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Biomedical Chromatography-09 November 2018
Pharmacokinetics and tissue distribution study of bisabolangelone from Angelicae Pubescentis Radix in rat using LC–MS/MS期刊名:Biomedical Chromatography文献编号:DOI 10.1002/bmc.4433文献地址:https://onlinelibrary.wiley.com/doi/abs/10.1002/bmc.4433发表日期:09 November 2018
AbstractA sensitive and accurate LC–MS/MS method was established for quantifying bisabolangelone in rat plasma and tissues. Bisabolangelone was isolated and purified from Angelicae Pubescentis Radix. The pharmacokinetic and tissue distribution of bisabolangelone after administration to rat was performed by LC–MS/MS. Separation was carried out on a C8 (4.6 × 100 mm, 1.8 μm) column. The MS/MS transitions of bisabolangelone and tussilagone (internal standard) were set at m/z 249.1 → 109.1 and m/z 391.4 → 217.4, respectively. The lower limit of quantification in plasma and other tissues ranged from 1 to 4 ng/mL. The biosamples were prepared using protein precipitation method with acetonitrile. The recovery was >92%. The results showed that values of maximum concentrations and area under the curve depended linearly on the studied doses (2.5, 5 and 7.5 mg/kg body weight). The other ingredients in Angelicae Pubescentis Radix extract possibly reduce the absorption of bisabolangelone in rat. Tissue distribution revealed that bisabolangelone was widely distributed in vivo. The highest and lowest concentrations of bisabolangelone were found in the stomach and in the brain, respectively. It was concluded that the newly established HPLC–MS/MS method was suitable to describe the pharmacokinetic characteristics of bisabolangelone in rat after administrationTussilagone [internal standard (IS), purity > 98.9%] was purchased from Chengdu Desite Biological Technology Co., Ltd (Chengdu, China)
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CircSV2b participates in oxidative stress regulation through miR-5107-5p-Foxk1-Akt1 axis in Parkinson's disease
As a novel type of non-coding RNAs, covalently closed circular RNAs (circRNAs) are ubiquitously expressed in eukaryotes. Emerging studies have indicated that dysregulation of circRNAs was related to neurological diseases. However, the biogenesis, regulation, function, and mechanism of circRNAs in Parkinson's disease (PD) remain largely unclear. In this study, thirty-three differentially expressed circRNAs (DECs) were detected by RNA-sequencing between the MPTP-induced PD mice model and the wild-type mice. Quantitative real-time PCR was used to determine the RNA level of DECs in the striatum (STR), substantia nigra pars compacta (SNpc), and serum exosomes, and it was found that circSV2b was downregulated in PD mice. Then, functional experiments in vivo were employed to explore the effect of circSV2b in PD. For the mechanism study, dual-luciferase reporter, fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP),RNA pull-down, gene editing, and CUT & Tag were performed in vitro to confirm that circSV2b directly sponged miR-5107-5p and alleviated the suppression of the expression of the target gene Foxk1, and then positively regulated Akt1 transcription.In vivo, the mechanistic analysis demonstrated that circSV2b overexpression resisted oxidative stress damage through the ceRNA-Akt1 axis in PD models. Taken together,these findings suggested that the miR-5107-5p-Foxk1-Akt1 axis might serve as a key target of circSV2b overexpression in PD treatment, and highlighted the significant change of circSV2b in serum exosomes. Therefore, circSV2b might be a novel biomarker for the diagnosis and treatment of PD.
Keywords: circSV2b, miR-5107-5p, Foxk1, Akt1, oxidative stress
High Pressure Liquid Chromatography (HPLC) Detection
Mice in each group were sacrificed and their brains were rapidly removed......To quantify the sample peaks, each chemical was compared to external standards (DA hydrochloride, DD0177; DOPAC, DE0034; HVA, DG0021. Desite, Chengdu, China)
文献地址:https://doi.org/10.1016/j.redox.2022.102430
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Characterization of prenylated phenolics in Glycyrrhiza uralensis by offline two-dimensional liquid chromatography/mass spectrometry coupled with mass defect filter
Prenylated phenolics are an important class of natural products. In this study, an efficient strategy was estab-lished to systematically characterize the prenylated phenolics in Glycyrrhiza uralensis, a popular herbal medicine. Firstly, offline two-dimensional liquid chromatography/mass spectrometry (2DLC/MS) coupled with mass defect filter (MDF) technology was used to preliminarily detect 1631 potential prenylated phenolics. Secondly, the tandem mass spectrometry fragmentation features of different types of prenylated phenolics were investigated using 29 reference standards. Diagnostic fragmentations included neutral loss (NL) of 42 Da for the annular type and NL of 56 Da for the catenulate type in the positive ion mode, and NL of 56 Da for A-ring prenyl groups and NL of 69 Da for B-ring prenyl groups in the negative ion mode. As a result, the prenylation types, substitution sites, and adjacent OH and OCH3 substitutions of 320 prenylated phenolics in G. uralensis were rapidly char-acterized. Moreover, three prenylated dihydrostilbenes were purified from the aerial part of G. uralensis to verify the structural characterizations.
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The 66 reference standards used in this study were isolated from licorice or purchased from DeSiTe Biological Technology Co., Ltd. (Chengdu,China)
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原文地址:https://doi.org/10.1016/j.jpba.2022.115009
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European Journal of Drug Metabolism and Pharmacokinetics
The Influence of Compatibility of Rhubarb and Radix Scutellariae on the Pharmacokinetics of Anthraquinones and Flavonoids in Rat Plasma期刊名:European Journal of Drug Metabolism and Pharmacokinetics文献编号:DOI 10.1007/s13318-017-0444-8文献地址:https://link.springer.com/article/10.1007%2Fs13318-017-0444-8发表日期:14 November 2017
Abstract
Background and Objectives
Rhubarb–Radix scutellariae is a classic herb pair, which is commonly used to clear away heat and toxin in clinic. The aim of this study was to investigate the influence of compatibility of Rhubarb and Radix scutellariae on the pharmacokinetic behaviors of anthraquinones and flavonoids in rat plasma.
Methods
Eighteen rats were randomly divided into three groups, and were orally administered Rhubarb and/or Radix scutellariae extracts. A sensitive and rapid UPLC–MS/MS method was developed and validated to determine the concentrations of baicalin, baicalein, wogonside, wogonin, rhein, and emodin in rat plasma. The concentrations of phase II conjugates of flavonoid aglycones and anthraquinone aglycones were also determined after hydrolyzing the plasma with sulfatase.
Results
Compared with administration of Radix scutellariae alone, co-administration of Rhubarb significantly decreased the first maximum plasma concentration (C max1) of baicalin, wogonside, and the phase II conjugates of baicalein, wogonin to 46.40, 61.27, 41.49, and 20.50%, respectively. The area under the plasma concentration–time curve from time zero to infinity (AUC0–∞) was significantly decreased from 82.60 ± 20.22 to 51.91 ± 7.46 μM·h for rhein and 276.83 ± 98.02 to 175.42 ± 86.82 μM·h for the phase II conjugates of wogonin after compatibility. The time to reach the first maximum plasma concentration (T max1) of anthraquinones was shortened and the second peak of anthraquinones disappeared after compatibility.
Conclusions
Compatibility of Rhubarb and Radix scutellariae can significantly affect the pharmacokinetic behaviors of characteristic constituents of the two herbs. The cause of these pharmacokinetic differences was further discussed combined with the in vivo ADME (absorption, disposition, metabolism, and excretion) processes of anthraquinones and flavonoids.Rhein (R), emodin (E), baicalin (BG), baicalein (B), wogonside (WG), and wogonin (W) standards were purchased from Chengdu Desite Biological Technology Co., Ltd. (Sichuan, China).
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Journal of separation science-03 March 2019
Ionic liquid vortex-simplified matrix solid-phase dispersion for the simultaneous determination of terpenoids, crocins, quinic acid derivatives and flavonoids in Gardeniae fructus by UHPLC期刊名:Journal of separation science文献编号:DOI 10.1002/jssc.201801354文献地址:https://onlinelibrary.wiley.com/doi/abs/10.1002/jssc.201801354发表日期:03 March 2019AbstractA novel ionic‐liquid‐based vortex‐simplified matrix solid‐phase dispersion method using 2,6‐dimethyl‐β‐cyclodextrin was established by ultra high performance liquid chromatography coupled with a photodiode array detector. 2,6‐Dimethyl‐β‐cyclodextrin was first used as a promising adsorbent in this proposed method for simultaneous determination of eight compounds in Gardeniae fructus. These compounds are terpenoids (geniposidic acid, genipin‐1‐β‐D‐gentiobioside, geniposide, 8‐o‐acetyl shanzhiside methyl ester), crocins (crocin‐I, crocin‐II), quinic acid derivatives (chlorogenic acid), and flavonoids (isoquercitrin), respectively. Several parameters were investigated in the adsorption and desorption processes to obtain the optimal conditions, including 2,6‐dimethyl‐β‐cyclodextrin as sorbent, 0.5 mL 100 mM 1‐dodecyl‐3‐methylimidazolium hydrogen sulfate as the extraction solvent, 2:1 of sample/sorbent ratio, grinding for 2 min and vortexing for 60 s. The recoveries of the eight compounds ranged from 96.6 to 100% (<3.50%). The limits of detection and quantification were in the range of 0.02–0.30 and 0.06–1.25 μg/mL, respectively. Meanwhile, a good linearity was attained with r values (>0.9997). The established method showed higher extraction efficiency and less reagent consumption than traditional matrix solid phase dispersion and ultrasonic‐assisted extraction. Hence, it could be applied for sample preparation and analysis of natural products.Standard substances including geniposidic acid, chlorogenic acid, genipin-1-β-Dgentiobioside, geniposide, 8-o-acetyshanzhiside methyl ester, isoquercitrin, crocin I, and crocin II were purchased from Chengdu Desite Biological Technology Co., Ltd(Chengdu, China).
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Biomedical Chromatography-29 May 2018
Tissue distribution study of periplocin and its two metabolites in rats by a validated LC-MS/MS method期刊名:Biomedical Chromatography文献编号:DOI 10.1002/bmc.4302文献地址:https://link.springer.com/article/10.1007%2Fs13318-017-0444-8发表日期:29 May 2018AbstractPeriplocin is a cardiac glycoside and has been used widely in the clinic for its cardiotonic, anti‐inflammatory and anti‐tumor effects. Although it is taken frequently by oral administration in the clinic, there have been no reports demonstrating that periplocin could be detected in vivo after an oral administration, so there is an urgen need to determine the characteristics of periplocin in vivo after oral administration. In this study, a sensitive and reliable liquid chromatography–tandem mass spectrometry method was developed and validated to identify and quantify periplocin and its two metabolites in rat tissue after a single dosage of perplocin at 50 mg/kg. The results demonstrated that periplocin and its two metabolites were detected in all of the selected tissues; periplocin could reach peak concentration quickly after administration, while periplocymarin and periplogenin reached maximum concentration > 4.83 h after administration. The tissue distribution of analytes tended to be mostly in the liver, and higher analyte concentrations were found in the heart, liver, spleen, lung and kidney, but a small amount of chemical constituents was distributed into the brain. The consequences obtained using this method might provide a meaningful insight for clinical investigations and applications.Periplocymarin (≥ 98 %), periplogenin (≥ 98 %) were obtained from Chengdu Desite Biological Technology Co., Ltd(Chengdu, China)
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