.05). APRI in the PNAC group after 2 and 3 weeks of PN was higher than that in the non-PNAC group (P<0.05). Multivariate logistic regression analysis showed that elevated APRI and TBA after 2 weeks of PN were predictive factors for PNAC in preterm infants (P<0.05). ROC curve analysis showed that the sensitivity, specificity, and area under the curve (AUC) for predicting PNAC by combining APRI and TBA after 2 weeks of PN were 0.703, 0.803, and 0.806, respectively. The AUC for predicting PNAC by combining APRI and TBA was higher than that of APRI or TBA alone (P<0.05).@*CONCLUSIONS@#After 2 weeks of PN, the value of combining APRI and TBA for predicting PNAC is high in preterm infants with gestational age <34 weeks.

Papel del ácido ursodesoxicólico en 40 años de tratamiento para la colangitis biliar primaria / Role of ursodeoxycholic acid in 40 years of treatment for primary biliary cholangitis

La colangitis biliar primaria es una enfermedad hepática autoinmune que conduce a la destrucción progresiva de los conductos biliares intrahepáticos, lo que aumenta el riesgo de desarrollar cirrosis e hipertensión portal. Actualmente, el ácido ursodesoxicólico es el medicamento de primera línea para el tratamiento de esta entidad. Este medicamento desplaza los ácidos biliares hidrofóbicos y aumenta las concentraciones de ácidos biliares hidrofílicos en la bilis, lo cual favorece la integridad de los conductos biliares, adicionalmente, tiene efectos antiinflamatorios y propiedades inmunomo-duladoras y antiapoptóticas. En los últimos 40 años, numerosos ensayos clínicos han respaldado la eficacia clínica del ácido ursodesoxicólico y su seguridad cuando se utiliza en pacientes con colan-gitis biliar primaria. Se realiza una revisión del ácido ursodesoxicólico en el contexto de colangitis biliar primaria, se describe su historia, mecanismos de acción, efectos secundarios y dosificación. Finalmente, se menciona su uso en situaciones especiales como son el embarazo y la lactancia

Primary biliary cholangitis is an autoimmune liver disease that leads to progressive destruction of intrahepatic bile ducts, increasing the risk of developing cirrhosis and portal hypertension. Currently, ursodeoxycholic acid is the first-line drug for the treatment of this condition. This drug displaces hy-drophobic bile acids and increases concentrations of hydrophilic bile acids in the bile, which favors the integrity of the bile ducts, additionally, it has anti-inflammatory effects and immunoprotective and antiapoptotic properties. Over the past 40 years numerous clinical trials have supported the clinical efficacy of ursodeoxycholic acid and its safety when used in patients with primary biliary cholangitis. A review of ursodeoxycholic acid in the context of primary biliary cholangitis is carried out, and its history, mechanisms of action, side effects and dosage are described. Finally, its use in special situations such as pregnancy and lactation are discussed.

Efecto del ácido deoxicólico sobre la regulación del transporte iónico intestinal en la rata / Deoxycholic acid efect on intestinal ionic transport regulation in the rat

The intestine has a very important role in the homeostasis of the internal medium. Bile acids play a regulatory role in the digestion and absorption of nutrients. Among them, deoxycholic acid, when its luminal concentration increases due to bacterial overgrowth, modifies hydroelectrolytic transport, producing an increase in the volume of water and electrolytes in stools.

El intestino tiene un papel muy importante en la homeostasis del medio interno. Los ácidos biliares cumplen una función reguladora en la digestión y absorción de nutrientes. Entre ellos el ácido deoxicólico, cuando aumenta su concentración luminal por sobrecrecimiento bacteriano, modifica el transporte hidroelectrolítico produciendo aumento del volumen de agua y electrolitos en las deposiciones.

Comparative effect of ciprofloxacin and moxifloxacin on the modulation of bile acid profiles and gut microbiota in rats

Abstract Fluoroquinolones are an important class of antimicrobial agents to manage infectious diseases. However, knowledge about how host bile acids are modified by fluoroquinolones is limited. We investigated and compared the impact of fluoroquinolones on circulating bile acid profiles and gut microbiota from in vivo studies. We administered ciprofloxacin (100 mg/kg/day) or moxifloxacin (40 mg/kg/day) orally to male Wistar rats for seven days. Fifteen bile acids (BAs) from the serum and large intestine were quantified by HPLC-MS/MS. The diversity of gut microbiota after ciprofloxacin and moxifloxacin treatment was analyzed using high-throughput, next-generation sequencing technology. The two fluoroquinolone-treated groups had different BA profiles. Ciprofloxacin significantly reduced the hydrophobicity index of the BA pool, reduced secondary BAs, and increased taurine-conjugated primary BAs in both the serum and large intestine as compared with moxifloxacin. Besides, ciprofloxacin treatment altered intestinal microbiota with a remarkable increase in Firmicutes to Bacteroidetes ratio, while moxifloxacin exerted no effect. What we found suggests that different fluoroquinolones have a distinct effect on the host BAs metabolism and intestinal bacteria, and therefore provide guidance on the selection of fluoroquinolones to treat infectious diseases.

Expert consensus on the diagnosis and treatment of intrahepatic cholestasis (2021 edition) / 中华肝脏病杂志

Intrahepatic cholestasis is a clinical syndrome due to the defect of bile acid synthesis, abnormal bile excretion, and mechanical or functional disturbance of intrahepatic bile flows caused by hepatic parenchymal cell and/or intrahepatic bile duct diseases. It commonly occurs as cholestatic liver diseases, intrahepatic cholestasis of pregnancy, and genetic/metabolic-related cholestatic diseases. In recent years, new information and progress in diagnosis and treatment of intrahepatic cholestatic diseases have been achieved. In order to provide updated clinical reference and guidance for clinicians, we organized experts to compile the Expert Consensus on the Diagnosis and Treatment of Intrahepatic Cholestasis (2021), on the basis of the 2015 edition.

Serum metabolomics of Tibetan medicine Ershiwuwei Songshi Pills against chronic cholestasis in mice / 中国中药杂志

A chronic cholestasis model was induced in mice by feeding a diet containing 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine(DDC). The effects of Ershiwuwei Songshi Pills(ESP) on endogenous metabolites in mice with chronic cholestasis were investigated by metabolomics analysis based on liquid chromatography-mass spectrometry(LC-MS). The results showed that ESP was effective in improving pathological injury and reducing serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP), and total bile acid in the model mice. Meanwhile, 13 common differential metabolites were revealed in metabolomic screening between the model/control group and the model/ESP group, including uric acid, glycolaldehyde, kynurenine, flavin adenine dinucleotide, L-3-phenyllactic acid, I-urobilin, leukotriene D4(LTD4), taurocholic acid, trioxilin A3, D-inositol-1,4-diphosphate, PC [16:0/20:2(11Z,14Z)], PC[14:0/22:2(13Z,16Z)], and PC[20:4(5Z,8Z,11Z,14Z)/20:4(5Z,8Z,11Z,14Z)]. After ESP intervention, the levels of all 13 differential metabolites were significantly retraced, and pathway analysis showed that ESP achieved its therapeutic effect mainly by affecting arachidonic acid metabolism, glycerophospholipid metabolism, tryptophan metabolism, and primary bile acid biosynthesis. This study elucidated the mechanism of action of ESP against chronic cholestasis based on metabolites.

Effect of Suanzaoren Decoction on molecular levels of bile acids in serum, liver, and ileum of insomnia mice / 中国中药杂志

To explore the mechanism of Suanzaoren Decoction in the treatment of insomnia from endogenous bile acid regulation, the present study investigated the hepatoprotective effect of Suanzaoren Decoction and the molecular changes of bile acids in the serum, liver, and ileum of insomnia model mice and Suanzaoren Decoction treated mice. The insomnia model in mice was established by the sleep deprivation method. After Suanzaoren Decoction(48.96 mg·kg~(-1)·d~(-1)) intervention by gavage for 7 days, the related indicators, such as water consumption, food intake, body weight, aspartate aminotransferase(AST), alanine transaminase(ALT), and total bile acid(TBA) were detected, and the pathological changes of the liver and ileum were observed. The molecular levels and distribution of 23 bile acids in the serum, liver, and ileum were analyzed by UPLC-MS/MS combined with principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA). The results showed that Suanzaoren Decoction could improve the decreased water consumption and food intake, weight loss, and increased AST and ALT in the model group, and effectively reverse the injury and inflammation in the liver and ileum. The bile acids in the liver of the insomnia model mice were in the stage of decompensation, and the bile acids in the serum, liver, and ileum of the mice decreased or increased. Suanzaoren Decoction could regulate the anomaly of some bile acids back to normal. Seven bile acids including glycoursodeoxycholic acid(GUDCA), glycodesoxycholic acid(GDCA), tauro-α-MCA(T-α-MCA), α-MCA, taurodeoxycholate(TDCA), T-β-MCA, and LCA were screened out as the main discriminant components by PLS-DA. It is concluded that Suanzaoren Decoction possesses the hepatoprotective effect and bile acids could serve as the biochemical indicators to evaluate the drug efficacy in the treatment of abnormal liver functions caused by insomnia. The mechanism of Suanzao-ren Decoction in soothing the liver, resolving depression, tranquilizing the mind, and improving sleep may be related to the molecular regulation of bile acid signals.

Bear bile powder attenuates senecionine-induced hepatic sinusoidal obstruction syndrome in mice / 中国天然药物

Hepatic sinusoidal obstruction syndrome (HSOS) via exposure to pyrrolizidine alkaloids (PAs) is with high mortality and there is no effective treatment in clinics. Bear bile powder (BBP) is a famous traditional animal drug for curing a variety of hepatobiliary diseases such as cholestasis, inflammation, and fibrosis. Here, we aim to evaluate the protective effect of BBP against HSOS induced by senecionine, a highly hepatotoxic PA compound. Our results showed that BBP treatment protected mice from senecionine-induced HSOS dose-dependently, which was evident by improved liver histology including reduced infiltration of inflammatory cells and collagen positive cells, alleviated intrahepatic hemorrhage and hepatic sinusoidal endothelial cells, as well as decreased conventional serum liver function indicators. In addition, BBP treatment lowered matrix metalloproteinase 9 and pyrrole-protein adducts, two well-known markers positively associated with the severity of PA-induced HSOS. Further investigation showed that BBP treatment prevents the development of liver fibrosis by decreasing transforming growth factor beta and downstream fibrotic molecules. BBP treatment also alleviated senecionine-induced liver inflammation and lowered the pro-inflammatory cytokines, in which tauroursodeoxycholic acid played an important role. What's more, BBP treatment also decreased the accumulation of hydrophobic bile acids, such as cholic acid, taurocholic acid, glycocholic acid, as well. We concluded that BBP attenuates senecionine-induced HSOS in mice by repairing the bile acids homeostasis, preventing liver fibrosis, and alleviating liver inflammation. Our present study helps to pave the way to therapeutic approaches of the treatment of PA-induced liver injury in clinics.

Rol de la microbiota intestinal en el desarrollo del hígado graso no alcohólico / The role of intestinal microbiota in the development of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of hepatic pathologies ranging from simple steatosis (SS) to hepatocellular carcinoma. Intestinal microbiota (IM) is composed of trillions of microorganisms existing in the gut. It has 150 times more genes than the host. Changes in the composition and function of the IM are associated with different diseases, including NAFLD. In this condition, IM could have a pathogenic role through different mechanisms such as energy salvaging from food, an inflammatory stimulus, a modulation of the innate immune system, regulation of bile acid turnover, alteration of choline metabolism and increasing endogenous ethanol levels. This review is an update on the role of the intestinal microbiota in NAFLD and the possible mechanisms involved.

Asociación entre los niveles elevados de ácidos biliares y cáncer digestivo / Association between high bile acid levels and digestive cancer

Introducción: Los ácidos biliares en condiciones no fisiológicas se consideran agentes inflamatorio-carcinógenos endógenos que originan alteraciones en membranas plasmáticas, mitocondrias, el ADN, los genes y, la apoptosis de las células epiteliales. Objetivo: Describir la asociación entre los niveles elevados de ácidos biliares en la luz intestinal y la secuencia inflamación-cáncer, expresados como lesiones inflamatorias, premalignas y malignas del tracto digestivo. Métodos: Revisión sistemática y crítica de las evidencias sobre los mecanismos biomoleculares asociados a niveles altos de ácidos biliares en la luz intestinal y la secuencia inflamación-carcinogénesis, en bases de datos como PubMed, Medline, SciELO, LILACS y Elsevier, publicados entre 2015-2020, que establecen el fundamento teórico y metabolómico de dicha secuencia. Resultados: Los ácidos biliares tienen una acción tóxica en la secuencia inflamación-cáncer del tracto digestivo, al perderse el control de su homeostasis o la integridad anatomo-funcional del sistema hepato-vesículo-bilio-intestinal. Conclusiones: Los mecanismos celulares y biomoleculares desencadenados por los niveles altos de ácidos biliares contextualizan la génesis del proceso secuencial inflamación-cáncer y su interacción con los factores de riesgo clásicos, genéticos y epigenéticos reconocidos como un nuevo paradigma fisiopatológico del cáncer digestivo(AU)

Introduction: In non-physiological conditions, bile acids (BA) are considered to be endogenous inflammatory-carcinogenic agents causing alterations in plasma membranes, mitochondria, DNA, genes and epithelial cell apoptosis. Objective: Describe the association between high bile acid levels in the intestinal lumen and the inflammation-cancer sequence, expressed as inflammatory premalignant and malignant lesions of the digestive tract. Methods: A systematic critical review was conducted of the evidence about biomolecular mechanisms associated to high bile acid levels in the intestinal lumen and the inflammation-carcinogenesis sequence published in the databases PubMed, Medline, SciELO, LILACS and Elsevier in the period 2015-2020, laying the theoretical and metabolomic foundations of that sequence. Results: Bile acids display toxic activity in the inflammation-cancer sequence of the digestive tract, since control is lost of its homeostasis or the anatomical-functional integrity of the hepato-vesicular-biliary-intestinal system. Conclusions: The cellular and biomolecular mechanisms triggered by high bile acid levels provide a context for the genesis of the inflammation-cancer sequential process and its interaction with the classic, genetic and epigenetic risk factors recognized as a new pathophysiological paradigm of digestive cancer(AU)

Mechanism of gut-microbiota-liver axis in the pathogenesis of intestinal failure-associated liver disease / 中华胃肠外科杂志

Intestinal failure (IF) is defined as the critical reduction of functional intestines below the minimum needed to absorb nutrients and fluids, so that intravenous supplementation with parenteral nutrition (PN) is required to maintain health and/or growth. Although the benefits are evident, patients receiving PN can suffer from serious cholestasis due to lack of enteral feeding and small intestinal bacterial overgrowth (SIBO). One such complication that may arise is intestinal failure-associated liver disease (IFALD). Evidences from recent studies suggest that alterations in the intestinal microbiota, as well as intraluminal bile acid driven signaling, may play a critical role in both hepatic and intestinal injury. Since Marshall first proposed the concept of the gut-liver axis in 1998, the role of gut-liver axis disorders in the development of IFALD has received considerable attention. The conversation between gut and liver is the key to maintain liver metabolism and intestinal homeostasis, which influences each other and is reciprocal causation. However, as a "forgotten organ" , intestinal microbiota on the pathogenesis of IFALD has not been well reflected. As such, we propose, for the first time, the concept of gut-microbiota-liver axis to emphasize the importance of intestinal microbiota in the interaction of gut-liver axis. Analysis and research on gut-microbiota-liver axis will be of great significance for understanding the pathogenesis of IFALD and improving the prevention and treatment measures.

Study on bile acid metabolism of sleep-deprived mice regulated by Jiaotai Pills based on LC-MS / 中国中药杂志

To investigate the changes of bile acid(BA) levels in mice with sleep deprivation and the regulatory effect of Jiaotai Pills(JTP) on bile acid metabolism, this study established an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of 23 BAs in mice. A total of 24 ICR mice were randomized into normal group, model group, and JTP group. Mice in the model group and JTP group were deprived of sleep at 20 h·d~(-1) by sleep deprivation apparatus for 8 consecutive days. Mice in the JTP group were given(ig, qd) JTP 3.3 g·kg~(-1) and those in the normal group and model group received(ig) the same volume of purified water. UPLC conditions are as follows: Waters ACQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm), gradient elution with the mobile phase of 0.1% formic acid in water-methanol. MS conditions are as below: negative-ion electrospray ionization, multiple reaction monitoring(MRM). Thereby, the content of 23 BAs in serum, liver, and ileum was determined and methodological investigation of the method was performed. The results showed that 23 BAs could be accurately determined within 15 min and the correlation coefficients were all higher than 0.99. The precision, accuracy, specificity, reproducibility, matrix effect, and recovery of BAs all met the requirement. The levels of BAs were significantly increased in the serum, liver, and ileum of sleep-deprived mice, but JTP can significantly reduce the levels. The UPLC-MS/MS method is simple, rapid, and accurate, which can be used for the determination of 23 BAs in biological samples, and JTP can adjust the elevated BA levels of sleep-deprived mice.

Chemical constituents and pharmacological action of bile acids from animal:a review / 中国中药杂志

Bile of animal(mainly chicken, pig, snake, cow, and bear) has long been used as medicine. As the major active components of bile, bile acids mainly include cholic acid, deoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid, and taurochenodeoxycholic acid. They interact with intestinal microorganisms in enterohepatic circulation, thereby playing an important part in nutrient absorption and allocation, metabolism regulation, and dynamic balance. Bile acids have pharmacological effects such as protecting liver, kidney, heart, brain, and nerves, promoting bile secretion, dissolving gallstones, anti-cancer, relieving cough and dyspnea, dispelling phlegm, treating eye diseases, and regulating intestinal function and blood glucose, which are widely used in clinical practice. This study summarized and analyzed the research on the chemical constituents and pharmacological effects of bile acids from medicinal animals, in a bid to provide scientific basis and reference for the further development and utilization of bile acids.

2,3,5,4'-Tetrahydroxystibane-2-O-β-D-glucoside induces liver injury by disrupting bile acid homeostasis and phospholipids efflux / 中国中药杂志

Polygonum multiflorum is a traditional Chinese herbal medicine and has many biological activities such as hair-blacking, anti-atherosclerosis, anti-inflammatory and anti-aging. However, the liver injury induced by P. multiflorum has aroused wide attention in recent years. 2,3,5,4'-tetrahydroxystibane-2-O-β-D-glucoside(TSG) is a main component of P. multiflorum, but the role of TSG in inducing liver injury is unclear. The aim of present study was to evaluate TSG's potential liver injury and effects on bile acid homeostasis and phospholipids efflux. C57 BL/6 J mice received intraperitoneal administration of 400 mg·kg~(-1) of TSG daily for 15 days, and then biochemical indexes of liver injury and changes of phospholipid content were detected. The changes of bile acid compositions were detected by LC-MS/MS. The results showed TSG 400 mg·kg~(-1) significantly increased the content of serum total bile acid(TBA) and alkaline phosphatase(ALP). Elevated free bile acid levels were observed in TSG-treated groups, including β-muricholic acid(β-MCA), ursodeoxycholic acid(UDCA), hyodeoxycholic acid(HDCA), chenodeoxycholic acid(CDCA), deoxcholic acid(DCA) in serum and β-MCA, CDCA in liver. TSG inhibited the protein expression of farnesoid X receptor(FXR) and down stream bile salt export pump(BSEP), which may result in the accumulation of bile acid. TSG also inhibited the expression of 25-hydroxycholesterol-7 alpha-hydroxylase(CYP7 B1), which may disturb the alternative pathway for bile acid synthesis. In addition, intraperitoneal injection of TSG 400 mg·kg~(-1) significantly decreased the content of phospholipids in bile. The research showed that TSG significantly inhibited the expression of multidrug resistance protein 2(MDR2) and destroyed the regular distribution of MDR2 on the bile duct membrane of liver. In vitro results showed that the IC_(50) of TSG on HepG2 cells was about 1 500 μmol·L~(-1) and TSG at 500 μmol·L~(-1)(for 24 h) could destroy the distribution of MDR2 on the bile duct membrane of liver. In conclusion, TSG induced liver injury by disrupting bile acid homeostasis and phospholipids efflux.

Bile acid derivatives-focused chemical profiling in snake bile / 中国中药杂志

As a precious traditional Chinese medicine(TCM), snake bile has been widely used in numerous Chinese medicine prescriptions. Bile acid(BA) derivatives have been demonstrated as the primary chemical family in snake bile. In-depth chemical characterization of BAs is of great importance towards the establishment of quality standards and clarification of the effective material basis for snake bile. This study firstly employed ~1H-NMR to preliminarily analyze the chemical profiles of snake bile, an automated fraction collector was subsequently implemented to obtain the fractions-of-interest. The fraction was then concentrated and re-analyzed by LC-MS. Based on ~1H-NMR, BAs were found to be the main components of snake bile, and six BAs including CDCA, CA, TCDCA, TCA, TDCA and GCA were tentatively identified from the representative spectrum with the assistance of literature and reference compounds. Whereas the content of TCA in snake bile was too great, resulting in a great obstacle for the detection of trace components, the automated fraction collector was subsequently implemented to obtain the fractions-of-interest for LC-MS analysis. According to matching MS/MS information and retention time with reference compounds as well as database retrieval, a total of 57 BAs were detected and annotated. Because of the combination of ~1H-NMR and LC-MS platforms, the findings are beneficial for the in-depth characterization of BAs in snake bile, which provides references for the establishment of quality control and evaluation methods of snake bile.

Actividad biológica y toxicológica de los ácidos biliares en la actualidad / Biological and toxicological activity of bile acids today

Introducción: los ácidos biliares no solo tienen como actividad biológica regular la absorción de vitaminas liposolubles, colesterol y lípidos, sino actúan también como moléculas de señalización, moduladores de la proliferación celular intestinal, de la expresión de genes y del metabolismo energético según estudios in vitro e in vivo; en condiciones fisiológicas mantienen su homeostasis, que al ser interrumpida promueve suacción toxicológica. Objetivo: describir la actualidad de los nuevos conocimientos sobre la actividad biológica y toxicológica de los ácidos biliares en el aparato digestivo, dirigido a cirujanos generales, gastroenterólogos, clínicos y fisiólogos que les permitan contextualizar el proceso inflamación-carcinogénesis relacionado con los efectos toxicológicos de los ácidos biliares. Método: se realizó una revisión sistemática de la actividad biológica y toxicológica de los ácidos biliares para los cirujanos generales, gastroenterólogos, clínicos y fisiólogos, como herramienta útil en la compresión fisiopatológico del metabolismo de los ácidos biliares. Conclusión: los ácidos biliares desempeñan una función clave como moléculas de señalización en la modulación de la proliferación de células epiteliales, la expresión de genes y el metabolismo energético, que cuando se interrumpe su homeostasis se promueve la acción tóxica de estos, lo que se traduce en el proceso inflamación-carcinogénesis digestiva(AU)

Introduction: bile acids not only have as a regular biological activity the absorption of fat-soluble vitamins, cholesterol and lipids, but also act as signaling molecules, modulators of intestinal cell proliferation, gene expression and energy metabolism according to in vitro studies and in vivo; under physiological conditions they maintain their homeostasis, which when interrupted promotes their toxicological action. Objective: to describe the news of the new knowledge about the biological and toxicological activity of bile acids in the digestive system, aimed at general surgeons, gastroenterologists, clinicians and physiologists that allow them to contextualize the inflammation-carcinogenesis process related to the toxicological effects of bile acids. Method: A systematic review of the biological and toxicological activity of bile acids was performed for general surgeons, gastroenterologists, clinicians and physiologists, as a useful tool in the pathophysiological compression of bile acid metabolism. Conclusion: bile acids play a key role as signaling molecules in the modulation of epithelial cell proliferation, gene expression and energy metabolism, which when their homeostasis is interrupted, their toxic action is promoted, which translates in the inflammation-digestive carcinogenesis process(AU)

The diversity of ursodeoxycholic acid precursors from bile waste of commercially available fishes, poultry and livestock in Indonesia

Ursodeoxycholic acid (UDCA), a secondary bile acid (BA), has been used as a drug to treat various liver diseases. UDCA is synthesised from cholic or chenodeoxycholic acid (CA/CDCA), two primary BAs frequently used as the starting materials. Nowadays, swine, cattle, and poultry bile are the main sources of those BAs. However, other commercial animals could be promising sources as well. We identified two livestock, two poultries, and eight fishes that are commercially cultivated in Indonesia. Four free BAs including CA, CDCA, deoxycholic acid (DCA), and lithocholic acid (LA) were identified for their occurrences using thin-layer chromatography and high-performance liquid chromatography. CA was detected in cow, duck, red tilapia, gourami, the common carp, and grouper, whereas CDCA was only detected in two poultries and the common carp. The occurrence of DCA was common and abundant in most tested animals. In contrast, the presence of LA was found to be very low in all samples. The biliary bile of tilapia has been found to contain a high abundance of free CA (43% of the total bile). A simple extraction was able to purify CA from biliary bile of tilapia. This is a new promising and competitive source of CA.

Bile acids regulate anorexigenic neuropeptide through p-STAT3-SOCS3 signaling in mouse hypothalamic cells / 南方医科大学学报

OBJECTIVE@#To explore the effects of taurolithocholic acid (tLCA) and chenodeoxycholic acid (CDCA) on the expression of aorexigenic neuropeptide in mouse hypothalamus GT1-7 cells.@*METHODS@#Mouse hypothalamic GT1-7 cells were treated with culture medium containing 10% FBS (control group, =3) or with 10 nmol/L, 100 nmol/L, 1 μmol/L and 10 μmol/L tLCA (tLCA group, =3) or CDCA (CDCA group, =3) for 12, 24 or 48 h. Real-time PCR was performed to determine the expression levels of proopiomelanocortin (POMC) mRNA in the cells, and the production levels of α-melanocyte-stimulating hormone (α-MSH) were assessed using an ELISA kit. Signal transduction and activator of transcription 3 phosphorylation (p-STAT3), threonine kinase phosphorylation (p-AKT), suppressor of cytokine signaling 3 (SOCS3), G protein-coupled bile acid receptor-1 (TGR5) and farnesoid X receptor (FXR) protein were detected by Western blotting.@*RESULTS@#Western blotting results showed that mouse hypothalamic GT1-7 cells expressed two bile acid receptors, TGR5 and FXR, whose expressions were regulated by bile acids. Real-time PCR showed that the expression of POMC mRNA was significantly increased in the cells after treatment with 10 μmol/L tLCA or CDCA for 24 h. POMC-derived anorexigenic peptide α-MSH increased significantly in GT1-7 cells after treatment with 10 μmol/L tLCA or CDCA for 24 h. Treatment of the cells with tLCA or CDCA significantly increased the expressions of intracellular signaling proteins including p-STAT3, p-AKT and SOCS3.@*CONCLUSIONS@#Mouse hypothalamic GT1-7 cells express bile acid receptors TGR5 and FXR. Bile acids tLCA or CDCA can promote the expression of POMC mRNA and increase the production of the anorexigenic peptide α-MSH. The intracellular signaling proteins p-AKT, p-STAT3 and SOCS3 are likely involved in bile acid-induced anorexigenic peptide production.

Progress in application of bile acid metabolism in traditional Chinese medicine study / 中国中药杂志

Traditional Chinese medicine boasts aunique theoretical system and rich practical experience. However, traditional Chinese medicine has an unclear material basis, vague pharmacological mechanism, and potential toxicity, which is the key factor to hinder its modernization and wide application. Therefore, when the physico-chemical analysis of chemical components of traditional Chinese medicine is insufficient to reflect the characteristics and mechanisms, the multi-target biological system correlation analysis in conformity to the holistic view of the basic theory of traditional Chinese medicine has gradually attracted wide attention. Specifically, bile acids, as an important endogenous metabolite in the body, play an important role in regulating digestion, absorption and metabolism of nutrients, and greatly impact the health. In recent years, a number of studies have been made on the metabolism pathway of bile acids and their important regulatory effects in body metabolism, making bile acids as a significant target of traditional Chinese medicine on the body. In view of this, based on bile acid metabolism, the paper reviewed the biological functions of bile acids in regulating body metabolism and its interaction with intestinal microbiota, providing a basis for exploring the connotation of bile acid metabolism changes under physiological/pathological conditions of the body. The study progress of bile acid metabolism in traditional Chinese medicine efficacy/toxic mechanism is further reviewed, which provides a basis for exploring the efficacy and hepatotoxicity mechanism of traditional Chinese medicine with bile acid as a biomarker, thereby laying a foundation for the clinical safety of traditional Chinese medicine.