Metabolic profiling of endogenous bile acids: a novel method to assess hepatoprotective effect of Tanreqing capsule on carbon-tetrachloride-induced liver injury in rats.

Tanreqing (TRQ), a traditional Chinese medicine (TCM) formula, can alleviate liver injury and improve liver function. Its pharmacological mechanisms of actions are still unclear due to its complex components and multi-target natures. Metabolomic study is an effective approach to investigating drug pharmacological actions, new diagnostic markers, and potential mechanisms of actions. In the present study, a new strategy was used to evaluate the protective effect of TRQ capsule against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats, by analyzing metabolic profiling of endogenous bile acids (BAs) along with biochemical and histological analyses. BAs concentrations were determined by ultra-performance liquid chromatography coupled with quadrupole mass spectrometry (UPLC-MS). Principal component analysis and partial least squares discriminant analysis were then employed to analyze the UPLC-MS results and compare the hepatoprotective effect of TRQ capsule in different groups at the doses of 0.36, 1.44, and 2.88 g·kg-1 body weight, respectively. Moreover, our results suggested that taurocholic acid (TCA) and taurohyodesoxycholic acid (THDCA) were the most important biochemical markers, which were indicative of CCl4-induced acute hepatic damage and hepatoprotective effect of TRQ capsule. Therefore, this new strategy would be an excellent alternative method for evaluating hepatoprotective effect and proposing potential mechanisms of action for other drugs as well.

Simultaneous quantification of chlorogenic acid and taurocholic acid in human plasma by LC-MS/MS and its application to a pharmacokinetic study after oral administration of Shuanghua Baihe tablets.

An LC-MS/MS method was developed and validated for the simultaneous quantification of chlorogenic acid (CGA) and taurocholic acid (TCA) in human plasma using hydrochlorothiazide as the internal standard. The chromatographic separation was achieved on a Hedera ODS-2 column with a gradient elution using 10 mmol·L(-1) of ammonium acetate buffer solution containing 0.5% of formic acid - acetonitrile as mobile phase at a flow rate of 300 µL·min(-1). The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring in negative ESI mode. The method was fully validated over the concentration ranges of 0.1-10 ng·mL(-1) for CGA and 2-150 ng·mL(-1) for TCA. It was successfully applied to a pharmacokinetic study of CGA and TCA in healthy Chinese volunteers after oral administration of Shuanghua Baihe tablets (SBTs). In the single-dose study, the maximum plasma concentration (Cmax), time to reach Cmax (Tmax) and elimination half-life (t1/2) of CGA were (0.763 8 ± 0.542 0) ng·mL(-1), (1.0 ± 0.5) h, and (1.3 ± 0.6) h, respectively. In the multiple-dose study, the Cmax, Tmax and t1/2 of CGA were (0.663 7 ± 0.583 3) ng·mL(-1), (1.1 ± 0.5) h, and (1.4 ± 0.7) h, respectively. For TCA, no significant characteristic increasing plasma TCA concentration-time curve was found in the volunteers after oral administration of SBTs, indicating its complicated process in vivo as an endogenous ingredient.

Lipidomic and metabolomic analyses reveal potential plasma biomarkers of early atheromatous plaque formation in hamsters.

AIMS: Atherosclerosis is the main pathological process contributing to cardiovascular disease, with diet being the most important factor involved. Although the lipidome of atheromatous plaque has been studied previously, the use of comparative lipidomics and metabolomics in plasma in early atherogenesis could lead to the discovery of plasma biomarkers that allow not only disease prediction but also measurement of disease progression. METHODS AND RESULTS: High-throughput techniques, such as liquid chromatography/mass spectrometry, allowed us to compare the circulating and aortic lipidome and plasma metabolome in order to look for new molecular targets involved in atherogenesis. To achieve this objective, we chose the hamster (Mesocricetus auratus) as the best small animal model for diet-induced early atherosclerosis, because its lipoprotein metabolism is similar to that of humans. The results revealed the existence of several, previously unreported, changes in lipid and amino-acid metabolism, the peroxisome proliferator-activated receptor γ pathway, and oxidative and endoplasmic reticulum stress, also involving cell senescence. Furthermore, as a proof of concept in the modelling of dietary influences in atherogenesis, we have measured the effect of a potential anti-atherogenic polyphenol extract on the reported pathways. Our results support a previously unknown role for taurocholic acid as a potential plasma biomarker of early atheromatous plaque formation. CONCLUSION: The use of comparative liquid chromatography/mass spectrometry-based lipidomics and metabolomics allows the discovery of novel pathways in atherogenesis, as well as new potential plasma biomarkers, which could allow us to predict disease in its early stages and measure its progression.

Influence of dietary taurine on vitamin D absorption.

To evaluate the influence of dietary taurine supplementation on vitamin D absorption, we studied three groups of infants: 21 (11 preterm) were fed a taurine-free formula, 21 (10 preterm) were fed a taurine-supplemented formula (50 mg/100 g of powder) and 20 (9 preterm) were fed human, not heat-treated milk. Taurine, total bile acids, glyco-(GBA) and tauro-(TBA) conjugated bile acids, 25-hydroxyvitamin D3 (25OHD3) and 1,25-dihydroxyvitamin D3 (1,25OH2D3) were determined in all infants at birth in blood cord and at one and three months of life. In preterm infants fed a taurine-free formula, we found lower plasma taurine levels than in infants of other groups at one and three months of life. In these infants, GBA predominated, with a G/T ratio of 1.1 and 1.4 at one and three months of life, whereas in all other infants TBA predominated with a G/T ratio always < 1. Also, 25OHD3 and 1,25OH2D3 levels were significantly lower in preterm infants fed a taurine-free formula than in infants fed a taurine-enriched formula or human milk. Term infants fed a taurine-free formula did not show differences in the parameters studied in comparison to infants of other groups. Low taurine dietary intake appears to compromise vitamin D absorption in preterm infants, and therefore taurine supplementation of preterm infant formulas should be encouraged.