Systematic investigation on the chemical basis of anti-NAFLD Qushi Huayu Fang. Part 1: A study of metabolic profiles in vivo and in vitro by high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry.

Qushi Huayu Fang (QHF) is a clinic-empirical prescription for treating non-alcoholic fatty liver disease (NAFLD) in China, which is composed of five herbs. However, the bioactive constituents responsible for the efficacy of QHF remain unclear. Thus, a high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry method was established and adopted to identify the constituents of QHF, and profile its metabolism in vivo and in vitro. Among the 66 constituents in QHF, only 14 compounds of six structural types were absorbed, and 34 metabolites were generated through eight metabolic pathways. A total of 20 metabolites were first reported, including four organic acids, one iridoid, two flavones, five naphthols, three anthraquinones, and five stilbenes. Glucuronidation and sulfation were the main metabolic pathways, and the intestinal metabolism played an important role in the biotransformation of QHF. Many compounds, especially those detected in the liver, the target organ of QHF, were reported to display the anti-NAFLD activity. This is the first study to explore the constituents of QHF and its metabolism in vivo and in vitro, thus realizing the first step to clarify the chemical basis of QHF qualitatively, and laying the foundation for further research on the anti-NAFLD mechanism of QHF.

Correction to: Identifying the active components of Baihe-Zhimu decoction that ameliorate depressive disease by an effective integrated strategy: a systemic pharmacokinetics study combined with classical depression model tests.

[This corrects the article DOI: 10.1186/s13020-019-0254-9.].

Identifying the active components of Baihe-Zhimu decoction that ameliorate depressive disease by an effective integrated strategy: a systemic pharmacokinetics study combined with classical depression model tests.

BACKGROUND: Modern pharmacological studies have demonstrated that Baihe-Zhimu decoction (BZD) has antidepressant effects. However, the complex composition and lack of clear evaluation standards for BZD make it less likely to be understood and accepted than evidence-based active natural compounds. METHODS: In this study, an effective method for the identification of antidepressant components was demonstrated and applied to BZD. The first step was to evaluate the efficacy of BZD by the forced swimming test (FST) and the tail suspension test (TST), followed by successive quantitative analyses of the absorbed constituents at different stages, such as before hepatic disposition, liver distribution, after hepatic disposition and brain distribution after the oral administration of BZD. Finally, the compounds detected in the brain were confirmed by activity testing. RESULTS: Our investigation observed that timosaponin BII and timosaponin BIII were accurately determined in the brain after oral administration of BZD, and they were further confirmed to reduce the immobility time in the FST and TST. As described above, timosaponin BII and timosaponin BIII were used to scientifically and reasonably explain the effective chemical basis of the effect of BZD on depression. CONCLUSIONS: This research affords an effective method to discover lead molecules for antidepressants from traditional Chinese medicine.

Absorption, Metabolism, and Pharmacokinetics Profiles of Norathyriol, an Aglycone of Mangiferin, in Rats by HPLC-MS/MS.

Norathyriol, an aglycone of mangiferin, is a bioactive tetrahydroxyxanthone present in mangosteen and many medicinal plants. However, the biological fate of norathyriol in vivo remains unclear. In this study, the absorption and metabolism of norathyriol in rats were evaluated through HPLC-MS/MS. Results showed that norathyriol was well absorbed, as indicated by its absolute bioavailability of 30.4%. Besides, a total of 21 metabolites of norathyriol were identified in rats, including methylated, glucuronidated, sulfated and glycosylated conjugates, which suggested norathyriol underwent extensive phase II metabolism. Among those metabolites, 15 metabolites were also identified in hepatocytes incubated with norathyriol, indicating the presence of hepatic metabolism. Furthermore, glucuronide and sulfate conjugates, rather than their parent compound, were found to be the main forms existing in vivo after administration of norathyriol, as implicated by the great increase of exposure of norathyriol determined after hydrolysis with ß-glucuronidase and sulfatase. The information obtained from this study contributes to better understanding of the pharmacological mechanism of norathyriol.

Absorption, liver first-pass effect, pharmacokinetics and tissue distribution of calycosin-7-O-ß-d-glucopyranoside (C7G) and its major active metabolite, calycosin, following oral administration of C7G in rats by LC-MS/MS.

Previously, we discovered calycosin, an extensively distributed metabolite of Calycosin-7-O-ß-d-glucopyranoside (C7G), elicited stronger anti-virus activity than C7G. However, the pharmacokinetics and tissue distribution of C7G and calycosin remained obscure on C7G treatments. In this study, a liquid chromatography-tandem mass spectrometry method was established and validated for the simultaneous determination of C7G and calycosin, and it was applied to the pharmacokinetics and tissue distribution of C7G and calycosin following oral administration of C7G at 120mg/kg in rats. Consequently, the exposure of C7G and calycosin was both similarly low in the systemic plasma, but the levels of calycosin were 53.5 folds higher than that of C7G in the portal vein plasma, corresponding to the liver extraction ratio (ER) of C7G and calycosin at 0.3% and 98.5% respectively. Therefore, our results revealed that liver first-pass effect played the predominant role in the poor circulating levels of calycosin on C7G treatments, whereas the intestinal first-pass effect was predominant for those of C7G. In contrast to no observation of C7G, the calycosin levels were 212.1, 30.5 and 4.7 folds higher in the liver, kidney and heart than its circulating levels, respectively. The high tissue distribution of calycosin provided new hints and evidences to the pharmacological mechanisms of C7G and Astragali Radix.