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Simultaneous quantification of 3′,4′-dimethoxy flavonol-3-O-glucoside and its major metabolite in human plasma by LC-MS/MS and its application to a clinical pharmacokinetic study

Article

作者: Chen, Min ; Zhang, Yong ; Zhan, Yan ; Zhong, Dafang ; Li, Xiaoju ; Wang, Lu ; Zhang, Yifan ; Shen, Haifeng

Hyperlipidemia is a disease characterized by abnormal blood lipid levels and is the leading risk factor for cardiovascular disease. 3',4'-Dimethoxy flavonol-3-O-glucoside (abbreviated DF3G) is a new lipid-lowering drug created as a flavonoid structural analog. The principal metabolite of DF3G in human plasma is the aglycone glucuronide conjugate M2. The purpose of this study is to use liquid chromatography-tandem mass spectrometry to develop and validate a quantitative analysis method for DF3G and its metabolite M2 in human plasma, and to use the method to investigate the pharmacokinetics of DF3G and M2 in a clinical trial. This method employed DF3G-d₆ as the internal standard, and plasma samples were processed by protein precipitation. Isocratic separation could accurately differentiate DF3G, M2, and DF3G-d₆ from endogenous components in the matrix or other components in the samples, and endogenous components in the matrix had little impact on ionization efficiency. Positive electrospray ionization with multiple reaction monitoring (MRM) transitions of m/z 461.2 → 299.0 for DF3G, m/z 475.1 → 299.1 for M2 and m/z 467.1 → 305.1 for DF3G-d₆ was used for quantification. The DF3G and M2 linear range for plasma were in the range of 4.00/4.00 ng/mL to 4000/4000 ng/mL. Both the analytes and the internal standard were stable regardless of whether they were in solution or plasma samples. The accuracy of the average concentration of the quality control samples was within 15% of the theoretical value, and the RSD was less than 15%. The method is rapid, accurate, straightforward, and precise. It is appropriate for the determination of DF3G and M2 concentrations in human plasma and has been successfully applied to determine the pharmacokinetic analysis in phase I clinical trials.

Yaoxue Shijian Zazhi

Comparative study on volatile oil in Rhizoma chuanxiong by steam distillation and supercritical fluid extraction

作者: Deng Peng ; Chen Shan ; Wei Feixue ; Wen Yi ; Wang Baoyi

Objective To clarify the influence of the extraction process on its active ingredients by comparing the volatile oils of Rhizoma Chuanxiong obtained under different processes.Methods The volatile oil of Rhizoma Chuanxiong was extracted by supercritical CO_2 extraction(SFE) and steam distillationThe main chem. components and relative contents were identified by gas chromatog.-mass spectrometry(GC-MS).Results A total of 18 common components were identified in the volatile oil samples of Chuanxiong from the two methods.In steam distillation samples, main components included phthalides(61%),monoterpenoids(25%) and sesquiterpenes(10%).In SFE samples, phthalides(97%) were major components, followed by monoterpenoids(1%),sesquiterpenes(0.4%) and other minor components.Conclusion The steam distillation retains highly volatile components in Rhizoma chuanxiong such as monoterpenoids and sesquiterpenes.For SFE approach, the phthalides were extracted more efficiently compared with other components.The effect of the extraction process on the active ingredients should be fully considered in obtained products of Rhizoma chuanxiong since the difference in constituents may result in varied effects.

Frontiers in Pharmacology2区 · 医学

Ginger Alleviates DSS-Induced Ulcerative Colitis Severity by Improving the Diversity and Function of Gut Microbiota

2区 · 医学

ArticleOA

作者: Huang, Jinghua ; Wang, Shuocun ; Chen, Shan ; Pang, Xiaobin ; Lu, Yiming ; Wang, Li ; Xiong, Liyan ; Wang, Tingfang ; Guo, Shanshan ; Rong, Xuli ; Geng, Wenye

The effects of ginger on gastrointestinal disorders such as ulcerative colitis have been widely investigated using experimental models; however, the mechanisms underlying its therapeutic actions are still unknown. In this study, we investigated the correlation between the therapeutic effects of ginger and the regulation of the gut microbiota. We used dextran sulfate sodium (DSS) to induce colitis and found that ginger alleviated colitis-associated pathological changes and decreased the mRNA expression levels of interleukin-6 and inducible nitric oxide synthase in mice. 16s rRNA sequencing analysis of the feces samples showed that mice with colitis had an intestinal flora imbalance with lower species diversity and richness. At the phylum level, a higher abundance of pathogenic bacteria, Proteobacteria and firmicutes, were observed; at the genus level, most samples in the model group showed an increase in Lachnospiraceae_NK4A136_group. The overall analysis illustrated an increase in the relative abundance of Lactobacillus_murinus, Lachnospiraceae_bacterium_615, and Ruminiclostridium_sp._KB18. These increased pathogenic bacteria in model mice were decreased when treated with ginger. DSS-treated mice showed a lower abundance of Muribaculaceae, and ginger corrected this disorder. The bacterial community structure of the ginger group analyzed with Alpha and Beta indices was similar to that of the control group. The results also illustrated that altered intestinal microbiomes affected physiological functions and adjusted key metabolic pathways in mice. In conclusion, this research presented that ginger reduced DSS-induced colitis severity and positively regulated the intestinal microbiome. Based on the series of data in this study, we hypothesize that ginger can improve diseases by restoring the diversity and functions of the gut microbiota.

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