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1.
Front Pharmacol ; 13: 940555, 2022.
Article in English | MEDLINE | ID: mdl-35991874

ABSTRACT

Anemarrhenae Rhizoma (AR) has multiple pharmacological activities to prevent and treat Alzheimer's disease (AD). However, the effect and its molecular mechanism are not elucidated clear. This study aims to evaluate AR's therapeutic effect and mechanism on AD model rats induced by D-galactose and AlCl3 with serum metabolomics. Behavior study, histopathological observations, and biochemical analyses were applied in the AD model assessment. Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-QTOF/MS) were combined with multivariate statistical analysis to identify potential biomarkers of AD and evaluate the therapeutic effect of AR on AD from the perspective of metabolomics. A total of 49 biomarkers associated with the AD model were identified by metabolomics, and pathway analysis was performed to obtain the metabolic pathways closely related to the model. With the pre-treatment of AR, 32 metabolites in the serum of AD model rats were significantly affected by AR compared with the AD model group. The regulated metabolites affected by AR were involved in the pathway of arginine biosynthesis, arginine and proline metabolism, ether lipid metabolism, glutathione metabolism, primary bile acid biosynthesis, and steroid biosynthesis. These multi-platform metabolomics analyses were in accord with the results of behavior study, histopathological observations, and biochemical analyses. This study explored the therapeutic mechanism of AR based on multi-platform metabolomics analyses and provided a scientific basis for the application of AR in the prevention and treatment of AD.

2.
Biomed Res Int ; 2018: 4351674, 2018.
Article in English | MEDLINE | ID: mdl-29546058

ABSTRACT

As one of the most troublesome complications in patients with chronic renal disease, the etiology of uremic pruritus remains unknown, and the current therapeutic approaches are limited and unsatisfactory. To identify potential biomarkers for improving diagnosis and treatment and obtain a better understanding of the pathogenesis of uremic pruritus, we compared serum metabolome profiles of severe uremic pruritus (HUP) patients with mild uremic pruritus (LUP) patients using ultraperformance liquid chromatography-quadruple time-of-flight mass spectrometry (UPLC-QTOF MS). Partial least squares discriminant analysis (PLS-DA) showed that the metabolic profiles of HUP patients are distinguishable from those of LUP patients. Combining multivariate with univariate analysis, 22 significantly different metabolites between HUP and LUP patients were identified. Nine of the 22 metabolites in combination were characterized by a maximum area-under-receiver operating characteristic curve (AUC = 0.899) with a sensitivity of 85.1% and a specificity of 83.0% distinguishing HUP and LUP. Our results indicate that serum metabolome profiling might serve as a promising approach for the diagnosis of uremic pruritus and that the identified biomarkers may improve the understanding of pathophysiology of this disorder. Because the 9 metabolites were phospholipids, uremic toxins, and steroids, further studies may reveal their possible role in the pathogenesis of uremic pruritus.


Subject(s)
Biomarkers/blood , Metabolome , Metabolomics , Pruritus/blood , Adult , Chromatography, High Pressure Liquid , Female , Humans , Male , Middle Aged , Pruritus/pathology , Tandem Mass Spectrometry
3.
J Food Drug Anal ; 26(2): 823-833, 2018 04.
Article in English | MEDLINE | ID: mdl-29567254

ABSTRACT

Rhizoma corydalis and Radix Angelicae Dahurica (Yuanhu-Baizhi) herbal medicine pair has been used for thousands of years and has been reported to be potentially active in recent cancer therapy. But the exact active components or fractions remain unclear. In this study, a new comprehensive two-dimensional (2D) 3-aminopropyltriethoxysilane (APTES)-decorated MCF7-cell membrane chromatography (CMC)/capcell-C18 column/time-of-flight mass spectrometry system was established for screening potential active components and clarifying the active fraction of Yuanhu-Baizhi pair. APTES was modified on the surface of silica, which can provide an amino group to covalently link cell membrane fragments with the help of glutaraldehyde in order to improve the stability and column life span of the MCF7 CMC column. The comprehensive 2D MCF7-CMC system showed good separation and identification abilities. Our screen results showed that the retention components are mainly from the alkaloids in Yuanhu (12 compounds) and the coumarins (10 compounds) in Baizhi, revealing the active fractions of Yuanhu-Baizhi herbal medicine pair. Oxoglaucine, protopine, berberine, osthole, isopimpinellin and palmitic acid were selected as typical components to test the effects on cell proliferation and their IC50 were calculated as 38.17 µM, 29.45 µM, 45.42 µM, 132.7 µM, 156.8 µM and 90.5 µM respectively. Cell apoptosis assay showed that the drug efficacy was obtained mainly through inducing cell apoptosis. Furthermore, a synergistic assay results demonstrated that oxoglaucine (representative of alkaloids from Yuanhu) and isopimpinellin (representative of coumarins from Baizhi) showed significant synergistic efficacy with GFT, indicating that these components may act on other membrane receptors. The proposed 2D CMC system could also be equipped with other cells for further applications. Besides, the follow-up in-vitro experimental strategy using cell proliferation assay, cell apoptosis assay and synergistic assay proved to be a practical way to confirm the active fractions of herbal medicine.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Cell Membrane/drug effects , Chromatography/methods , Corydalis/chemistry , Drugs, Chinese Herbal/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Breast Neoplasms/physiopathology , Cell Membrane/chemistry , Cell Proliferation/drug effects , Drugs, Chinese Herbal/chemistry , Female , Humans , MCF-7 Cells , Mass Spectrometry , Plants, Medicinal/chemistry , Propylamines/chemistry , Rhizome/chemistry , Silanes/chemistry
4.
Chemistry ; 23(45): 10906-10914, 2017 Aug 10.
Article in English | MEDLINE | ID: mdl-28594098

ABSTRACT

Accurate identification of the molecular targets of bioactive small molecules is a highly important yet challenging task in biomedical research. Previously, a method named DPAL (DNA-programmed affinity labeling) for labeling and identifying the cellular targets of small molecules and nucleic acids was developed. Herein, DPAL is applied for the target identification of Alisertib (MLN8237), which is a highly specific aurora kinase A (AKA) inhibitor and a drug candidate being tested in clinical trials for cancer treatment. Apart from the well-established target of AKA, several potential new targets of MLN8237 were identified. Among them, p38 mitogen-activated protein kinase (p38) and laminin receptor (LAMR) were validated to be implicated in the anticancer activities of MLN8237. Interestingly, these new targets were not identified with non-DNA-based affinity probes. This work may facilitate an understanding of the molecular basis of the efficacy and side effects of MLN8237 as a clinical drug candidate. On the other hand, this work has also demonstrated that the method of DPAL could be a useful tool for target identification of bioactive small molecules.


Subject(s)
Azepines/chemistry , DNA/chemistry , Protein Kinase Inhibitors/chemistry , Pyrimidines/chemistry , Affinity Labels , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Aurora Kinase A/antagonists & inhibitors , Aurora Kinase A/metabolism , Azepines/metabolism , Binding Sites , Cell Line , Humans , Molecular Docking Simulation , Protein Kinase Inhibitors/metabolism , Protein Structure, Tertiary , Pyrimidines/metabolism , Receptors, Laminin/antagonists & inhibitors , Receptors, Laminin/metabolism , Surface Plasmon Resonance , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors , p38 Mitogen-Activated Protein Kinases/metabolism
5.
J Pharm Anal ; 4(6): 360-367, 2014 Dec.
Article in English | MEDLINE | ID: mdl-29403901

ABSTRACT

Hyperlipidemia is considered to be a high lipid level in blood, can induce metabolic disorders and dysfunctions of the body, and results in some severe complications. Therefore, hunting for some metabolite markers and clarifying the metabolic pathways in vivo will be an important strategy in the treatment and prevention of hyperlipidemia. In this study, a rat model of hyperlipidemia was constructed according to histopathological data and biochemical parameters, and the metabolites of serum and urine were analyzed by UPLC-Q-TOF/MS. Combining pattern recognition and statistical analysis, 19 candidate biomarkers were screened and identified. These changed metabolites indicated that during the development and progression of hyperlipidemia, energy metabolism, lipid metabolism, amino acid metabolism and nucleotide metabolism were mainly disturbed, which are reported to be closely related to diabetes, cardiovascular diseases, etc. This study demonstrated that a UPLC-Q-TOF/MS based metabolomic approach is useful to profile the alternation of endogenous metabolites of hyperlipidemia.

6.
Yao Xue Xue Bao ; 40(8): 746-9, 2005 Aug.
Article in Chinese | MEDLINE | ID: mdl-16268511

ABSTRACT

AIM: To investigate the stereoselective pharmacokinetic process of tetrahydropalmatine (THP) in rats. METHODS: The concentrations of tetrahydropalmatine enantiomers in rat plasma were determined by coupled achiral and chiral HPLC method. The differences in plasma concentrations and pharmacokinetic parameters between the two enantiomers were compared by paired t-test. RESULTS: The plasma levels of l-THP were always higher than those of d-THP in eight rats. There was significant difference between the main pharmacokinetic parameters of the two enantiomers. CONCLUSION: Tetrahydropalmatine showed significant stereoselective pharmacokinetics in rats after an ig dose of the racemate.


Subject(s)
Berberine Alkaloids/pharmacokinetics , Chromatography, High Pressure Liquid/methods , Animals , Area Under Curve , Berberine Alkaloids/chemistry , Berberine Alkaloids/isolation & purification , Corydalis/chemistry , Female , Male , Molecular Structure , Plants, Medicinal/chemistry , Rats , Rats, Sprague-Dawley , Stereoisomerism
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