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1.
J Pharm Biomed Anal ; 169: 254-259, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-30878903

RESUMO

As one of the main constituents of Compound Danshen Dripping Pills (CDDP), Panax notoginseng (PN) plays a pivotal role in the treatment of cardiovascular diseases. Numerous researches have proved that the dammarane type saponins including notoginsenoside R1 (NR1), ginsenoside Rg1 (GRg1) and ginsenoside Rb1 (GRb1) are the main bioactive components of PN in CDDP. An efficient, realiable and sensitive liquid chromatography tandem-mass spectrometry (LC-MS/MS) analysis method for simultaneously detecting NR1, GRg1 and GRb1 in human plasma was established and applied to the pharmacokinetics study of the three PN saponins after oral administration of CDDP. The human plasma samples were processed using acetonitrile and the target materials were separated on an Eclipse plus C18 column (100 × 4.6 mm, 3.5 µm) with a gradient mobile phase consisted of water (containing 0.1% formic acid) and methanol. Within the concentration ranges of 0.25-50 ng/mL, each calibration curve exhibited an excellent linear relationship (r>0.998). The precision deviations of intra-day and inter-day analysis were lower than 9.0%, and accuracy error (RE%) ranged between 1.5% and 10.5%. The average recoveries of analytes were >64.0%. The established method was successfully applied to determine the pharmacokinetics of the three saponins in human plasma. In addition to providing guidance for clinical safe medication, the experimental results also provided a valuable and reliable basis for further pharmacological studies of PN in the human body after oral administration of CDDP.


Assuntos
Medicamentos de Ervas Chinesas/química , Plasma/química , Saponinas/sangue , Saponinas/farmacocinética , Administração Oral , Adulto , Cromatografia Líquida/métodos , Ginsenosídeos/sangue , Ginsenosídeos/química , Ginsenosídeos/farmacocinética , Humanos , Masculino , Pessoa de Meia-Idade , Panax notoginseng/química , Saponinas/química , Espectrometria de Massas em Tandem/métodos , Triterpenos/sangue , Triterpenos/química , Triterpenos/farmacocinética , Adulto Jovem
2.
Phytomedicine ; 44: 138-147, 2018 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-29544864

RESUMO

BACKGROUND: The quality of Chinese medicine (CM) has being an active and challenging research area for CM. Prof. Chang-Xiao Liu et al first proposed the concept of quality marker (Q-Marker) for the quality evaluation and control on CM. This article describe the exploratory studies of Q-Marker in salvianolic acids for injection (SAI) based on this new concept. PURPOSE: This study was designed to screen Q-Marker of SAI and establish its quality control method based on the concept of CM Q-Marker. METHODS: Based on the concept of CM Q-Marker, the SAI was investigated for the identification of chemical components and their sources. The pharmacological effects on cerebral ischemia and reperfusion induced injury in rats were also investigated. Furthermore, the target cell extracts and pharmacokinetic studies were conducted to screen Q-Markers. Finally, the fingerprints and determination based on Q-Markers were established to assess the quality of SAI more effectively. RESULTS: Overall, 20 constituents in SAI were identified. It was found that salvianolic acid B (SA-B), rosmarinic acid (RA), lithospermic acid (LA), salvianolic acid D (SA-D) and salvianolic acid Y (SA-Y) are major chemical components of SAI. Based on chemical components identifications, analysis of their sources, target cell extracts and pharmacokinetic studies, four phenolic acids, namely SA-B, RA, LA and SA-D, were screened and determined as effective Q-Markers of SAI. CONCLUSION: This study demonstrated that the described method is a powerful approach for detecting Q-Markers, which can be used as control index for the quality assessment of CM.


Assuntos
Alcenos/análise , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/normas , Polifenóis/análise , Animais , Benzofuranos/análise , Biomarcadores/análise , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Isquemia Encefálica/tratamento farmacológico , Linhagem Celular , Cinamatos/análise , Depsídeos/análise , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/farmacocinética , Endotélio Vascular/citologia , Injeções , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Masculino , Controle de Qualidade , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo
3.
Artigo em Inglês | MEDLINE | ID: mdl-29202359

RESUMO

YiQiFuMai powder injection (YQFM), derived from the classical traditional Chinese medicine (TCM) formula Shengmai San, is a modern preparation widely used to combat cardiovascular diseases, chronic heart failure (CHF) for example, in clinical practice in China. Ginsenosides are the major components of YQFM, which are responsible for its therapeutic effect. In this research, we developed a rapid, sensitive and simple method for simultaneous determination of ten ginsenosides from YQFM in CHF rat plasma with ultra-fast liquid chromatography tandem mass spectrometry (UFLC-MS/MS). After solid phase extraction (SPE), chromatography was done on an Acquity UPLC HSS T3 column (1.8µm, 100mm×2.1mm, i.d.) through an 8.0min gradient elution with acetonitrile and 0.1% formic acid in water, while mass spectrometry was performed in the positive ion electrospray ionization (ESI) mode. A good linearity was achieved for each analyte with correlation coefficient (r) >0.9920. The lower limits of quantification (LLOQ) were 1.25ng/mL for ginsenoside Rg1, Rd, Re and Rh1, 2.5ng/mL for ginsenoside Rf, Rg3, Rb2 and Rb3 and 5.0ng/mL for ginsenoside Rb1 and Rc, respectively. All the precision (RSD) data ranged from 1.7-14.5% and the accuracy (RE) data was within ±13.73%. Moreover, the validated method has been applied to investigate the integrated pharmacokinetic profiles of ginsenosides in CHF rats following intravenous administration of YQFM successfully.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/administração & dosagem , Ginsenosídeos/sangue , Ginsenosídeos/farmacocinética , Insuficiência Cardíaca/metabolismo , Espectrometria de Massas em Tandem/métodos , Animais , Doença Crônica , Medicamentos de Ervas Chinesas/farmacocinética , Modelos Lineares , Masculino , Ratos , Ratos Wistar , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
4.
J Pharm Biomed Anal ; 145: 860-864, 2017 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-28830061

RESUMO

Compound Danshen Dripping Pills (CDDP), a herbal patent medicine, is widely used in China for the prevention and treatment of cardiovascular diseases. A simple, sensitive and reliable method for simultaneous determination of danshensu (DSS), protocatechuic aldehyde (PCA), and their related metabolites, 4-hydroxy-3-methyloxyphenyl lactic acid (HMLA) and protocatechuic acid (PAA) in human plasma was developed and validated based on liquid chromatography tandem mass spectrometry (LC-MS/MS). The analytes and internal standard (IS), vanillic acid (VAA), were extracted from plasma with ethyl acetate and separated on a C18 column by using the mobile phase consisted of methanol-0.1% formic acid via gradient elution. The electrospray ionization (ESI) source was applied and operated under the multiple reaction monitoring (MRM) mode. The linear calibration curves were obtained at the concentration ranges of 0.46-1000ng/mL for DSS and PAA, and 1.38-1000ng/mL for PCA and HMLA, respectively. The inter- and intra-day precisions (RSD%) were less than 13.5%, and the accuracy (±RE%) was within 13.4%. The described method was successfully applied for the clinical pharmacokinetics of CDDP in Chinese healthy volunteers.


Assuntos
Medicamentos de Ervas Chinesas/análise , Administração Oral , Benzaldeídos , Catecóis , China , Medicamentos de Ervas Chinesas/administração & dosagem , Humanos , Hidroxibenzoatos , Lactatos , Ácido Láctico , Espectrometria de Massas em Tandem
5.
J Pharm Biomed Anal ; 140: 301-312, 2017 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-28380388

RESUMO

Jitong Ning Tablet (JTNT), a traditional Chinese herbal formula, consists of Eucommia ulmodies oliv, Angelicae pubescentis radix, Aconiti radix cocta, Corydalis yanhusuo w.t. wang, Glycyrrhizae radix et rhizoma, Paeoniae radix rubra and Radix puerariae. It has been demonstrated to show protective effects on ankylosing spondylitis and anti-inflammatory effects. The chemical compositions of JTNT, playing a key role in quality control, remain unknown. In this study, an ultra-performance liquid chromatography combined with quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS) method in both positive and negative ion mode was established to investigate the chemical constituents of JTNT formula. In total, 162 compounds including flavonoids, triterpenoids, coumarins, alkaloids, phenylpropionic acids, lignans, terpenoids, and organic acids were detected, 152 of which were unambiguously or tentatively identified by comparing their retention times and accurate mass measurement with reference compounds and data in literatures. Our results would benefit quality control and chemical basis for JTNT.


Assuntos
Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Paeonia , Comprimidos
6.
Eur J Med Chem ; 123: 577-595, 2016 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-27517806

RESUMO

Silibinin, a natural flavanone, derived from the milk thistle plant (Silybum marianum), was illustrated for several medicinal uses such as liver-protective, anti-oxidant, anti-cancer, anti-inflammation and many other. However, silibinin has poor absorbance and bioavailability due to low water solubility, thereby limiting its clinical applications and therapeutic efficiency. To overcome this problem, the combination of silibinin with phosphatidylcholine (PC) as a formulation was used to enhance the solubility and bioavailability. The results indicated that silibinin-PC taken orally markedly enhanced bioavailability and therapeutic efficiency. In addition, a deeper understanding of the signaling pathways modulated by silibinin is important to realize its potential in developing targeted therapies against liver disorders and cancer. Silibinin has been shown to inhibit many cell signaling pathways in preclinical models, demonstrating promising effects against liver disorders and cancer through in vitro and in vivo studies. This review summarizes the pharmacokinetic properties, bioavailability, safety data, clinical activities and modulatory effects of silibinin in different cell signaling pathways against liver disorders and cancer.


Assuntos
Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Transdução de Sinais/efeitos dos fármacos , Silimarina/farmacologia , Animais , Disponibilidade Biológica , Ensaios Clínicos como Assunto , Humanos , Silibina , Silimarina/farmacocinética , Silimarina/uso terapêutico
7.
J Pharm Anal ; 6(5): 318-325, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29403999

RESUMO

The herb Butea monosperma constitutes several human health beneficial components, which are mostly studied for their anticancer effects. In this study, the activity of n-butanol fractions of B. monosperma floral extract was examined on inhibiting aberrant crypt foci (ACF) formation in azoxymethane induced Wistar albino rats. The n-butanol extracts (150 mg/kg) decreased the ACF formation (per rat) by 92% and 78% in short- and long-term in vivo treatments, respectively. All the compounds in the n-butanol extract were isolated and purified using column and reverse-phase high pressure liquid chromatography (HPLC). Their structures were characterized using UV-visible spectroscopy, nuclear magnetic resonance (NMR) and electrospray-ionisation mass spectrometry (ESI-MS) to determine important flavonoids, namely isocoreopsin, butrin and isobutrin. These compounds were studied for their free radical scavenging and anticancer activities. The compound isocoreopsin showed significantly greater efficacy in cell death on human colon and liver cancer cell lines (50 µg/mL in HT-29 and 100 µg/mL in HepG2) than butrin (100 µg/mL in HT-29 and 500 µg/mL in HepG2) and isobutrin (80 µg/mL in HT-29 and 150 µg/mL in HepG2). These results suggest that isocoreopsin, butrin and isobutrin are the important key compounds for the chemoprevention of colon cancer and isocoreopsin can be considered as a promising novel drug.

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