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1.
Environ Health ; 21(1): 4, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34980104

RESUMO

BACKGROUND: The incidence rates of thyroid tumors and nodular goiter show an upward trend worldwide. There are limited reports on the risk of perchlorate and iodine on thyroid tumors, but evidence from population studies is scarce, and their impact on thyroid function is still uncertain. Therefore, the objective of this study was to investigate the association of perchlorate and iodine with the risk of nodular goiter (NG), papillary thyroid microcarcinoma (PTMC), and papillary thyroid carcinoma (PTC) and to assess the correlation between perchlorate and iodine with thyroid function indicators. METHODS: A case-control population consisting of 184 pairs of thyroid tumors and nodular goiter matched by gender and age (±2 years) was recruited in this study. Serum and urine samples were collected from each participant. Thyroid function indicators in serum were tested by automatic chemical immunofluorescence, and perchlorate and iodine levels in urine were determined by ultra-high performance liquid chromatography tandem-mass spectrometry and inductively coupled plasma-mass spectrometry, respectively. Conditional logistic regressions and multiple linear regressions were used to analyze the associations. RESULTS: Urinary perchlorate concentration was significantly higher in total cases, NG and PTC than in the corresponding controls (P < 0.05). Perchlorate was positively associated with PTC (OR = 1.058, 95% CI: 1.009, 1.110) in a non-linear dose-response relationship, but there was no association between perchlorate and NG or PTMC. Iodine was not associated with the risk of thyroid tumors and NG and did not correlate with the thyroid function indicators. Furthermore, perchlorate showed a positive correlation with thyroid stimulating hormone (TSH) at iodine adequate levels (P < 0.05), and a negative correlation with free triiodothyronine (FT3) and a positive correlation with thyroglobulin antibody (TgAb) at iodine more than adequate or excess levels (P < 0.05). CONCLUSIONS: Perchlorate can increase the risk of PTC in a non-linear dose-response relationship and disturb the thyroid hormone homeostasis and thyroid autoantibody levels.

2.
Bioresour Technol ; 343: 126062, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34601025

RESUMO

This study evaluated the performance of spent coffee biochar (SCBC)/granular activated carbon (GAC) activating peroxymonosulfate (PMS) and peroxydisulfate (PDS) for urea degradation in reclaimed water used for ultrapure water production. Results showed that catalyst and oxidant wielded a great influence on urea removal. Of them, the GAC-PMS system could completely remove urea at the least oxidant (1 g/L) and catalyst dosage (0.2 g/L). GAC activating PMS mainly depended on graphite C structure and minor oxygen functional groups. However, the amounts of urea removed by 600BC-PMS and 900BC-PMS were 57% and 70%, respectively. In the PDS system, the urea removal through GAC-PDS could reach 90%, which mainly depends on the graphite C structure of GAC. Using the same conditions, the urea removal of 900BC-PDS was similar to GAC-PDS, so it has some potential as an alternative to commercial GAC.


Assuntos
Carvão Vegetal , Poluentes Químicos da Água , Café , Peróxidos , Ureia , Água , Poluentes Químicos da Água/análise
3.
Chemosphere ; 288(Pt 1): 132459, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34619254

RESUMO

The demand for ultrapure water (UPW) in the semiconductor industry has increased in recent years, while the idea to use reclaimed water instead of tap water for UPW production has also attracted more attention. However, since urea concentration in reclaimed water is higher than that in tap water, UPW production has not been efficient. To resolve this problem, this study aims to develop a new spent coffee grounds based biochar (SCG-BC)/persulfate catalytic system as a pretreatment unit. The objective is to enhance urea removal from reclaimed water so that UPW production is more effective. In this study, the biochar used was prepared from spent coffee grounds with detailed characterization. Results strongly suggested that the urea removed by SCG-BC/persulfate catalytic system was very encouraging (up to 73%). The best possible dosages for SCG-BC and persulfate for urea removal were 0.2 and 2.0 g L-1, respectively. Furthermore, this system could remove urea effectively in a wide range of pH (3-10). Moreover, the characterizations of SCG-BC (graphite C, defective edges and functional groups, i.e. -OH, CO, carboxyl C-O) helped to activate persulfate in the catalytic process. OH• and SO4• - were all involved in this process, while the SO4• - was the main radical for urea degradation.


Assuntos
Café , Poluentes Químicos da Água , Carvão Vegetal , Ureia , Água , Poluentes Químicos da Água/análise
4.
Artigo em Inglês | MEDLINE | ID: mdl-34768050

RESUMO

As a fast, sensitive and selective method, liquid chromatography-tandem high-resolution mass spectrometry (LC-HRMS) has been used for studying the in vivo metabolism of traditional Chinese medicine (TCM). However, the rapid discovery and characterization of metabolites, especially isomers, remain challenging due to their complexity and low concentration in vivo. This study proposed a strategy to improve the structural annotation of prototypes and metabolites through characteristic ions and a quantitative structure-retention relationship (QSRR) model, and Alismatis Rhizoma (AR) triterpenes were used as an example. This strategy consists of four steps. First, based on an in-house database reported previously, prototypes and metabolites in biosamples were preliminarily identified. Second, the candidate structures of prototype compounds and metabolites were determined by characteristic ions, databases or potential metabolic pathways. Then, a QSRR model was established to predict the retention times of the proposed structure. Finally, the structures of unknown prototypes and metabolites were determined by matching experimental retention times with the predicted values. The QSRR model built by the genetic algorithm-multiple linear regression (GA-MLR) has excellent regression correlation (R2 = 0.9966). Based on this strategy, a total of 118 compounds were identified, including 47 prototypes and 71 metabolites, among which 61 unknown compounds were reasonably characterized. The typical compound identified by this strategy was successfully validated using a triterpene standard. This strategy can improve the annotation confidence of in vivo metabolites of TCM and facilitate further pharmacological research.

5.
NPJ Genom Med ; 6(1): 82, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620846

RESUMO

Despite recent advances in the prevention of cervical cancer, the disease remains a leading cause of cancer-related deaths in women worldwide. By applying the GISTIC2.0 and/or the MutSig2CV algorithms on 430 whole-exome-sequenced cervical carcinomas, we identified previously unreported significantly mutated genes (SMGs) (including MSN, GPX1, SPRED3, FAS, and KRT8), amplifications (including NFIA, GNL1, TGIF1, and WDR87) and deletions (including MIR562, PVRL1, and NTM). Subset analyses of 327 squamous cell carcinomas and 86 non-squamous cell carcinomas revealed previously unreported SMGs in BAP1 and IL28A, respectively. Distinctive copy number alterations related to tumors predominantly enriched for *CpG- and Tp*C mutations were observed. CD274, GRB2, KRAS, and EGFR were uniquely significantly amplified within the Tp*C-enriched tumors. A high frequency of aberrations within DNA damage repair and chromatin remodeling genes were detected. Facilitated by the large sample size derived from combining multiple datasets, this study reveals potential targets and prognostic markers for cervical cancer.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34509821

RESUMO

The importance to clarify the drug metabolites is beyond doubt in view of their potential efficacy and safety. However, due to the complex matrix interference, relatively low content and the co-eluting effect, it is of a great challenge to comprehensively and systematically characterize the metabolites in vivo, especially for the traditional Chinese medicines (TCMs) due to the numerous types of components. In the present study, a comprehensive off-line two-dimensional separation system combining with data independent acquisition (DIA) mode and multi-dimensional data deconvolution method was established for chromatographic separation, data acquisition and data procession of indole alkaloids in rat plasma after intragastrically administrated with the extract of Uncaria rhynchophylla at the dose of 1 g/kg. The orthogonality of the off-line 2D separation system consisting of HILIC for first-dimensional separation and the PRLC for second-dimensional separation was valuated with the "asterisk" equations, and the results showed that off-line 2D separation system had passable orthogonality (A0 = 53.3%). Furthermore, the DIA mode was applied to capture MS/MS spectra in view of its advantage in acquiring MS data, and an effective multi-dimensional deconvolution method integrating the calculation of chemical formula, the extraction of diagnostic ion, the filter of ring double bond (RDB) and the judgement of neutral loss was established to parse the spectra for the complicated DIA data for comprehensive analysis of metabolites in rat plasma. Ultimately, a total of 127 indole alkaloids were tentatively characterized, and the main metabolic pathways were inferred as demethylation, dehydrogenation, hydroxylation and deglycosylation. The off-line two-dimensional separation system was applied for the comprehensive characterization of metabolites in vivo for the first time. This study suggested a new approach to enable the enrichment, separation and analysis of the low content components in vivo.

7.
Cancers (Basel) ; 13(18)2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34572780

RESUMO

Cervical cancer tumors with undetectable HPV (HPVU) have been underappreciated in clinical decision making. In this study, two independent CC datasets were used to characterize the largest cohort of HPVU tumors to date (HPVU = 35, HPV+ = 430). Genomic and transcriptome tumor profiles and patient survival outcomes were compared between HPV+ and HPVU tumors. In vitro analyses were done to determine efficacy of the selective CDK4/6 inhibitor palbociclib on HPVU cancer cell lines. Patients with HPVU CC tumors had worse progression-free and overall survival outcomes compared to HPV+ patients. TP53, ARID1A, PTEN, ARID5B, CTNNB1, CTCF, and CCND1 were identified as significantly mutated genes (SMGs) enriched in HPVU tumors, with converging functional roles in cell cycle progression. In vitro HPVU, but not HPV+, cancer cell lines with wild type RB1 were sensitive to palbociclib monotherapy. These results indicate that HPVU status can be translated into the clinic as a predictive biomarker of poor patient response to standard of care treatments. We suggest primary cervix tumors be routinely tested for HPV prior to treatment to identify patients who will benefit from more aggressive precision-driven therapy. Our results identify palbociclib as a lead candidate as an alternative treatment strategy for HPVU CC patients.

8.
Bioorg Med Chem ; 47: 116350, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34536651

RESUMO

The antiapoptotic protein B-cell lymphoma 2 (Bcl-2), overexpressed in many tumor cells, is an attractive target for potential small molecule anticancer drug discovery. Herein, a series of novel derivatives with acyl sulfonamide skeleton was designed, synthesized, and evaluated as Bcl-2 inhibitors by means of bioisosteric replacement. Among them, compound 24g demonstrated equal efficient inhibition activity against RS4;11 cell line compared to positive control ABT-199. Moreover, it showed improved selectivity for Bcl-2/Bcl-xL inhibitory effects, the result of which was consistent with platelet toxicity studies. In vitro and in vivo pharmacokinetic properties of compound 24g had a significantly improved profiles. Taken together, those results suggested it as a promising candidate for development of novel therapeutics targeting Bcl-2 in cancer.

9.
Cancer Manag Res ; 13: 5775-5784, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34321924

RESUMO

Purpose: Human polycomb protein 2(hPC2) is a vital component of polycomb repressive complex 1(PRC1). It plays a critical role in tumorigenesis and progression. However, whether HPC2 expression affects the prognosis of patients with nasopharyngeal carcinoma (NPC) is currently unclear. In the present study, we investigated the expression of hPC2and elucidated its clinical prognostic significance in NPC. Patients and Methods: The expression of hPC2 in 180 NPCs samples was examined by immunohistochemistry (IHC) and evaluated by H-score staining intensity. Receiver operator characteristic (ROC) curve analysis was performed to determine cut-off values of hPC2 expression. The chi-square test, Kaplan-Meier (Log rank test), and the Cox proportional hazards model were utilized to analyze the data. Results: We found hPC2 is highly expressed in 48.3% of NPC specimens, which significantly correlated with T stage (p=0.032), N stage (p=0.006), and clinical stage (p=0.003). Kaplan-Meier analysis indicated that NPCs with high hPC2 expression tended to have a lower cumulative rates of overall survival (OS, p<0.001), recurrence-free survival (RFS, p=0.001), and distant metastasis-free survival (DMFS, p=0.003). In the NPCs subgroup, T3-T4, N2-N3, and stages III-IV, high hPC2 expression also had a prognostic impact on worse outcome in terms of OS, RFS, and DMFS. More importantly, multivariate analyses demonstrated that hPC2 expression was an independent prognostic factor for OS (hazard ratio [HR], 95% (confidence interval [CI]), p=0.001), RFS (HR, 95% CI, p=0.018), and DMFS (HR, 95% CI, p=0.022). Conclusion: We present evidence that high expression of hPC2 correlated with poorer prognosis in NPC. hPC2 could serve as a novel prognostic biomarker and might be a promising therapeutic target for NPC.

10.
Chin J Nat Med ; 19(6): 473-480, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34092298

RESUMO

Huashi Baidu prescription (HSBDF), recommended in the Guideline for the Diagnosis and Treatment of Novel Coronavirus (2019-nCoV) Pneumonia (On Trials, the Seventh Edition), was clinically used to treat severe corona virus disease 2019 (COVID-19) with cough, blood-stained sputum, inhibited defecation, red tongue etc. symptoms. This study was aimed to elucidate and profile the knowledge on its chemical constituents and the potential anti-inflammatory effect in vitro. In the study, the chemical constituents in extract of HSBDF were characterized by UPLC-Q-TOF/MS in both negative and positive modes, and the pro-inflammatory cytokines were measured by enzyme-linked immunosorbent assays (ELISA) to determine the effects of HSBDF in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The results showed that a total of 217 chemical constituents were tentativedly characterized in HSBDF. Moreover, HSBDF could alleviate the expression levels of IL-6 and TNF-α in the cell models, indicating that the antiviral effects of HSBDF might be associated with regulation of the inflammatory cytokines production in RAW264.7 cells. We hope that the results could be served as the basic data for further study of HSBDF on anti-COVID-19 effect.


Assuntos
Anti-Inflamatórios/química , Antivirais/química , COVID-19/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Extratos Vegetais/química , SARS-CoV-2/efeitos dos fármacos , Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Humanos , Extratos Vegetais/uso terapêutico
11.
Environ Int ; 155: 106665, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34098336

RESUMO

Dioxins, environmentally stable and ubiquitous, have been found to induce metabolic changes especially in lipids and be related to multiple diseases. However, limited study is available on lipid alternations related to human exposure to dioxins. This study aims to explore the serum lipidomic characterization and to understand the underlying mechanisms of adverse health risks associated with dioxin exposure. A lipidomic study integrating nontargeted lipidomics, and targeted free fatty acid (FFA) and acyl-coenzyme A (acyl-CoA) analyses were conducted to investigate the 94 serum samples from two groups of male workers with remarkably different dioxin concentrations. The obtained results exhibited distinct lipidomic signatures between the high and low exposed groups. A total of 37 lipids were identified with the significant changes. The results revealed that dioxin exposure caused accumulations of triglyceride (TG), ceramide (Cer) and sphingoid (So), remodeling of glycerophospholipid (GP), imbalanced FFA metabolism, as well as upregulation of platelet-activating factor (PAF). These findings implied the associations between dioxin exposure and potential adverse health risks including inflammation, apoptosis, cardiovascular diseases (CVDs), and liver diseases. This study is the first to explain the associations between dioxin exposure and health effects at the level of lipid metabolism.


Assuntos
Dioxinas , Transtornos do Metabolismo dos Lipídeos , China , Dioxinas/toxicidade , Humanos , Metabolismo dos Lipídeos , Lipidômica , Masculino
12.
Int J Chron Obstruct Pulmon Dis ; 16: 1425-1435, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34079246

RESUMO

Background: Chronic obstructive pulmonary disease (COPD) is often combined with type 2 diabetes mellitus (T2DM) in clinical, and with poor prognosis. In recent years, research shows that inflammation is a common characteristic of COPD and T2DM. T-helper 17 cell (Th17)/regulatory T-cell (Treg) balance controls inflammation and may be important in the pathogenesis of COPD combined with T2DM patients. This study investigated the characteristics of Th17, Treg and related inflammatory factors in COPD combined with T2DM patients and the potential mechanism. Methods: Application of flow cytometry technology, real-time fluorescent quantitative PCR and ELISA to detect the changes in peripheral blood of Th17 and Treg number and the expression of key transcription factors and related cytokines in COPD combined T2DM patients were performed. Results: Patients with COPD combined with T2DM revealed significant increase in peripheral Th17, Th17 related cytokines (IL-17A, IL-17F, IL-21, IL-23, IL-6) and transcription factor (RORγt) levels and significant decrease in Treg, Treg-related cytokines (IL-10, TGFß1) and transcription factor (Foxp3) as compared with patients with COPD, T2DM and healthy controls. Conclusion: Th17/Treg functional imbalance exists in patients with COPD combined with T2DM, indicating a potential role of Th17/Treg imbalance in the formation and progression of COPD combined with T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Doença Pulmonar Obstrutiva Crônica , Citocinas , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Humanos , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Linfócitos T Reguladores , Células Th17
13.
Sci Total Environ ; 785: 147254, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33933770

RESUMO

The recent and vigorous developments in semiconductor technology strictly request better quality and large quantity of ultrapure water (UPW) for their production. It is crucial to secure a large amount of raw water for the future development of UPW production. Using reclaimed water as alternative raw water source to produce UPW is therefore considered the feasible trend and solution for sustainable use of water resources towards a common future practice in UPW production. The challenge of using reclaimed water is due to its higher content of organic pollutants, especially small molecule organic pollutants such as urea, which are difficult to remove through traditional UPW production process. Consequently, improving the existing UPW production process to meet the water standard desired in the semiconductor industry is essential. This paper reviewed the current traditional processes for removing organic matters in UPW production, including ion-exchange (IX) adsorption, granular activated carbon (GAC) adsorption, reverse osmosis (RO) and ultraviolet (UV) irradiation. The potential problems in the actual UPW production process were identified when using reclaimed water as raw water source. A new strategy of applying the advanced oxidation process (AOPs) to UPW production as a supplementary unit to guarantee UPW quality was proposed. Its feasibility and research focus were then analyzed and discussed in obtaining a new solution for a future development of the UPW production process.

14.
J Sep Sci ; 44(14): 2717-2727, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33963673

RESUMO

Comprehensive characterization of traditional Chinese medicine prescriptions has long been a hurdle due to the chemical complexity and the lack of analytical tools. Mahuang decoction is a well-known traditional Chinese medicine prescription widely used for sweating and relieving the exterior, relieving cough and asthma, but it was insufficiently chemically scrutinized. In this study, the chemical component information of Mahuang decoction was investigated by ultrahigh-performance liquid chromatography tandem linear ion trap-Orbitrap mass spectrometry. A new data processing tool, feature-based molecular networking, was introduced for grouping and elucidating the compounds. In this way, 156 chemical components were identified or tentatively characterized, including alkaloids, triterpenoid saponins, flavanone-O-glycosides, flavone-C-glycosides, and procyanidins. Thus, this research provides a solid foundation for further development of Mahuang decoction, and the adopted method is expected to be applied to other traditional Chinese medicine prescriptions.

15.
J Sep Sci ; 44(12): 2427-2437, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33885223

RESUMO

Authentication of Chinese medicine materials in prescriptions is extremely difficult due to the complicated chemical matrix. A strategy integrating in-depth profiling, chemical marker selection, and selected detection was established and exemplarily applied to authenticate paeony root in ShaoYao-GanCao decoction. First, an ultra-performance liquid chromatography/linear trap quadrupole-Orbitrap method was developed to probe the chemical compositions of the decoction. Second, 20 batches of decoctions prepared from white paeony root and red paeony root were compared by a metabolomics method, and multistep chemometrics analysis distinguished the chemical markers. Third, an ultra-performance liquid chromatography/QDa-selected ion monitoring method was developed to authenticate the paeony root in decoctions. As a result, 161 compounds were characterized, including 84 triterpene saponins, 42 flavonoids, and 10 monoterpenes. Four chemical markers and paeoniflorin were successfully screened out as chemical markers for white paeony root. The selected ion monitoring method easily differentiated authentic decoction (prepared from white paeony root) from fraud decoction (prepared from red paeony root) by monitoring the above five chemical markers. In conclusion, the strategy was proved effective in authentication of paeony root in ShaoYao-GanCao decoction, and it can also be applied to authenticate other Chinese medicine materials in prescriptions, which will greatly avail the quality enhancement of prescriptions.

16.
Chin J Nat Med ; 19(4): 295-304, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33875169

RESUMO

In this study, a high performance thin-layer chromatography/single quadrupole mass spectrometry QDa (HPTLC-QDa) method for robust authentication of Ganoderma lucidum, a popular and valuable herbal medicine, has been developed. This method is simple and practical, which allows direct generation of characteristic mass spectra from the HPTLC plates automatically with the application of in situ solvent desorption interface. The HPTLC silica gel plates were developed with toluene-ethyl formate-formic acid (5 : 5 : 0.2, V/V) and all bands were transferred to QDa system directly in situ using 80% methanol with 0.1% formic acid as desorption solvent. The acquired HPTLC-QDa spectra showed that luminous yellow band b3, containing ganoderic acid B/G/H and ganodeneric acid B, the major active components of Ganoderma, could be found only in G. lucidum and G. lucidum (Antler-shaped), but not in G. sinense and G. applanatum. Moreover, bands b13 and b14 with m/z 475/477 and m/z 475/491/495, respectively, could be detected in G. lucidum (Antler-shaped), but not in G. lucidum, thus allowing simple and robust authentication of G. lucidum with confused species. This method is proved to be simple, practical and reproducible, which can be extended to analyze other herbal medicines.


Assuntos
Ganoderma , Cromatografia em Camada Delgada , Ganoderma/química , Ganoderma/classificação , Espectrometria de Massas , Análise Espectral
17.
J Agric Food Chem ; 69(16): 4849-4857, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33849274

RESUMO

Due to the high price and limited supply of Panax notoginseng, a large number of samples adulterated with the leaves appear in the market. A group of new malonyl ginsenosides were exclusively detected in the P. notoginseng leaves (PNL). Targeted isolation of the malonyl ginsenosides was guided by UPLC-QDa MS. HRMS, 1D/2D NMR, and chemical methods were used for structural identification. A selected ion monitoring method was developed based on UPLC-QDa MS to detect the adulterations. In addition, the anti-inflammatory activities and the collision-induced dissociation features of the isolated saponins were studied. As a result, eight new 3-OH malonylated dammarane-type triterpene oligoglycosides (notoginsenosides L3-L10) were obtained from PNL. Adulteration with PNL can be easily detected with limit of detection as low as 0.06%. To sum up, the isolated ginsenosides can be used as quality markers for fraud detection, which will promote the quality control of the notoginseng products.


Assuntos
Ginsenosídeos , Panax notoginseng , Panax , Saponinas , Espectroscopia de Ressonância Magnética , Folhas de Planta
18.
Fitoterapia ; 152: 104858, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33677011

RESUMO

Traditional Chinese medicines (TCMs), have been widely used for the prevention, treatment, and cure of various diseases for thousands of years in China and Asian countries. It is usually applied either alone or in combination with synthetic drugs or other herbs to be more effective. However, the evaluation of TCMs against the main phase I metabolic enzyme CYP3A4 in vitro was limited. In the present study, a high throughput method based on an isoform-specific probe was applied to evaluate the inhibitory effect of 225 frequently-used TCMs on CYP3A4 activity. The results showed that 25 TCM herbs possessed inhibition effect with residual activity below 50%, and four TCMs (Curcumae Rhizoma, Piperis Longi Fructus, Dalbergiae Odoriferae Lignum, Arisaematis Rhizoma Preparatum) had fairly strong inhibition effect with residual activity below 20%. In an attempt to validate the results obtained from isoform-specific probe, the Curcumae Rhizoma with lowest residual activity was further tested to screen main bioactive constituents which possessed significant inhibitive effect. The crude extract of Curcumae Rhizoma was fractionated to investigate the inhibition effect of each fraction, the results showed that fractions 9-13 exhibited obvious inhibitory effect, and the main constituent (curdione) was identified with standard reference. The molecular docking results verified that the inhibiting effect of curdione could be explained that curdione was interacted with 7 amino acid residues to generate the hydrophobic interaction, and also interacted with imidazole to form hydrogen bond. It is anticipated that the results could be used as reference data to avoid drug-drug interaction and guide the clinical application of TCM or prescriptions.


Assuntos
Inibidores do Citocromo P-450 CYP3A/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Curcuma/química , Citocromo P-450 CYP3A , Humanos , Medicina Tradicional Chinesa , Microssomos Hepáticos/efeitos dos fármacos , Simulação de Acoplamento Molecular , Rizoma/química
19.
J Chromatogr A ; 1643: 462029, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33752090

RESUMO

The inherent complexity of traditional Chinese medicines necessitates the application of multi-dimensional information to accomplish comprehensive profiling and confirmative identification of their chemical components. In this study, we display an enhanced strategy by integrating offline superimposed two-dimensional separation (S-2D-LC) with mass defect filter and diagnostic ion filter to comprehensively characterize the alkaloid composition of Fritillariae Pallidiflorae Bulbus (FPB). The superimposed HILIC × RP and UPCC × RP offline two-dimensional liquid chromatography system was constructed with superior orthogonality (R2=0.004 and R2=0.001) for chromatographic separation. In total, 70 fractions were collected after the first-dimensional chromatographic separation (HILIC and UPCC) and then analyzed by the second-dimensional reversed phase (RP) liquid chromatography coupled with Q-TOF/MS/MS in FAST DDA acquisition mode. A four-step interpretation strategy combining mass defect filter with diagnostic ion filter was developed to rapidly characterize alkaloids in Fritillaria species. Ultimately, a sum of 529 Fritillaria alkaloids were characterized from two botanical origins of FPB. The integrated strategy is practical to efficiently expose and comprehensively characterize more trace and isomeric components in complex herbal medicines.


Assuntos
Alcaloides/análise , Fritillaria/química , Esteroides/análise , Cromatografia de Fase Reversa , Medicamentos de Ervas Chinesas/química , Interações Hidrofóbicas e Hidrofílicas , Peso Molecular , Espectrometria de Massas em Tandem
20.
J Pharm Biomed Anal ; 198: 113999, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33706145

RESUMO

Ginsenoside Rg1 (Rg1) was one of the dominent active components in several Panax medicinal species as Panax notoginseng and Panaxginseng with diversified bioactivities. However, the study on tissue distribution of Rg1 remained limited and needed to be further explored for elucidation of its spatial distribution. In the present study, a LC-MS/MS combined with nanospray desorption electrospray ionization (DESI) mass spectrometry method was developed for exploration of tissue distribution of Rg1 at different time points after intravenous administration to rats. Furthermore, a MS inlet-heat method was developed to improve the imaging efficacy of Rg1 in brain tissue. The results obtained from LC-MS/MS analysis indicated that kidney possessed the highest tissue concentration, followed by liver, lung, spleen, heart and brain. Meanwhile, the elimination of Rg1 was swift within 1 h. For the spatial distribution of Rg1 by DESI-MS, Rg1 mainly accumulated in the pelvis section of kidney. Meanwhile, the imaging result of brain implied that Rg1 might be distributed in the pons and medulla oblongata region of brain at 15 min after intravenous administration. It is anticipated that the data on tissue distribution of Rg1 could provide references for further probing its efficacy and drug development.


Assuntos
Ginsenosídeos , Espectrometria de Massas por Ionização por Electrospray , Animais , Cromatografia Líquida , Ratos , Espectrometria de Massas em Tandem , Distribuição Tecidual
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