Meicun Yao

Design, synthesis, and evaluation of resveratrol derivatives as Aß1–42 aggregation inhibitors, antioxidants, and neuroprotective agents

A series of novel resveratrol derivatives were designed, synthesised and evaluated as potential therapeutic agents for the treatment of Alzheimers disease. Among these compounds, compound 7l, (E)-5-(4-(isopropylamino)styryl)benzene-1,3-diol, exhibited potent ß-amyloid aggregation inhibition activity, which was confirmed by a ThT fluorescence assay (71.65% at 20 μM) and transmission electron microscopy (TEM). Compound 7l also exhibited good antioxidant activity (4.12 Trolox equivalents in an oxygen radical absorbance capacity assay and a 37% reduction in reactive oxygen species in cells at 10 μM). The cytotoxicity analysis of compounds 7f, 7i, 7j and 7l indicated that these compounds have lower toxicities than resveratrol at 60 μM.

Analysis of Essential Oils from Cassia Bark and Cassia Twig Samples by GC-MS Combined with Multivariate Data Analysis

Cinnamomum cassia is one of several species of Cinnamomum which has been widely used as a spice. In this study, the chemical profiles of its bark and twig were characterized by gas chromatography-mass spectrometry (GC-MS) and multivariate data analysis. Principle component analysis (PCA) and orthogonal projection to latent structures discriminate analysis (OPLS-DA) of GC-MS data provided a clear separation between those samples. The result obviously showed that the metabolome of cinnamon bark (CB) and cinnamon twig (CT) is different, and the corresponding loading S-plots revealed that the differential metabolites between the essential oils of CB and CT were trans-cinnamaldehyde, trans-anethole, α-cubebene, γ-muurolene, γ-amorphene, δ-cadinene, (−)-calamenene, and o-methoxycinnamaldehyde. Our study demonstrates that the combination of GC-MS spectrum and multivariate data analysis can be applied to identify essential oils from different parts of C. cassia.

A strategy for the targeted metabolomics analysis of 11 gut microbiota-host co-metabolites in rat serum, urine and feces by ultra high performance liquid chromatography–tandem mass spectrometry

Microbiota-host co-metabolites are well-known to play important physiological roles, and their dysregulation has been found to be closely related to various diseases, including but not limited to inflammatory disorders. We developed herein an original and feasible method using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The method developed enables rapid quantification of 11 key gut microbiota-host co-metabolites spanning the succinate, phenylacetylglutamine, hippurate and trimethylamine metabolic pathways within 10 min. With this method, we were able to simultaneously monitor inflammation-induced alterations of these metabolites in rat serum, urine and feces matrices. The measured levels for this panel of endogenous metabolites ranged from 0.001 to 172.8 μg m L(-1). The intra- and inter-day precision of three analytes was less than 13.1% and the accuracy was between -13.0 to 11.2% for all QC levels. The extraction recoveries in serum ranged from 85.4 to 103.2%, while the RSD was 9.0% or less for all recoveries. In addition, extraction recoveries of 11 analytes in urine and feces samples were between 85.7% and 102.0% and RSD was less than 9.5%. The method developed here has been successfully applied to the analysis of real samples from 2,4,6-trinitrobenzenesulfonic acid-induced Crohns disease in rats. All of these results suggest that the presently developed method is sufficiently sensitive and robust to simultaneously monitor co-metabolites with diverse properties and a range of different concentrations. Therefore, this method will be expected to be useful for comprehensive studies of the pathophysiological roles and mechanisms of these key microbiota-host co-metabolites, which reflect the function of the intestine, consequently offering novel opportunities for evaluating the occurrence, development and therapeutic effects of diseases related to microbiota disturbances.

Effect of natural borneol on the pharmacokinetics and distribution of nimodipine in mice

The purpose of this study was to investigate the effect of natural borneol (NB) on the pharmacokinetics and distribution of nimodipine in mice. A single dose of nimodipine was administered intravenously (2xa0mg/kg) to mice pretreated with NB (250xa0mg/kg) or vehicle. Blood as well as brain, liver, and kidney tissue samples were collected at 5, 10, 20, 40, and 60xa0min post-dose nimodipine. The concentrations of nimodipine in plasma and tissues were determined by ultra performance liquid chromatography (UPLC) coupled with UV detection, and the pharmacokinetic parameters were calculated based on non-compartmental analysis. NB increased the plasma AUC5–60 min by 26xa0% compared to the vehicle. In addition, brain concentrations of nimodipine in NB-treated mice were significantly higher than those in control mice with the increased AUC5–60 min by 30xa0%. In liver and kidney, NB also caused 26 and 47xa0% increase in AUC5–60 min, respectively. These results implicated that NB may inhibit the metabolism or elimination of nimodipine and enhance its distribution in brain and kidney tissue.

Systematic study on QAMS method for simultaneous determination of triterpenoid saponins in Ilex pubescens by HPLC and UPLC

The quantitative analysis of multi-components with single marker (QAMS) method was firstly established for simultaneous determination of six triterpenoid saponins (ilexgenin A (C1), ilexsaponin A1 (C2), ilexsaponin B1 (C3), ilexsaponin B2 (C4), ilexsaponin B3 (DC1), ilexoside O (DC2)) in Ilex pubescens by Ultra Performance Liquid Chromatography (UPLC) and High Performance Liquid Chromatography (HPLC). Using C1 as the internal reference, the relative correction factors (RCF) of the other five triterpenoid saponins were calculated and statistically evaluated. The durability of the method was verified with five different LC instruments and five different C18 columns under various chromatographic conditions. The external standard method after methodology verification was chosen to check the accuracy and feasibility of the QAMS method. The results showed that the RCFs of all compounds were obtained with good reproducibility (RSD < 5.0%), whether on different chromatography instruments or under various chromatographic conditions. The relative retention value method could be adopted for accurately positioning the chromatographic peak of the six constituents, with their values of RSD ranging between 0.5% and 1.6%. Meanwhile, no significant differences were found in the quantitative results of the six saponins in nine batches of medicines calculated by the QAMS method and external standard method, whether on a HPLC system or UPLC system. The QAMS method established in our research for simultaneous determination of the six saponins is accurate and can be feasibly used to evaluate the quality of Ilex pubescens, especially when the standard substance is inconvenient to obtain.

Comparative pharmacokinetic and tissue distribution study of baicalin, baicalein, wogonoside, wogonin and oroxylin-A after oral administration of Component compatibility of SHT and total flavonoids fractions of Radix scutellariae to rats

Sanwu-Huangqin-Tang (SHT) is a classical prescription used for treatment of gynecological disease, and its key ingredient is Radix scutellariae (Scutellaria baicalensis Georgi, Labiatae). Baicalin, wogonoside, baicalein, wogonin and oroxylin-A are five main effective ingredients enriched in Radix scutellariae. In the present study, pharmacokinetic and tissue distribution difference of the five compounds following oral administration of Component Compatibility of Sanwu-Huangqin-Tang (CCSHT) and total flavonoids fractions of Radix scutellariae (FSR) were investigated in male Sprague-Dawley rats with approximately the same dose. The amount of flavonoids in plasma and tissues were measured by a rapid and sensitive HPLC-MS/MS method. Unpaired Students-test was used for statistical comparison. The bimodal phenomenon was observed in plasma profile after oral administration of FSR and CCSHT. Statistical significant increase (P < 0.05) in pharmacokinetic parameters (including Cmax and AUC0→t) and tissue distribution of the target compounds were observed after oral administration CCSHT comparing with FSR, but there were no significant differences between the two groups in parameters of Tmax. The results indicated that compared with FSR, the bioavailability and distribution amount of flavonoids could be greatly improved by co-administrating alkaloids in Radix sophorae flavescentis and polysaccharide in Radix Scutellariae.

A Systems Pharmacology Approach to Determine Active Compounds and Action Mechanisms of Xipayi KuiJie’an enema for Treatment of Ulcerative colitis

Xipayi Kui Jie’an (KJA), a type of traditional Uygur medicine (TUM), has shown promising therapeutic effects in Ulcerative colitis (UC). Owing to the complexity of TUM, the pharmacological mechanism of KJA remains vague. Therefore, the identification of complex molecular mechanisms is a major challenge and a new method is urgently needed to address this problem. In this study, we established a feasible pharmacological model based on systems pharmacology to identify potential compounds and targets. We also applied compound-target and target-diseases network analysis to evaluate the action mechanisms. According to the predicted results, 12 active compounds were selected and these compounds were also identified by HPLC-ESI-MS/MS analysis. The main components were tannins, this result is consistent with the prediction. The active compounds interacted with 22 targets. Two targets including PTGS2 and PPARG were demonstrated to be the main targets associated with UC. Systematic analysis of the constructed networks revealed that these targets were mainly involved in NF-κB signaling pathway. Furthermore, KJA could also regulate the CD4u2009+u2009CD25u2009+u2009Foxp3u2009+u2009Treg cells. In conclusion, this systems pharmacology-based approach not only explained that KJA could alleviate the UC by regulating its candidate targets, but also gave new insights into the potential novel therapeutic strategies for UC.

Dynamic metabonomic and microbiological response of rats to lincomycin exposure: an integrated microbiology and metabonomics analysis

Humans are associated with a consortium of gut microbiome and individual variations in the microbes influence host metabolism. To probe the relationship between microbiome and the host metabolic changes, we analyzed the metabonomic and microbiological response of rats exposed to lincomycin (LM) by an integrated approach combining 16S rRNA gene sequencing and 1H NMR-based metabolomics profiling. LM exposure resulted in decreased levels of hippurate, short chain fatty acids (SCFAs) and primary bile acids and increased levels of choline and oligosaccharides. Levels of Barnesiella and Prevotella decreased sharply, whereas level of Clostridium cluster XIVa increased slightly. In addition, strong correlations were observed between metabolites and the levels of Barnesiella, Prevotella and Escherichia coli. Meanwhile, some metabolites, such as N-methylnicotinate and trigonelline, showed association with osmotic homeostasis and nucleic acid synthesis. These results suggest that LM exposure lead to significantly suppressed fermentation, gut microbial modification of bile acids and influenced liver and kidney homeostasis. This applicable method reveals the effects regarding metabonomic and microbiological responses of LM, and the combination of microbiology and metabonomics as a powerful approach offers a non-invasive means to elucidate the progression of drugs and diet. The correlation between the host and gut microbiota identifies potential biomarkers and provides substantial insight into the bacterial function, which in turn could provide a rationale for development of potential microbiota-based early prevention and therapeutic interventions.

An integrated metabonomics and microbiology analysis of host-microbiota metabolic interactions in rats with Coptis chinensis-induced diarrhea

Coptis chinensis Franch., a bererine-containing traditional Chinese medicine (TCM), is often used to treat intestinal infections, diabetes and hyperlipidaemia, and often causes diarrhea. To clarify the potential mechanism of toxicity that induces diarrhea, Sprague-Dawley (SD) rats were treated with Coptis chinensis dosage of 5 g kg−1 for 14 consecutive days. PCR-denaturing gradient gel electrophoresis (PCR-DGGE) was used to monitor the dynamic changes in the gut microbiota, while 1H NMR profiles were applied to reveal the metabolism of host and microflora. In the Coptis chinensis-treated group, decreased short chain fatty acids (SCFAs) and branched chain fatty acids (BCFAs) and increased branched chain amino acids (BCAAs) levels were detected in faeces, whereas increased BCFAs were present in the urine. This finding implied that Coptis chinensis triggered malabsorption and suppressed bacterial fermentation as well as protein degradation. Meanwhile, decreased levels of Bacteroides and Prevotella and elevated levels of Enterobacter and Veillonella in the treatment group were significantly correlated to the urinary and faecal metabolites. Using metabolite-set enrichment analysis (MSEA) and the correlation analysis between significant bacteria and metabolites, the results demonstrated that Coptis chinensis intervention suppressed glycine and serine metabolism which affected the growth of intestinal bacteria. Moreover, the perturbed microbiome consequently influenced the homeostasis of monosaccharides, amino acids, and choline, and energy metabolism of gut microbiota and host. These findings help to elucidate Coptis chinensis intervention and toxicity; simultaneously, this integrated strategy may provide an effective method for the systematic assessment of host responses to TCM or any other botanical-based nutraceuticals.

Simultaneous Quantification of Limonin, Two Indolequinazoline Alkaloids, and Four Quinolone Alkaloids in Evodia rutaecarpa (Juss.) Benth by HPLC-DAD Method

A simple and efficient HPLC-DAD (225u2009nm) method was developed and validated for the simultaneous determination of limonin and six key alkaloids (evodiamine, rutaecarpine, 1-methyl-2-undecyl-4(1H)-quinolone, evocarpine, 1-methy-2-[(6Z,9Z)]-6,9-pentadecadienyl-4-(1H)-quinolone, and dihydroevocarpine) in Evodia rutaecarpa (Juss.) Benth, which has been widely used as one of the Traditional Chinese Medicines. The chromatographic separation was carried out on a Hypersil BDS C18 column, and gradient elution was employed with a mobile phase containing acetonitrile and water. Contents of the analytes in 18 batches of samples were analyzed by ultrasonic extraction with ethanol and water mixture (80u2009:u200920, v/v) followed by HPLC analysis. Separation of the seven analytes was achieved within 60u2009min with good linearity (r > 0.999). The RSD of both the intraday and interday precision was below 1.85%. The accuracy at different concentrations was within the range of 97.91 to 100.49%. Hierarchical clustering analysis was performed to differentiate and classify the samples based on the contents of the seven constituents. This study indicated that the quality control of E. rutaecarpa could be simplified to the measurement of four constituents, and that limonin, 1-methyl-2-undecyl-4(1H)-quinolone, and dihydroevocarpine should also be served as the chemical markers together with evodiamine for the quality control of Evodia rutaecarpa (Juss.) Benth.