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1.
Molecules ; 27(10)2022 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-35630796

RESUMO

At present, the potential of natural products in new drug development has attracted more and more scientists' attention, and natural products have become an important source for the treatment of various diseases or important lead compounds. Geniposide, as a novel iridoid glycoside compound, is an active natural product isolated from the herb Gardenia jasminoides Ellis (GJ) for the first time; it is also the main active component of GJ. Recent studies have found that geniposide has multiple pharmacological effects and biological activities, including hepatoprotective activity, an anti-osteoporosis effect, an antitumor effect, an anti-diabetic effect, ananti-myocardial dysfunction effect, a neuroprotective effect, and other protective effects. In this study, the latest research progress of the natural product geniposide is systematically described, and the pharmacological effects, pharmacokinetics, and toxicity of geniposide are also summarized and discussed comprehensively. We also emphasize the major pathways modulated by geniposide, offering new insights into the pharmacological effects of geniposide as a promising drug candidate for multiple disorders.


Assuntos
Produtos Biológicos , Diabetes Mellitus , Gardenia , Produtos Biológicos/farmacologia , Diabetes Mellitus/tratamento farmacológico , Iridoides/farmacocinética , Iridoides/uso terapêutico
2.
Phytother Res ; 36(6): 2272-2299, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35583806

RESUMO

Iridoid glycosides (IGs) are found in many medicinal and edible plants, such as Gardenia jasminoides, Cistanche tubulosa, Eucommia ulmoides, Rehmanniae Radix, Lonicera japonica, and Cornus officinalis. Loganin, an IG, is one of the main active ingredient of Cornus officinalis Sieb. et Zucc., which approved as a medicinal and edible plant in China. Loganin has been widely concerned due to its extensive pharmacological effects, including anti-diabetic, antiinflammatory, neuroprotective, and anti-tumor activities, etc. Studies have shown that these underlying mechanisms include anti-oxidation, antiinflammation and anti-apoptosis by regulating a variety of signaling pathways, such as STAT3/NF-κB, JAK/STAT3, TLR4/NF-κB, PI3K/Akt, MCP-1/CCR2, and RAGE/Nox4/p65 NF-κB signaling pathways. In order to better understand the research status of loganin and promote its application in human health, this paper systematically summarized the phytochemistry, analysis methods, synthesis, pharmacological properties and related mechanisms, and pharmacokinetics based on the research in the past decades.


Assuntos
Cornus , Iridoides , Transdução de Sinais , Cornus/química , Humanos , Iridoides/farmacocinética , Iridoides/farmacologia , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/farmacologia
3.
J Pharm Biomed Anal ; 186: 113269, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32247162

RESUMO

This study was to develop a reliable and simple high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to detect paeoniflorin, geniposide, saikosaponin b2, liquiritin, paeonol and atractylenolide Ⅲ in beagle plasma and to study pharmacokinetic of paeoniflorin and geniposide after single-dose administration of Danzhi Xiaoyao Pill (DZXY). Chromatographic separation was performed using an Agilent C18 column, and multiple reaction monitoring (MRM) mode was used. A gradient elution procedure was used with solvent A (acetonitrile) and solvent B (0.1 % formic acid-water) as mobile phases. The elution procedure was as follows: 85 % B-30 % B (0-7 min) and 30 % B-30 % B (7.1-8 min). The flow rate was 0.3 mL/min. The column temperature was 40 ℃, and the injection volume was 10 µL. The main analytical parameters of paeoniflorin, geniposide, saikosaponin b2, liquiritin, paeonol and atractylenolide Ⅲ were m/z 525→449, m/z 433→224, m/z 780→617, m/z 417→254, m/z 167→43 and m/z 249→231, respectively. Ethyl acetate was used to extract the analytes in the plasma. Standard calibration curves of six analytes showed satisfactory linearity (r2≥0.99 2) within the determined ranges. The lower limits of quantification were 0.5 ng/mL for paeoniflorin and liquiritin, 2.5 ng/mL for geniposide and saikosaponin b2 and 1.0 ng/mL for atractylenolide Ⅲ and paeonol, respectively. The intra-day and inter-day precision (RSD %) were all below 6.94 %, and the intra-day and inter-day accuracy (RE %) were within ± 6.10 %. The recovery and ME of six analytes were 85.99 %-98.10 % and 95.78%-108.06%, respectively. Additionally, the method we established in this experiment can be successfully used to study the pharmacokinetics of paeoniflorin and geniposide in beagle plasma.


Assuntos
Medicamentos de Ervas Chinesas/análise , Glucosídeos/farmacocinética , Iridoides/farmacocinética , Monoterpenos/farmacocinética , Animais , Calibragem , Cromatografia Líquida de Alta Pressão , Cães , Glucosídeos/análise , Iridoides/análise , Limite de Detecção , Masculino , Espectrometria de Massas , Monoterpenos/análise , Controle de Qualidade , Reprodutibilidade dos Testes
4.
Biomed Chromatogr ; 34(7): e4833, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32198769

RESUMO

The identification and quantization of traditional Chinese medicine (TCM) are a challenge for researchers and industry. Using untargeted analytical methods, the in vivo detection and identification of TCM compounds are difficult because of the significant interference of endogenous substances. Fortunately, the ongoing development of new analytical technologies, especially Q-Orbitrap-MS, offers some solutions. Our team developed a holistic MS method, combining untargeted data-dependent MS2 (dd-MS2 ) modes to extensively identify TCM prototypes in vivo. The method was successfully applied to the analysis of Ligustri Lucidi Fructus (LLF). LLF is a widely used TCM with a remarkable nourishing effect on the liver and kidney. In the study, we aimed to identify the prototypes in rat plasma after oral administration of LLF extract. Following separation on an HSS T3 column, LLF extract and rat plasma were performed in untargeted dd-MS2 mode. Forty-seven compounds were characterized in rats plasma as prototypes of LLF extract. Furthermore, seven major prototypes were chosen as pharmacokinetic markers to investigate LLF's pharmacokinetic properties. The results provides comprehensive determination of compounds in LLF both in vitro and in vivo, which is important for quality control, pharmacology studies and clinical use of LLF.


Assuntos
Medicamentos de Ervas Chinesas , Glicosídeos , Iridoides , Ligustrum/química , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia de Fase Reversa , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacocinética , Frutas/química , Glicosídeos/sangue , Glicosídeos/química , Glicosídeos/farmacocinética , Iridoides/sangue , Iridoides/química , Iridoides/farmacocinética , Masculino , Medicina Tradicional Chinesa , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem/métodos
5.
Artigo em Inglês | MEDLINE | ID: mdl-32163901

RESUMO

In recent years, depression occurs frequently. Given the long duration of the disease and the high risk of recurrence, the treatment of depression requires long-term medication. Zhi-Zi-Hou-Po Decoction (ZZHPD) has been used in clinical treatment of depression and related diseases for many years, and the potential toxic damage caused by its long-term use has gradually emerged. Existing research methods that expose toxicity by a one-time administration of large doses cannot provide a reference for clinical safe drug use. In this study, the potential toxicity of ZZHPD in repeated administration was studied by urinary metabolomics with nondestructive sampling. Based on ultra-high performance liquid chromatography-quadruple-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS) and chemometrics, 33 differential biomarkers, such as 3-hydroxybutyric acid, indole sulfuric acid, hippuric acid and citric acid, were screened and dynamically tracked. The changes of some endogenous substances showed obvious time dependence. Further analysis of these time-dependent components in combination with network pharmacology revealed that the potential hepatotoxicity and nephrotoxicity of ZZHPD were related to the disorders of amino acid metabolism, energy metabolism, lipid metabolism, nucleotide metabolism and gut microflora metabolism pathway. This study can better grasp the occurrence and development of drug toxicity, and provide reference for rational and safe drug use and potential toxicity prevention of ZZHPD.


Assuntos
Antidepressivos/farmacocinética , Medicamentos de Ervas Chinesas/farmacocinética , Iridoides/farmacocinética , Animais , Antidepressivos/efeitos adversos , Antidepressivos/urina , Biomarcadores/urina , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/efeitos adversos , Iridoides/efeitos adversos , Iridoides/urina , Masculino , Metabolômica , Ratos Sprague-Dawley , Transdução de Sinais , Espectrometria de Massas em Tandem
6.
Molecules ; 25(2)2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31936853

RESUMO

Iridoids are a class of active compounds that widely exist in the plant kingdom. In recent years, with advances in phytochemical research, many compounds with novel structure and outstanding activity have been identified. Iridoid compounds have been confirmed to mainly exist as the prototype and aglycone and Ι and II metabolites, by biological transformation. These metabolites have been shown to have neuroprotective, hepatoprotective, anti-inflammatory, antitumor, hypoglycemic, and hypolipidemic activities. This review summarizes the new structures and activities of iridoids identified locally and globally, and explains their pharmacokinetics from the aspects of absorption, distribution, metabolism, and excretion according to the differences in their structures, thus providing a theoretical basis for further rational development and utilization of iridoids and their metabolites.


Assuntos
Iridoides , Modelos Biológicos , Compostos Fitoquímicos , Humanos , Iridoides/química , Iridoides/farmacocinética , Iridoides/uso terapêutico , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacocinética , Compostos Fitoquímicos/uso terapêutico
7.
Crit Rev Food Sci Nutr ; 60(15): 2532-2548, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31423808

RESUMO

Extra virgin olive oil (EVOO) polyphenols, including the secoiridoids oleocanthal (OLC) and oleacein (OLE), are attracting attention because of their beneficial effects on health. Data on OLC and OLE bioavailability are scarce, as most research on EVOO polyphenols has concentrated on hydroxytyrosol, tyrosol, and oleuropein. Consequently, relevant goals for future research are the elucidation of OLC and OLE bioavailability and finding evidence for their beneficial effects through pre-clinical and clinical studies. The aim of this review is to shed light on OLC and OLE, focusing on their precursors in the olive fruit and the impact of agronomic and processing factors on their presence in EVOO. Also discussed are their bioavailability and absorption, and finally, their bioactivity and health-promoting properties.


Assuntos
Aldeídos/farmacologia , Monoterpenos Ciclopentânicos/farmacologia , Dieta Saudável , Azeite de Oliva/química , Fenóis/farmacologia , Aldeídos/metabolismo , Aldeídos/farmacocinética , Monoterpenos Ciclopentânicos/metabolismo , Monoterpenos Ciclopentânicos/farmacocinética , Humanos , Iridoides/metabolismo , Iridoides/farmacocinética , Iridoides/farmacologia , Fenóis/metabolismo , Fenóis/farmacocinética
8.
Biomacromolecules ; 21(2): 688-700, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-31769678

RESUMO

Bioinspired nonantibiotics can prove to be a better and an efficient tool to fight against antimicrobial resistance. In our study, biomaterial composed of zinc-carboxymethyl chitosan (CMC)-genipin was investigated for this purpose. Briefly, CMC was synthesized and transformed to porous scaffolds using the freeze drying method. The scaffolds were cross-linked and stabilized with genipin and zinc (2 M zinc acetate), respectively. FTIR spectroscopic data testified Zn complex formation and pointed out the absence of water molecule like that of zinc motif containing proteins. Hence, the complex may be termed as biomimetic. Genipin (0.5%) cross-linking appeared to contribute additively to the wet compressive strength of the zinc-CMC scaffolds. Biodegradation data revealed better stability of CMC-genipin-zinc scaffolds in enzymatic and nonenzymatic conditions than their redundant controls. The scaffolds seem to support adhesion and proliferation of human dental pulp stem cells and were hemocompatible to human red blood corpuscles, as revealed by scanning electron microscopy. The scaffolds were found to be antibacterial and mildly antibiofilm when tested against biofilm-forming bacteria, that is, Staphylococcus aureus (ATCC 9144), making it a potential nonantibiotic-like biomaterial. To conclude, this organometallic complex-based biomaterial may potentially serve as a weapon against antimicrobial resistance. Furthermore, the biomaterial potentially finds its application in dental, maxillofacial, and orthopedic tissue engineering applications.


Assuntos
Adesivos/química , Materiais Biocompatíveis/farmacocinética , Materiais Biomiméticos/farmacocinética , Quitosana/análogos & derivados , Iridoides/química , Zinco/química , Adesivos/farmacocinética , Materiais Biocompatíveis/química , Materiais Biomiméticos/química , Biomimética/métodos , Células Cultivadas , Quitosana/química , Quitosana/farmacocinética , Polpa Dentária/efeitos dos fármacos , Polpa Dentária/metabolismo , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Humanos , Iridoides/farmacocinética , Teste de Materiais/métodos , Testes de Sensibilidade Microbiana/métodos , Alicerces Teciduais , Zinco/farmacocinética
9.
Food Chem ; 310: 125976, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31835230

RESUMO

Olive leaves extract (OLE) was spray-dried with maltodextrin (MD) or inulin (IN) to study the evolution of oleuropein (OE) during in vitro gastrointestinal digestion, its bioaccessibility and potential bioavailability. In the case of OLE-MD, OE was partially degraded in gastric and intestinal conditions; whereas in OLE-IN, OE was released under gastric conditions and partially degraded under intestinal conditions. In both cases, the encapsulation of OLE led to higher OE contents at the end of digestion, compared with non-encapsulated OLE, suggesting a protective role of the polysaccharides by the formation of non-covalent polysaccharides-OE complexes. OE bioaccessibility was ten times higher (p ≤ 0.05) in OLE-MD and OLE-IN than in non-encapsulated OLE. However, OE potential bioavailability, evaluated by tangential filtration, was not detected. Encapsulation technology and the encapsulant agent used may determine the release of the encapsulated compounds at a specific-site and their effect on health.


Assuntos
Produtos Biológicos/química , Inulina/química , Iridoides/farmacocinética , Polissacarídeos/química , Disponibilidade Biológica , Digestão , Inulina/metabolismo , Inulina/farmacocinética , Glucosídeos Iridoides , Iridoides/química , Folhas de Planta/química , Polissacarídeos/farmacocinética
10.
Daru ; 27(2): 695-708, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31768896

RESUMO

PURPOSE: Meningitis is an inflammation of meninges encircled the brain and spinal cord. Currently it can be treated with second generation cephalosporins which were ended up with an unresolvable problem called Multi Drug Resistance (MDR). Hence, there is a need to develop a better herbal molecule to conflict the MDR. METHODS: Hot Blanching technique followed by ultra sound assisted extraction using bio-solvent aqueous glycerol was used to extract OLE from olive leaves. QbD tool was applied to predict the interactions between Critical Material Attributes (Ratio of solid Lipid X1, Concentration of Surfactant X2) and Critical Process Parameters (Homogenization Time X3) on Critical Quality Attributes (CQA, Particle Size Y1, Zeta Potential Y2, and Entrapment Efficiency Y3). Particulate characteristics were evaluated and Invivo pharmacokinetic study was done in albino Wistar rats by IV and IN route of administration. RESULTS: Thermal studies reflect the formation of low ordered crystalline structure of lipid matrix which offers higher encapsulation of drug in NLC than physical mixture. CMA and CPP show significant effect on CQA and method operable design range was developed. Histo-pathological studies confirms that there is no signs of toxicity and in-vitro drug release studies reveals a rapid release of a drug initially followed by prolonged release of oleuropein upto 24 h. The absolute bioavailability of drug loaded NLC in brain was higher in IN route compared to NLC administered by IV route. CONCLUSIONS: In a nutshell, challenges offered by the hydrophilic OLE for brain targeting can be minimized through lipidic nature of NLC. Graphical Abstract.


Assuntos
Biologia Computacional/métodos , Iridoides/isolamento & purificação , Iridoides/farmacocinética , Nanoestruturas/química , Olea/química , Administração Intranasal , Administração Intravenosa , Animais , Disponibilidade Biológica , Química Farmacêutica , Liberação Controlada de Fármacos , Glucosídeos Iridoides , Iridoides/química , Lipídeos/química , Masculino , Tamanho da Partícula , Folhas de Planta/química , Ratos , Ratos Wistar , Tensoativos
11.
J Ethnopharmacol ; 243: 112079, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31302206

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Zhi-Zi-Hou-Po decoction (ZZHPD), a classical Chinese prescription, has been reported to improve depressive behaviors in clinic. However, definite pharmacological effects and mechanisms of ZZHPD on monoaminergic system and hippocampal neurogenesis are ambiguous. It need to be further illuminated. AIM OF THE STUDY: Our study is designed to reveal pharmacological mechanisms of ZZHPD on depression through pharmacokinetics, monoamine neurotransmitters and neurogenesis. MATERIALS AND METHODS: Chronic unpredictable mild stress (CUMS) is used to establish rats model of depression. Then, the antidepressant effects of ZZHPD are evaluated by detecting body weight, sucrose preference and forced swimming test. The regulatory functions of ZZHPD on monoaminergic system are assessed by measuring monoamine neurotransmitters, neurotransmitter precursor substances, synthesized rate-limiting enzymes and transporters. Finally, potential molecular mechanism of ZZHPD on hippocampal neurogenesis is evaluated by investigating newborn immature neuron and newborn mature neuron. RESULTS: Our results show that ZZHPD remarkably normalizes CUMS-induced decline in weight gain, decrease of sucrose consumption rate in sucrose preference test and increase of immobility time in forced swimming test. Moreover, ZZHPD significantly reverses CUMS-induced reduction of 5-hydroxytryptamine (5-HT), dopamine (DA), tryptophan (Trp), tyrosine (Tyr), tryptophan hydroxylase2 (TPH2) and tyrosine hydroxylase (TH), whereas decreases level of serotonin transporter (SERT) in CUMS-induced rats. Finally, ZZHPD obviously improves CUMS-induced decrease of newborn immature neuron and newborn mature neuron in dentate gyrus of hippocampus. CONCLUSION: This study demonstrates that ZZHPD can alleviate CUMS-induced depression-like behaviors. It is probably attributed to the fact that ZZHPD could enhance monoaminergic system and hippocampal neurogenesis. Our findings provide the new perspectives on molecular targets of ZZHPD, and it will facilitate its clinical application.


Assuntos
Antidepressivos/farmacologia , Depressão/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Iridoides/farmacologia , Estresse Psicológico/metabolismo , Animais , Antidepressivos/uso terapêutico , Monoaminas Biogênicas/metabolismo , Doença Crônica , Depressão/tratamento farmacológico , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/uso terapêutico , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Iridoides/farmacocinética , Iridoides/uso terapêutico , Masculino , Neurogênese/efeitos dos fármacos , Ratos Sprague-Dawley , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Estresse Psicológico/tratamento farmacológico , Triptofano Hidroxilase/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo
12.
Oxid Med Cell Longev ; 2019: 7480512, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31089416

RESUMO

Geniposide, an iridoid glucoside, is a major component in the fruit of Gardenia jasminoides Ellis (Gardenia fruits). Geniposide has been experimentally proved to possess multiple pharmacological actions involving antioxidative stress, anti-inflammatory, antiapoptosis, antiangiogenesis, antiendoplasmic reticulum stress (ERS), etc. In vitro and in vivo studies have further identified the value of geniposide in a spectrum of preclinical models of diabetes mellitus (DM) and cardiovascular disorders. The antioxidative property of geniposide should be attributed to the result of either the inhibition of numerous pathological processes or the activation of various proteins associated with cell survival or a combination of both. In this review, we will summarize the available knowledge on the antioxidative property and protective effects of geniposide in DM and cardiovascular disease in the literature and discuss antioxidant mechanisms as well as its potential applications in clinic.


Assuntos
Antioxidantes/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Iridoides/uso terapêutico , Modelos Moleculares , Animais , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Avaliação Pré-Clínica de Medicamentos , Humanos , Iridoides/química , Iridoides/farmacocinética , Iridoides/farmacologia
13.
Artigo em Inglês | MEDLINE | ID: mdl-31078127

RESUMO

The optimization of electrolytes, kinds and concentrations, in mobile phase for multiple constituents analyzing using high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS) was usually compromised to ensure good LC separation of partial components. However, the compromised electrolytes could lead to ionization suppression of some of the analytes. To solve the compromise of electrolytes within various components, taking phenolic acids and iridoids as a case, we used electrolyte switch in contiguous running time segments of UPLC-ESI-MS/MS to ensure chromatographic separation of chlorogenic acid, neochlorogenic acid and cryptochlorogenic acid and improve the response of geniposide. Then the method was applied for pharmacokinetic study of the four components in rat after inhaling Reduning aerosol for the first time. The complete separation of the three chlorogenic acid isomers was achieved and the LLOQs of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, and geniposide were 1, 1, 3, and 0.2 ng/mL, respectively. In conclusion, we developed a sensitive and time-saving LC-MS/MS method for the quantitative analysis of chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and geniposide in rat plasma, and this method appears to be useful for pharmacokinetic studies of Reduning aerosol. The method provided a sight to alleviate compromise of electrolytes in mobile phase for HPLC-ESI-MS in analyzing multi-components.


Assuntos
Ácido Clorogênico/sangue , Cromatografia Líquida/métodos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacocinética , Iridoides/sangue , Administração por Inalação , Aerossóis , Animais , Ácido Clorogênico/análogos & derivados , Ácido Clorogênico/química , Ácido Clorogênico/farmacocinética , Iridoides/química , Iridoides/farmacocinética , Masculino , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos
14.
Biomed Chromatogr ; 33(9): e4542, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30947404

RESUMO

A highly selective and efficient LC-MS/MS method was developed to determine the plasma concentration of magnolol, hesperidin, neohesperidin and geniposide following oral administration of Zhi-Zi-Hou-Po decoction in normal and depressed rats. Plasma samples were pretreated by protein precipitation with methanol. Chromatographic separation was performed on an XTerra® MS C18 column using a gradient elution with a mobile phase composed of acetonitrile-0.1% aqueous formic acid. The proposed method was validated to be specific, accurate and precise for the analytes determination in plasma samples. The calibration curves displayed good linearity over definite concentration ranges for the analytes. The intra- and inter-day precision of the proposed method at three different levels were all within <11.13% and the relative errors ranged from -8.46 to 8.93%. The recovery of the four compounds ranged from 82.72 to 89.08% and no apparent matrix effect was observed during sample analysis. After full validation, the established method was successfully applied for comparing the pharmacokinetics of four components between normal and depressed rats. The results showed that the AUC and Cmax of four analytes in depressed rats were significantly different from those in normal rats and might provide helpful information to guide the clinical use of Zhi-Zi-Hou-Po to treat depression.


Assuntos
Depressão , Medicamentos de Ervas Chinesas/farmacocinética , Iridoides/farmacocinética , Administração Oral , Animais , Compostos de Bifenilo/sangue , Compostos de Bifenilo/química , Compostos de Bifenilo/farmacocinética , Corticosterona/efeitos adversos , Depressão/induzido quimicamente , Depressão/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Hesperidina/sangue , Hesperidina/farmacocinética , Iridoides/administração & dosagem , Iridoides/sangue , Iridoides/química , Lignanas/sangue , Lignanas/química , Lignanas/farmacocinética , Limite de Detecção , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes
15.
Zhongguo Zhong Yao Za Zhi ; 44(2): 364-371, 2019 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-30989959

RESUMO

To investigate the " drug-guide" effect of Achyranthes bidentata saponins( ABS) and geniposide( GE) in the treatment on adjuvant arthritis( AA) rats. A UHPLC-MS/MS method for the quantitative determination of GE,zingibroside R1,ginsenoside Ro and chikusetsu saponin Ⅳa in rat blood and joint dialysate was established. After single or combined administration with ABS and GE was given to AA rat model,a microdialysis sampling method for rat joint cavity and jugular vein blood vessels was established to collect microdialysis samples. Waters Acquity HSS C_(18) column was used to separate the above four components,with mobile phase as acetonitrile-0. 1% formic acid water as mobile phase for gradient elution. ESI source was adopted for mass spectra in a negative ion scanning mode. Multiple reaction monitoring( MRM) mode was applied to detect the above four components. The methodological results showed that GE,zingibroside R1,ginsenoside Ro and chikusetsu saponin Ⅳa demonstrated a good linear relationship within the concentration ranges of 2-4 000,16-4 096,14-3 584,23-5 888 µg·L-1 respectively. The precision,accuracy,stability and matrix effect of these four ingredients reached the requirements of quantitative analysis of biological samples. The pharmacokinetic results demonstrated that the combined administration of ABS and GE( 60 mg·kg~(-1)+60 mg·kg~(-1)) can increase the degree of GE in joint cavity distribution,and the AUCjoint/AUCplasmwere twice of that of single administration of GE( 60 mg·kg~(-1)),which indicated that ABS might played a vital role in GE's distribution to joint cavity. Moreover,there was no significant difference between the distribution trend of total three ABS and GE in rats. The pharmacodynamics results showed that the combined administration of ABS and GE has stronger effects on paw swelling,arthritis index and synovial pathomorphology of AA rats than single administration of GE,which suggested that ABS might improve GE's anti-inflammatory effect in AA rats. Based on the above results,ABS has a targeting effect in increasing GE's concentration in joint cavity,with a synergy in efficacy.


Assuntos
Achyranthes/química , Artrite Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacocinética , Animais , Cromatografia Líquida de Alta Pressão , Iridoides/farmacocinética , Microdiálise , Ratos , Reprodutibilidade dos Testes , Saponinas/farmacocinética , Espectrometria de Massas em Tandem
16.
Biomed Chromatogr ; 33(7): e4526, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30834567

RESUMO

Geniposide (GE) is an iridoid glycoside compound with anti-inflammatory effect. The potential of sphingosine 1-phosphate (S1P) as a plasma marker in human diseases was suggested recently in the literature, which demonstrated that, in patients with inflammatory diseases, plasma S1P was elevated. It follows that the obstructive coronary artery disease can be predicted with serum S1P. Therefore, S1P can also be potentially used as a pharmacodynamic marker to study adjuvant arthritis (AA) rats. In the current study, a UHPLC-MS/MS method combined with the microdialysis sampling technique (using FTY720 phosphate as an internal standard) was adopted and validated to measure S1P levels in the hemodialysis fluid and joint cavity dialysates of AA rats after oral administration of GE. A S1P concentration-time curve in the dialysate was established in this study. It was demonstrated that GE exerted an anti-inflammatory effect by reducing AA-induced elevated S1P levels. It is showed that changes in S1P concentrations over time can be used to monitor the pharmacodynamic effects of GE in treating AA rats in pharmacodynamic studies.


Assuntos
Artrite Experimental/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Iridoides/farmacocinética , Lisofosfolipídeos/análise , Esfingosina/análogos & derivados , Espectrometria de Massas em Tandem/métodos , Animais , Estabilidade de Medicamentos , Iridoides/análise , Iridoides/química , Modelos Lineares , Masculino , Microdiálise , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Esfingosina/análise
17.
Molecules ; 24(3)2019 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-30708983

RESUMO

With traditional Chinese medicine (TCM) becoming widespread globally, its safety has increasingly become a concern, especially its hepatoxicity. For example, Gardenia jasminoides Ellis is a key ingredient in the Zhi-Zi-Hou-Po decoction (ZZHPD), which is a commonly-used clinically combined prescription of TCM that may induce hepatoxicity. However, the underlying toxicity mechanism of ZZHPD is not fully understood. In this study, a plasma metabolomics strategy was used to investigate the mechanism of ZZHPD-induced hepatotoxicity through profiling entire endogenous metabolites. Twenty-four Sprague-Dawley rats were randomly assigned into four groups, which were orally administered with 0.9% saline, as well as 2.7 g/kg/day, 8.1 g/kg/day, or 27 g/kg/day of ZZHPD for 30 consecutive days, respectively. Biochemical assay and metabolomics assay were used to detect serum and plasma samples, whilst histopathological assay was used for detecting liver tissues, and the geniposide distribution in tissues was simultaneously measured. The results showed that the concentration of 20 metabolites linked to amino acid, lipid, and bile acid metabolism had significant changes in the ZZHPD-treated rats. Moreover, toxic effects were aggravated with serum biochemical and histopathological examines in liver tissues as the dosage increased, which may be associated with the accumulation of geniposide in the liver as the dosage increased. Notably, our findings also demonstrated that the combined metabolomics strategy with tissue distribution had significant potential for elucidating the mechanistic complexity of the toxicity of TCM.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Medicamentos de Ervas Chinesas/efeitos adversos , Iridoides/efeitos adversos , Metaboloma , Metabolômica , Animais , Biomarcadores , Cromatografia Líquida de Alta Pressão , Biologia Computacional/métodos , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Iridoides/química , Iridoides/farmacocinética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Redes e Vias Metabólicas , Metabolômica/métodos , Ratos , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem , Distribuição Tecidual
18.
Xenobiotica ; 49(7): 762-777, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30207187

RESUMO

Zhi-Zi-Da-Huang decoction (ZZDHD) has been acknowledged with striking therapeutic effects for hepatobiliary disorders in the history of China. As decoctions are usually administrated orally, intestinal absorption, the prerequisite task of exerting therapeutic effects, is of utmost significance for screening potential active compounds and understanding the mechanism of drug action. In this work, an in vitro-in silico-in vivo strategy based on HPLC-DAD-ESI-TOF/MS was adopted for precisely profiling the intestinal absorption of ZZDHD, which integrated information obtained from rat everted gut sac model, octanol-water partition model, in silico prediction and in vivo experimental data. Besides, 34 main absorbed ingredients were selected as chemical markers to investigate the compatible interaction of the decoction on absorption level using rat everted gut sac experiment. In total, 106 compounds of ZZDHD were speculated as potential absorptive. Among them, 90 constituents predicted absorbable in at least two experimental models were finally recognized as intestinal absorbable ingredients. In addition, the absorption level of iridoids, terpenoids and flavonoid glycosides were found improved and the absorption of catechins and anthraquinones were inhibited after prescription compatibility. Taken together, this study presents a reliable strategy for evaluating intestinal absorption of herbal medicines and offers a reference for the rationality of herbal compatibility and the modernization of traditional Chinese medicine (TCM).


Assuntos
Antraquinonas , Medicamentos de Ervas Chinesas , Flavonoides , Iridoides , Animais , Antraquinonas/química , Antraquinonas/farmacocinética , Antraquinonas/farmacologia , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/química , Flavonoides/farmacocinética , Flavonoides/farmacologia , Iridoides/química , Iridoides/farmacocinética , Iridoides/farmacologia , Masculino , Ratos , Ratos Sprague-Dawley
19.
Molecules ; 23(12)2018 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-30558187

RESUMO

Qing'e Pills is a Chinese traditional herbal product, which is often used to strengthen muscles and bones in TCM (traditional Chinese Medicine) practice. Its two main component herbs, namely, Cortex Eucommiae and Fructus Psoraleae are both required to be salt-fried according to TCM theory. We have evaluated the effects of salt-frying treated herbs on Caco-2 cell uptake behavior for those active ingredients of Qing'e Pills. By investigating of various variables, including MTT, temperature, inhibitors, pH, salt concentration and herb processing methods, we tried to clarify whether the salt-processing on herbs was necessary or not. Results showed that, compared to other processing methods, the salt-frying process significantly (p < 0.01) enhanced the absorption of effective components of Qing'e Pills. The way that psoralen, isopsoralen, psoralenoside and geniposide acid entered Caco-2 cells at low concentrations was via passive diffusion. These components were not substrates of P-glycoprotein. It demonstrated that the salt-frying process not only enhanced the concentration of active components in herb extract, but also changed their absorption behaviors. Nevertheless, the mechanism of absorption behavior changing needs to be further investigated.


Assuntos
Medicamentos de Ervas Chinesas/análise , Benzofuranos/análise , Benzofuranos/farmacocinética , Células CACO-2 , Medicamentos de Ervas Chinesas/farmacocinética , Ficusina/análise , Ficusina/farmacocinética , Furocumarinas/análise , Furocumarinas/farmacocinética , Glicosídeos/análise , Glicosídeos/farmacocinética , Humanos , Iridoides/análise , Iridoides/farmacocinética , Temperatura
20.
BMC Complement Altern Med ; 18(1): 288, 2018 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-30355303

RESUMO

BACKGROUND: Iridoid glycosides (IGs), including monotropein (MON) and deacetyl asperulosidic acid (DA) as the main ingredients, are the major chemical components in Morinda officinalis How. (MO) root, possessing various pharmacological properties including anti-osteoporosis, anti-inflammation and anti-rheumatism activities.The aim of the present study was to further elucidate the pharmacological actions of MO by investigating the pharmacokinetics and tissue distribution of IGs in MO. METHODS: An ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS) method was developed and validated for simultaneous determination of MON and DA levels in plasma and various tissues of Wistar rats. MON, DA and acetaminophen (ACE) as the internal standard (IS) were extracted from rat plasma and tissue samples by direct deproteinization with methanol. The rats were administered orally at 1650 mg/kg MO and 25, 50 and 100 mg/kg MO iridoid glycosides (MOIGs) or intravenously at MOIG 25 mg/kg for pharmacokinetic study of MON and DA. In addition, 100 mg/kg MOIG was administered orally for tissue distribution study of MON and DA. Non-compartmental pharmacokinetic profiles were constructed. Tissue distributions were calculated according to the validated methods. RESULTS: Significant differences in the pharmacokinetic parameters were observed in male and female rats. The AUC0-t, Cmax and bioavailability of MON and DA in female rats were higher than those in male rats. MON and DA mainly distributed in the intestine and stomach after oral administration, and noteworthily high concentrations of MON and DA were detected in the rat hypothalamus. CONCLUSION: The results of the present study may shed new lights on the biological behavior of MOIGs in vivo, help explain their pharmacological actions, and provide experimental clues for rational clinical use of these IGs extracted from the MO root.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Glicosídeos/farmacocinética , Iridoides/farmacocinética , Morinda/química , Administração Oral , Animais , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Feminino , Glicosídeos/administração & dosagem , Glicosídeos/química , Glicosídeos Iridoides/administração & dosagem , Glicosídeos Iridoides/química , Glicosídeos Iridoides/farmacocinética , Iridoides/administração & dosagem , Iridoides/química , Masculino , Estrutura Molecular , Raízes de Plantas/química , Ratos , Ratos Wistar , Espectrometria de Massas em Tandem , Distribuição Tecidual
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