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1.
Food Chem ; 289: 419-425, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-30955632

RESUMO

Surface plasmon resonance (SPR) analysis of the main components of liquorice was performed and a novel strong mineralocorticoid receptor (MR) agonist, namely liquiritinapioside (LA), whose the binding constant was 1.093 × 10-5 M, was reported. As a supplement, LA has been further demonstrated to have a strong MR binding capacity through competitive binding experiments (the enrichment factor of LA was 10.22%). This study also validated the activity of LA on H9c2 cells. The expression of collagen I and the results of Masson staining were used to determine the ability of this substance to cause H9c2 cell fibrosis. Moreover, western blotting was used to verify the mechanism of compound-induced myocardial fibrosis. Overall, the attained results showed that LA could induce the activation of the TGF-ß1/p38 MAPK signalling pathway through the MR to induce H9c2 cell fibrosis.


Assuntos
Glycyrrhiza/efeitos adversos , Glycyrrhiza/química , Mineralocorticoides , Receptores de Mineralocorticoides/agonistas , Animais , Linhagem Celular , China , Colágeno Tipo I/metabolismo , Fibrose , Flavanonas/efeitos adversos , Flavanonas/análise , Flavanonas/metabolismo , Glucosídeos/efeitos adversos , Glucosídeos/análise , Glucosídeos/metabolismo , Glycyrrhiza/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Miocárdio/patologia , Extratos Vegetais/química , Receptores de Mineralocorticoides/metabolismo , Transdução de Sinais/efeitos dos fármacos , Terpenos , Fator de Crescimento Transformador beta1/metabolismo
2.
Toxicol Res (Camb) ; 7(6): 1153-1163, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30510685

RESUMO

Both Strychnos nux-vomica Linn. (SNV) and Tripterygium wilfordii Hook F (TwHF) have received extensive attention due to their excellent clinical efficacies. However, clinical applications of SNV and TwHF have been limited by their narrow therapeutic windows and severe kidney toxicities. In this paper, based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS), endogenous metabolites after administration of SNV and TwHF extracts were detected, and biomarkers were screened successfully. Additionally, the levels of Cr and BUN in serum and pathological findings of kidneys were detected and observed. Finally, both biochemical and pathological tests of the SNV group and TwHF group indicated that kidney damage had occurred. After comparison with the normal saline group, 15 nephrotoxic biomarkers were selected from the SNV group, and 17 nephrotoxic biomarkers were selected from the TwHF group. The experimental results showed that there are some differences in the mechanisms of nephrotoxicity induced by SNV and TwHF, which are significant for revealing the mechanisms of renal injury of different medicines.

3.
Front Pharmacol ; 9: 597, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29971001

RESUMO

Current hormone-based treatments for immune thrombocytopenic purpura (ITP) are associated with potentially serious adverse reactions. Zi Dian Fang (ZDF) is a multi-target Traditional Chinese Medicine (TCM) used to treat both the symptoms and root causes of ITP, with fewer side effects than hormone-based treatments. This study analysis of the therapeutic effects of ZDF on ITP from three aspects: platelet proliferation, immunoregulation, and inflammation. After detection of 52 chemical constituents of ZDF by UPLC-Q-TOF/MS, The main targets and pathways affected by ZDF were screened by network pharmacology and verified by Western blot and ELISA. Meanwhile, metabolomics analysis were applied to a mouse model of ITP to identify and screen endogenous terminal metabolites differentially regulated by ZDF. Integrated network pharmacology and metabolomics analysis of the therapeutic effects of ZDF on ITP may be as follows: ZDF counteracts ITP symptoms mainly by inhibiting Ras/MAPKs (Ras/Mitogen-activated protein kinases) pathway, and the expression of upstream protein (Ras) and downstream protein (p-ERK, p-JNK, p-p38) were inhibited, which affects the content of effect index associated with proliferation (Thrombopoietin, TPO; Granulocyte-macrophage colony stimulating factor, GM-CSF), inflammation (Tumor necrosis factor-α, TNF-α; Interleukin-6, IL-6), immune (Interleukin-2, IL-2; Interferon-gamma, IFN-γ; Interleukin-4, IL-4), so that the body's arginine, Δ12-prostaglandin j2 (Δ12-PGJ2), 9-cis-Retinoic Acid, sphingosine-1-phosphate (S1P), oleic acid amide and other 12 endogenous metabolites significantly changes. Considering the established safety profile, the present study suggests ZDF may be a useful alternative to hormone-based therapies for the treatment of ITP.

4.
Molecules ; 22(10)2017 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-29053630

RESUMO

Schisandra chinensis (known in Chinese as WuWeiZi, WWZ) has observable effects such as astringing the lung to stop coughs, arresting sweating, preserving semen and preventing diarrhea. The major components of WWZ include lignans, triterpenoids, organic acids and fatty acids. In this paper, a reliable method for the rapid identification of multiple components in WWZ by their characteristic fragments and neutral losses using UPLC-Q-TOF/MS technology was developed. After review of the literature and some reference experiments, the fragmentation pattern of several compounds were studied and summarized. Then, according to the corresponding characteristic fragments coupled with neutral losses in the positive or negative ion mode produced by different types of substances a rapid identification of target compounds was achieved. Finally, a total of 30 constituents of WWZ were successfully identified, including 15 lignans, nine triterpenoids, three organic acids and three fatty acids. The method established in this study not only provides a comprehensive analysis of the chemical ingredients of WWZ, providing a basis for further phytochemical studies on WWZ but also provides a more efficient way to solve the problem of identification of complex chemical constituents in traditional Chinese medicines.


Assuntos
Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/química , Schisandra/química , Cromatografia Líquida de Alta Pressão/métodos , Frutas/química , Estrutura Molecular , Extratos Vegetais/análise , Extratos Vegetais/química , Espectrometria de Massas em Tandem/métodos
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