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1.
J Am Chem Soc ; 146(4): 2798-2804, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38145451

RESUMO

The combination of the chiral concept and inorganic nanostructures holds great potential for significantly impacting catalytic processes and products. However, the synthesis of inorganic nanomaterials with engineered chiroptical activity and identical structure and size presents a substantial challenge, impeding exploration of the relationship between chirality (optical activity) and catalytic efficiency. Here, we present a facile wet-chemical synthesis for achieving intrinsic and tunable chiroptical activity within colloidal copper oxide nanostructures. These nanostructures exhibit strong spin-polarization selectivity compared with their achiral counterparts. More importantly, the ability to engineer chiroptical activity within the same type of chiral nanostructures allows for the manipulation of spin-dependent catalysis, facilitating a study of the connection between the chiroptical magnitude (asymmetric factor) and catalytic performance in inorganic nanostructures. Specifically, using these materials as model catalysts in a proof-of-concept catalytic reaction, we reveal a linear correlation between the asymmetric factor of chiral nanomaterials and the efficiency of the catalytic reaction. This work paves the way for the development of chiral inorganic nanosystems and their application in catalysis through chiroptical engineering.

2.
PLoS One ; 18(8): e0289121, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37556490

RESUMO

Radix Scutellaria-Licorice drug pair (RSLDP), a frequently used herbal pair with the effect of clearing heat and detoxifying, is the commonly employed drug pair in TCM prescriptions for the treatment of COVID-19. Until now, the metabolism feature and anti-COVID-19 mechanism of RSLDP have not been fully elucidated. In this study, a sensitive and rapid method was developed for the separation and identification of the absorbed constituents of RSLDP in the rat plasma by UHPLC-QTOF-MS. Additionally, we optimized the conventional methodologies of network pharmacology and proposed a new concept called target network pharmacology (T-NP). It used the absorbed constituents and the corresponding targets to generate a compound-target network, and compared to conventional network pharmacology, it could reduce false-positive results. A total of 85 absorbed constituents were identified or tentatively characterized in dosed plasma, including 32 components in the group of Radix Scutellaria, 27 components in the group of Licorice, and 65 components in the group of RSLDP. The results showed that the compatibility of Radix Scutellaria and Licorice increased the number of components in vivo. We found that 106 potential targets among the 61 active compounds in RSLDP were related to COVID-19. And 12 targets (STAT3, AKT1, EGFR, HSP9AA1, MAPK3, JUN, IL6, VEGFA, TNF, IL2, RELA, and STAT1) could be core targets for RSLDP in treating COVID-19. Results from these targets indicate that RSLDP treatment of COVID-19 mainly involves response to chemical stress, response to oxygenates, positive regulation of cytokines, PI3K-Akt signaling pathway, AGE-RAGE signaling pathway for diabetic complications, virus-related pathways such as novel coronavirus and human cytomegalovirus infection, inflammatory immune-related pathways, and so on. The metabolism feature of RSLDP in vivo was systematically uncovered. The combined use of the T-NP method could discover potential drug targets and disclose the biological processes of RSLDP, which will clarify the potential mechanisms of RSLDP in the treatment of COVID-19.


Assuntos
COVID-19 , Medicamentos de Ervas Chinesas , Glycyrrhiza , Scutellaria , Ratos , Humanos , Animais , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Cromatografia Líquida de Alta Pressão , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Simulação de Acoplamento Molecular
3.
PLoS One ; 18(8): e0289656, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37535556

RESUMO

The objection of this study was to investigate the effects of vindoline(VDL) on the cytochrome P450 (CYP 450) isoforms (CYP1A2, 2B, 2C11, 2D1 and 3A) in rats. Firstly, the rats were randomly divided into VDL pretreatment group and blank group, each group had six rats. VDL pretreatment group was administrated VDL (20 mg·kg-1) by oral gavage for fifteen days consecutively, and the equivalent CMC-Na solution without VDL was given to the blank group by gavage. Secondly, a cocktail of caffeine, bupropion, diclofenac, dextromethorphan and midazolam was then administered on the sixteenth day. Finally, blood samples were collected at the specified time point, and the plasma concentration of the probe drug was determined by UHPLC-QTOF-MS/MS. The effects of VDL on the activity of these CYP enzymes in rats were evaluated by pharmacokinetic parameters. VDL pretreatment group compared with the blank group, accelerated the metabolism of diclofenac, and weakened the metabolism of caffeine. These results suggested that VDL could induce the activity of CYP2C11, and inhibits the activity of CYP1A2, but had no significant effects on CYP2B, CYP2D1 and CYP3A. The results in this study can provide beneficial information for the later clinical application of VDL.


Assuntos
Catharanthus , Citocromo P-450 CYP1A2 , Ratos , Animais , Citocromo P-450 CYP1A2/metabolismo , Catharanthus/metabolismo , Cafeína/farmacologia , Espectrometria de Massas em Tandem , Diclofenaco/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Citocromo P-450 CYP3A/metabolismo
4.
iScience ; 26(7): 107022, 2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37360683

RESUMO

Intracerebral hemorrhage usually manifests as strong neuroinflammation and neurological deficits. There is an urgent need to explore effective methods for the treatment of intracerebral hemorrhage. The therapeutic effect and the possible mechanism of induced neural stem cell transplantation in an intracerebral hemorrhage rat model are still unclear. Our results showed that transplantation of induced neural stem cells could improve neurological deficits by inhibiting inflammation in an intracerebral hemorrhage rat model. Additionally, induced neural stem cell treatment could effectively suppress microglial pyroptosis, which might occur through inhibiting the NF-κB signaling pathway. Induced neural stem cells could also regulate the polarization of microglia and promote the transition of microglia from pro-inflammatory phenotypes to anti-inflammatory phenotypes to exert their anti-inflammatory effects. Overall, induced neural stem cells may be a promising tool for the treatment of intracerebral hemorrhage and other neuroinflammatory diseases.

5.
Nano Lett ; 23(10): 4384-4389, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37162145

RESUMO

Circularly polarized luminescence (CPL) is well-studied in molecular systems but has been rarely reported in pure inorganic nanoscale crystals. Herein, we develop a family of pure inorganic rare-earth nanowires with robust and color-tunable CPL emissions. The chiral rare earth nanowires possess intrinsic atomic chirality with controlled handedness that is guided by the enantiomers with molecular chirality in the synthesis. By varying luminescent ions incorporated in the crystal lattice, color-tunable CPL can be achieved and is thermally robust, preserving emission over 300 °C, distinct from existing CPL-active materials. Moreover, as a proof of concept, we demonstrate that the synthesized nanostructures can be easily dispersed in a polymer matrix to enable transparent and flexible CPL films. This study opens up a promising avenue to design robust and tunable CPL materials helpful to the understanding of inorganic chiral information and capable of further applications in novel optoelectronic devices.

6.
Biomed Chromatogr ; 37(9): e5682, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37158044

RESUMO

Isodon excisoides (Y.Z.Sun ex C.H.Hu) H. Hara has been often used to treat liver diseases in folk medicine. However, the potential hepatoprotective mechanism of I. excisoides remains unclear. In this study, the mechanism of I. excisoides in alleviating drug-induced liver injury (DILI) was explored using a strategy combining metabolomics with network pharmacology for the first time. First, serum metabolomics was applied to identify differential metabolites and enrich metabolic pathways. The potential targets of I. excisoides for the treatment of DILI were investigated by network pharmacology. Subsequently, a comprehensive network of network pharmacology and metabolomics was established to find the key genes. Finally, molecular docking technology was used to further verify the key targets. As a result, four key genes including TYMS, IMPDH2, DHODH, and ASAH1 were identified. The proteins produced by these genes had high affinity with the corresponding diterpenoids. These results indicate that the components of I. excisoides play a liver-protective role by affecting the aforesaid key genes and key proteins. Our results offer a novel strategy for determining the pharmacological effects and potential targets of natural compounds.

7.
Artigo em Inglês | MEDLINE | ID: mdl-37059010

RESUMO

Hangju (HJ), the dried flower heads of Chrysanthemum morifolium Ramat., has a significant hepatoprotective effect. However, its underlying protection mechanism against acute liver injury (ALI) has been unclear. An integrated strategy based on metabolomics with network analysis and network pharmacology was developed to explore the potential molecular mechanism of HJ on ALI protection. Firstly, differential endogenous metabolites were screened and identified by metabolomics approach and metabolic pathway analysis was performed by MetaboAnalyst. Secondly, marker metabolites were used to construct metabolite-response-enzyme-gene networks and discover hub metabolites and potential gene targets in network analysis. Thirdly, hub genes through the protein-protein interaction (PPI) network were acquired by the aid of network pharmacology. Finally, the gene targets were taken to intersect with the relevant active ingredients for validation by molecular docking. In total, 48 flavonoids were identified in HJ, which were associated with 8 potential therapeutic targets in network pharmacological analysis. Biochemistry and histopathology analysis demonstrated that HJ exerted hepatoprotective effects. 28 biomarkers were successfully identified as possible biomarkers for the prevention of ALI. The sphingolipid metabolic pathway and the glycerophospholipid metabolic pathway was considered a crucial signaling pathway by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In addition, phosphatidylcholine and sphingomyelin were considered as hub metabolites. Twelve enzymes and 38 genes were considered as potential targets in the network analysis. Based on the combined analysis above, HJ was shown to modulate 2 key upstream targets, including PLA2G2A and PLA2G4A. Molecular docking showed that active compounds of HJ had high binding affinity with these key targets. In conclusion, the flavonoid components of HJ can inhibit PLA2 and regulate glycerophospholipid and sphingolipid metabolism pathway to delay the pathological process of ALI, which may be a potential mechanism of HJ against ALI.


Assuntos
Chrysanthemum , Medicamentos de Ervas Chinesas , Farmacologia em Rede , Simulação de Acoplamento Molecular , Metabolômica , Flavonoides , Glicerofosfolipídeos
8.
J Pharm Pharmacol ; 75(4): 559-573, 2023 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-36821628

RESUMO

OBJECTIVES: Corni Fructus is one of the most famous traditional Chinese medicines (TCMs) for the treatment of various chronic kidney diseases. Wine-processed Corni Fructus (WCF) is the main processed form of Crude Corni Fructus (CCF). In this study, potential mechanisms of action of CCF and WCF on chronic renal failure (CRF) model were developed to explore wine-processed mechanism of Corni Fructus. METHODS: An integrated strategy combining metabolomics, network analysis and bioinformatics analysis has been established to investigate the therapeutic mechanisms of WCF and CCF in rats with CRF. KEY FINDINGS: The histopathological results showed that both WCF and CCF improved kidney injury and dysfunction of CRF rats, but WCF was more effective than CCF. Metabolic pathway analysis indicated that 24 metabolites and 5 major disturbed pathways associated with CCF, while WCF regulated 27 metabolites and 2 metabolic pathways. Bioinformatic analysis and network analysis revealed that 8 genes and 7 genes were regulated by CCF and WCF on CRF rats, respectively. The quantitative real-time polymerase chain reaction experiments verified the regulatory ability of CCF and WCF on the expression of 4 genes. CONCLUSIONS: An integrated strategy combined metabolomics, network analysis and bioinformatics was established to provide valuable holistic insight to explore the processing mechanism of TCMs.


Assuntos
Cornus , Medicamentos de Ervas Chinesas , Falência Renal Crônica , Insuficiência Renal Crônica , Vinho , Ratos , Animais , Falência Renal Crônica/tratamento farmacológico , Metabolômica , Medicamentos de Ervas Chinesas/farmacologia
9.
Rapid Commun Mass Spectrom ; 37(7): e9473, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36645740

RESUMO

RATIONALE: Anemarrhenae Rhizoma (AR) has been an often used traditional Chinese medicine (TCM) for a long time. Its salt-processed form is one of the most common application forms. Modern pharmacological research has shown that the salt-processed product has various significantly enhanced pharmacological activities. However, the pharmacodynamic material basis of this change is not yet known. The aim of this study was to develop a strategy to screen pharmacodynamic substances in AR and salt-processed AR (SAR). METHODS: An integrated strategy combining plant metabolomics with molecular docking technology was established to screen pharmacodynamic substances. The plant metabolomics analysis was performed to select the chemical markers between AR and SAR. Then, molecular docking technology was applied to explore the relationship between chemical markers and diabetes targets (α-glucosidase). Finally, potential quality control markers were screened. RESULTS: There were significant differences in the quantification of nine steroidal saponins between AR and SAR. The results of plant metabolomics analysis showed a quite clear discrimination including 29 chemical markers between AR and SAR. Taking the hypoglycemic activity into consideration, 16 steroidal saponins were selected as potential quality markers. CONCLUSIONS: The developed method not only supplied an optional solution to search for pharmacophores in AR and SAR, but also provided a foundation for the study of the differential components and pharmacodynamics in various processed products of TCMs.


Assuntos
Anemarrhena , Medicamentos de Ervas Chinesas , Saponinas , Medicamentos de Ervas Chinesas/química , Simulação de Acoplamento Molecular , Anemarrhena/química , Controle de Qualidade , Saponinas/análise , Metabolômica
10.
Rapid Commun Mass Spectrom ; 37(1): e9403, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36184262

RESUMO

RATIONALE: Fritillaria cirrhosae bulbus (BFC), a typical traditional Chinese medicine with multiple botanical sources, has been used for relieving cough and reducing sputum. Studies have shown that there were obvious differences in the chemical compositions and clinical efficacy of different sources of BFC. How to characterise BFC from botanical sources accurately and quickly is vital for drug quality evaluation and clinical applications. METHODS: In the present study, an integrated strategy of plant metabolomics combined with the target network pharmacology was developed to characterise BFC. Plant metabolomics analysis was performed to screen out the chemical markers of six species of BFC. Then, target network pharmacology was applied to explore the relationship between chemical markers and related diseases. Finally, potential Q-markers for species characterization were selected by combined analysis of plant metabolomics and the target network pharmacology. RESULTS: A total of 67 Fritillaria alkaloid compounds were identified. Six species showed clear characterization by multivariate statistical analysis, resulting in 12 chemical markers. Meanwhile, a total of nine components related to asthma were screened out based on the target network pharmacology. Taking content difference and pharmacological activity into consideration, nine constituents were selected as potential Q-markers. CONCLUSION: The method developed provided not only a standard protocol for characterising different species of BFC directly, but also an effective approach for multisource medicines discrimination.


Assuntos
Medicamentos de Ervas Chinesas , Fritillaria , Medicamentos de Ervas Chinesas/química , Farmacologia em Rede , Fritillaria/química , Medicina Tradicional Chinesa , Metabolômica
11.
RSC Adv ; 12(54): 34971-34989, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36540235

RESUMO

Taiju and Duoju are products of Hangbaiju (HJ) obtained during different collection periods, and they have been commonly used as ingredients in tea beverages and dietary traditional Chinese medicine. This study reports an integrated strategy based on metabolomics, bioinformatics and molecular docking to further explore the effect of the harvesting period on the metabolic profile and clinical efficacy of HJ. Firstly, gas chromatography-mass spectrometry (GC-MS) and ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) were employed for non-targeted metabolomics profiling of essential oils and flavonoids. A sequential window acquisition of all theoretical fragment-ion spectra information-dependent acquisition (SWATH-IDA) bi-directionally verified (SIBDV) method was developed that integrates the advantages of both SWATH and IDA in characterizing flavonoids. Chemometric methods were then used to screen potential chemical markers. Furthermore, HJ is effective in hepatoprotective functions. Therefore, hepatocellular-carcinoma-related differentially expressed genes were obtained using bioinformatics, and the corresponding proteins were molecularly docked with diagnostic chemical markers. In total, 78 volatile oils and 63 flavonoids were tentatively identified. The results allowed the selection of 11 metabolites (5 volatile oils and 6 flavonoids), which are nominated as novel markers for material authentication of Taiju and Duoju. Additionally, two proteins associated with hepatoma were screened using bioinformatics. All six flavonoid markers with binding energies of <-5 kcal mol-1 were considered to be anti-hepatoma biomarkers. Noticeably, in Taiju, the content of hydroxygenkwanin showed a downward trend, but the content of the other five flavonoids and the five flavored volatile difference compounds had an upward trend. This bestows a unique flavor profile on Taiju, leading to differences in sensory aroma and clinical efficacy in Taiju and Duoju. In conclusion, the transformation of secondary metabolites was the dominant trend during HJ growth. These findings lay the foundation for food development and distinguishing clinical applications.

12.
Chem Biodivers ; 19(12): e202200748, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36369642

RESUMO

Tyrosinase inhibitors can alleviate the harm to the liver caused by tyrosinase. How to effectively screen out natural tyrosinase inhibitors becomes a focus. In this study, Isodon excisoides was first extracted with the ultrasound optimized by response surface methodology. Then, a method combined ultrafiltration with ultra-liquid chromatography mass spectrometry (UHPLC/MS) was built to screen and identify tyrosinase inhibitors. The binding energies of active ingredients to tyrosinase were calculated by molecular docking. The reliability of the results was validated by the IC50 of enzyme inhibition assay. As a result, the binding energies of 7 components including excisanin B, lasiokaurin, rabdophyllin G, rabdoserrin B, rabdosin D, rabdosinate and weisiensin were lower than that of resveratrol. It was indicated that these components had high tyrosinase inhibitory activity. The IC50 values of lasiokaurin and excisanin B were 177 and 142 µmol/mL, which were less than that of resveratrol (183 µmol/mL). It showed that this way was simple, rapid, reliable and effective, which provided a new strategy to screen natural bioactive compounds from plants.


Assuntos
Isodon , Monofenol Mono-Oxigenase , Simulação de Acoplamento Molecular , Cromatografia Líquida de Alta Pressão/métodos , Isodon/metabolismo , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Resveratrol , Ultrafiltração/métodos , Reprodutibilidade dos Testes
13.
Hum Exp Toxicol ; 41: 9603271221119178, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35984423

RESUMO

Drug-induced nephrotoxicity is widespread and seriously affects human health. Vancomycin is a classical glycopeptide antibiotic. Vancomycin is widely used for severe infections caused by Gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus but its obvious nephrotoxicity affects the safety of its clinical application. However, the etiology of vancomycin induced kidney injury is not well understood. This study aimed to explore the potential mechanism of vancomycin-induced nephrotoxicity in rats. Vancomycin (400 mgkg-1) was used to establish kidney injury models in rats. A metabonomic approach was employed using ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) to delineate metabolic alterations. As a result, 15, 22, and 37 biomarkers were identified in urine samples from the treatment group compared to the control model on D2, D4, and D7, respectively. Changes in the levels of these metabolites indicated that amino acid metabolism and energy metabolism were disturbed in rats with vancomycin-associated nephrotoxicity. This study revealed the kidney effect of vancomycin, which may provide novel and promising research approaches to vancomycin-induced renal toxicity.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Vancomicina , Animais , Biomarcadores/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Humanos , Espectrometria de Massas/métodos , Metabolômica/métodos , Staphylococcus aureus Resistente à Meticilina/metabolismo , Ratos , Vancomicina/toxicidade
15.
Biomed Chromatogr ; 36(10): e5439, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35778888

RESUMO

To evaluate the effect of imrecoxib on CYP2C11 enzyme activity, mRNA, and protein expression, a UPLC method was established. Tolbutamide was selected as the CYP2C11 enzyme-specific probe drug and incubated with imrecoxib in rat liver microsomes. The yield of 4-hydroxytolbutamide was measured using UPLC to investigate the effect of imrecoxib on CYP2C11 enzyme activity. Imrecoxib (10 mg/kg) was administered intragastrically twice daily. After 1, 7, and 14 days of administration, the liver tissues were analyzed. The expression of CYP2C11 enzyme mRNA was determined using reverse transcription-polymerase chain reaction, and its protein expression was determined using Western blot analysis. Imrecoxib concentration was inversely proportional to the production of 4-hydroxytolbutamide in liver microsomes. Imrecoxib demonstrated a dose-dependent inhibitory effect on CYP2C11 activity with IC50 = 74.77 µM. After administration, reverse transcription-polymerase chain reaction showed CYP2C11 enzyme mRNA expressions were 65% (P < 0.05), 35%, and 34% of the control group, respectively (P < 0.01). Western blot analysis showed CYP2C11 enzyme protein expressions were 80, 37, and 34% of the control group, respectively (P < 0.01). Imrecoxib can reduce mRNA and protein expression of CYP2C11 enzyme in rat liver and inhibit the activity of CYP2C11 enzyme in a dose-dependent manner. However, it does not produce clinically significant drug interactions.


Assuntos
Hidrocarboneto de Aril Hidroxilases , Pirróis , Animais , Hidrocarboneto de Aril Hidroxilases/metabolismo , Família 2 do Citocromo P450/genética , Família 2 do Citocromo P450/metabolismo , Microssomos Hepáticos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Mensageiro/farmacologia , Ratos , Esteroide 16-alfa-Hidroxilase/genética , Esteroide 16-alfa-Hidroxilase/metabolismo , Sulfetos
16.
J Sep Sci ; 45(15): 2819-2832, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35638750

RESUMO

Peimine, one of the major quality markers in Fritillaria Cirrhosae Bulbus, was expected to become a new anti-asthma drug. However, its metabolic profiles and anti-asthma mechanism have not been clarified previously. In this study, a method was developed for the detection of peimine metabolites in vitro by ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry. The potential anti-asthma mechanism was predicted by an integrated analysis of network pharmacology and molecular docking. A total of 19 metabolites were identified with the aid of software and molecular networking. The metabolic profiles of peimine elucidated that the metabolism was a multi-pathway process with characteristics of species difference. The network pharmacology results showed that peimine and its metabolites could regulate multiple asthma-related targets. The above targets were involved in various regulatory pathways linked to asthma. Moreover, the results of molecular docking showed that both peimine and its metabolites had a certain affinity with the ß2 adrenergic receptor. The results provided not only important references to understand the metabolism and pharmacodynamic changes of peimine in vitro, but also supporting data for further pharmacological evaluation. It also provided a new perspective for clarifying the functional changes of traditional Chinese medicine in vitro.


Assuntos
Antiasmáticos , Cevanas , Medicamentos de Ervas Chinesas , Antiasmáticos/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Simulação de Acoplamento Molecular , Farmacologia em Rede
17.
Mol Biol Rep ; 49(8): 7337-7345, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35585377

RESUMO

BACKGROUND: The mechanism by which MSC-CM protects neuronal cells against ischemic injury remains to be elucidated. In this study, we aimed to clarify the protective effect of umbilical cord-derived mesenchymal stem cell conditioned medium (UC-MSC-CM) on neuronal oxidative injury and its potential mechanism. METHODS AND RESULTS: Neuronal oxidative damage was mimicked by H2O2 treatment of the HT22 cell line. The numbers of cleaved-Caspase-3-positive cells and protein expression of Caspase-9 induced by H2O2 treatment were decreased by UC-MSC-CM treatment. Furthermore, SOD protein expression was increased in the MSC-CM group compared with that in the H2O2 group. The H2O2-induced TRPM2-like currents in HT22 cells were attenuated by MSC-CM treatment. In addition, H2O2 treatment downregulated the expression of p-JNK protein in HT22 cells, and this the downward trend was reversed by incubation with MSC-CM. CONCLUSIONS: UC-MSC-CM protects neurons against oxidative injury, possibly by inhibiting activation of TRPM2 and the JNK signaling pathway.


Assuntos
Células-Tronco Mesenquimais , Canais de Cátion TRPM , Meios de Cultivo Condicionados/metabolismo , Meios de Cultivo Condicionados/farmacologia , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Sistema de Sinalização das MAP Quinases , Células-Tronco Mesenquimais/metabolismo , Neurônios/metabolismo , Estresse Oxidativo , Canais de Cátion TRPM/genética , Canais de Cátion TRPM/metabolismo , Cordão Umbilical
18.
Biomed Chromatogr ; 36(8): e5409, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35562325

RESUMO

A specific ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) method has been described for the simultaneous determination of the metabolites of tacrine, bupropion, diclofenac, dextromethorphan and midazolam, which are the five probe drugs of the five cytochrome P450 (CYP450) isoforms CYP1A2, CYP2B, CYP2C11, CYP2D1 and CYP3A4. The inhibition degree was determined by calculating the IC50 . The chromatographic separation was performed on a C18 column with a mobile phase consisting of 0.1% formic acid and acetonitrile. The mass spectrometric analysis was conducted in positive electrospray ionization mode. The IC50 values of CYP1A2, CYP2B, CYP2C11, CYP2D1 and CYP3A were 113.4, 83.78, 22.50, 9.081 and 52.76 µmol L-1 , respectively. The in vitro results demonstrated that vindoline could inhibit CYP2D1 activity in rats, and weak inhibitory effect on CYP2C11 and CYP3A, but had no obvious effects on CYP1A2 and CYP2B.


Assuntos
Citocromo P-450 CYP1A2 , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida de Alta Pressão/métodos , Citocromo P-450 CYP3A/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Isoformas de Proteínas , Ratos , Espectrometria de Massas em Tandem/métodos , Vimblastina/análogos & derivados
19.
J Pharm Biomed Anal ; 214: 114692, 2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35279450

RESUMO

This study investigated the inhibitory effect of epirubicin combined with berberine on MCF-7 cell proliferation and explored intracellular pharmacokinetics. A CCK-8 assay was used to detect the inhibitory effect of epirubicin alone and in combination with berberine on MCF-7 cell proliferation in vitro. A rapid and sensitive LC-MS/MS method was developed and validated to detect epirubicin in MCF-7 cells. After incubation with epirubicin and berberine at different time points, MCF-7 cells were lysed and precipitated by acetonitrile to extract the analyte. Chromatographic separation was performed on a C18 column. Daunorubicin was selected as the internal standard. The analytical method was applied to determine the epirubicin concentration in MCF-7 cells. Berberine was found to enhance the inhibitory effect of epirubicin (1 µg/mL and 2 µg/mL) on the proliferation of MCF-7 cells (P < 0.05). LC-MS/MS analysis revealed that berberine significantly increased epirubicin concentration in MCF-7 cells at 8, 12, and 24 h (P < 0.05). The results suggest that berberine may enhance the inhibitory effect of epirubicin on cell proliferation by increasing the concentration of epirubicin in MCF-7 cells. The assay provides a basis for research on the intracellular pharmacokinetics of epirubicin and develops analytical methods for other cell-targeted drugs.


Assuntos
Berberina , Berberina/química , Cromatografia Líquida , Epirubicina/farmacologia , Humanos , Células MCF-7 , Espectrometria de Massas em Tandem/métodos
20.
Phytochem Anal ; 33(4): 517-532, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35144310

RESUMO

INTRODUCTION: The diterpenoids are the most important active constituents that contribute to the pharmacological efficacy of Isodon serra (Maxim.) Hara. Clinical studies have revealed that diterpenoids possess multiple features, e.g. antitumour, antitubercular and anti-ischemic activities. Therefore, the identification and detection of diterpenoids may be equally important for understanding the pharmacological basis of diterpenoids and enhancing the product quality control of I. serra. OBJECTIVES: The purpose of this study was to develop a practical analysis approach of rapid characterisation using ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) for the structure characterisation of the ent-kaurane diterpenoids from I. serra. METHODOLOGY: The analytical strategy was as follows: first, ent-kaurane diterpenoids were detected by a novel on-line data acquisition approach, i.e. sequential window acquisition of all theoretical fragment-ion spectra (SWATH). Second, the MS of eight ent-kaurane diterpenoids was explored, and their mass spectrum cleavage pathways were summarised and determined. Finally, the methanol extract of I. serra was studied using SWATH and identified by extracted ion chromatography (XIC). RESULTS: Compared to the traditional information-dependent acquisition (IDA) method, SWATH significantly improved the hit rate of ent-kaurane diterpenoids. With support from UHPLC separation and specific detection by tandem mass spectrometry (MS/MS), 48 ent-kaurane diterpenoids were successfully characterised and classified as ent-kaurane diterpenoids from a complex matrix. CONCLUSIONS: These combined qualitative methods were used to provide a potential approach for the characterisation of traditional Chinese medicine (TCM) and its preparations. Meanwhile, the SWATH provided a novel and reliable method for the structural characterisation of ent-kaurane diterpenoids from other complicated TCMs.


Assuntos
Diterpenos do Tipo Caurano , Diterpenos , Isodon , Cromatografia Líquida de Alta Pressão , Diterpenos/análise , Diterpenos do Tipo Caurano/análise , Isodon/química , Espectrometria de Massas em Tandem/métodos
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