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1.
Artículo en Inglés | MEDLINE | ID: mdl-37691215

RESUMEN

INTRODUCTION: Natural medicine (NM) has been used since ancient times for therapeutic purposes worldwide. Presently, the combination of clopidogrel and NM with a reasonable synergistic effect has gained increasing acceptance in clinical therapeutics. METHODS: Here, we have performed a comprehensive retrieval of literature published in both English and Chinese databases until August 1, 2022, studying the synergistic interactions of clopidogrel and NM through pharmacokinetic/pharmacodynamic (PK-PD) analyses. We retrieved 7, 3, and 5 studies on PK analysis and 3, 3, and 8 studies on PD analysis for the interaction of clopidogrel with single herbal medicines, bioactive compounds, and herbal prescriptions, respectively. Most studies on NM have been found to mainly focus on preclinical observations, and there have been fewer clinical PK analyses. RESULTS: A potential drug-herb interaction has been observed to occur when clopidogrel and NM were metabolized by an enzyme network comprising P-gp, CES1, and CYP450. In contrast, most PD studies have focused on clinical observations, and few preclinical findings have been reported. Some cases have suggested that the combination of the two types of drugs would alter the antiplatelet efficacy and adverse effects. Studies on PK, however, have shown significant or slightly varying results for the drug prototype and its metabolites. CONCLUSION: In the combination therapies, the interaction between clopidogrel and NM was found to alter antiplatelet aggregation pathways and P2Y12 receptor function.

2.
Med Res Arch ; 11(2)2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37502377

RESUMEN

The need for therapeutics to overcome development of existing diseases research to discover new lead agents. In the face of public health challenges worldwide, natural medicines play a pivotal role in innovative lead drug discovery. Network pharmacology can easily construct complicated poly-pharmacology network based on lead compound, biological function, and bioactive target proteins, which meets the overall feature of natural medicines, and enable to elucidate the action mechanism at molecule-protein level with systematic view. In this work, we first summarized the recent progress delineating lead drug development and its interaction with natural medicines. Second, we focused on the relationship between natural medicines and network pharmacology. Additionally, we discussed current issues and potential prospects for the lead drug discover from natural medicines by network pharmacology. Further investigations should be focus on relevant structural analysis for biological experiment, also the dynamic and quantitative network development. In summary, it is a rational approach for innovative lead drug discovery, and with the development of structure and biology research, this approach makes it a very powerful method for the lead molecules in a high-throughput manner from a comprehensive and powerful special multi-compound to target protein/disease poly pharmacology network.

3.
Front Chem ; 10: 941367, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35958230

RESUMEN

Ligustrazine (TMP) is a natural pyrazine alkaloid extracted from the roots of Ligusticum Chuanxiong Hort, which has the potential as an antitumor agent. A series of 33 ligustrazine-heterocycle (TMPH) derivatives were designed, synthesized, and investigated via antitumor screening assays, molecular docking analysis, and prediction of drug-like properties. TMP was attached to other heterocyclic derivatives by an 8-12 methylene alkyl chain as a linker to obtain 33 TMPH derivatives. The structures were confirmed by 1H-NMR, 13C-NMR, and high-resolution mass spectroscopy spectral (HR-MS) data. The antiproliferative activity against human breast cancer MCF-7, MDA-MB-231, mouse breast cancer 4T1, mouse fibroblast L929, and human umbilical vein endothelial HUVEC cell lines was evaluated by MTT assay. Compound 12-9 displayed significant inhibitory activity with IC50 values in the low micromolar range (0.84 ± 0.02 µM against the MDA-MB-231 cell line). The antitumor effects of compound 12-9 were further evaluated by plate cloning, Hoechst 33 342 staining, and annexin V-FITC/PI staining. The results indicated that compound 12-9 inhibited the proliferation and apoptosis of breast cancer cells. Furthermore, molecular docking of compound 12-9 into the active site of the Bcl-2, CASP-3, and PSMB5 target proteins was performed to explore the probable binding mode. The 33 newly synthesized compounds were predicted to have good drug-like properties in a theoretical study. Overall, these results indicated that compound 12-9 inhibited cell proliferation through PSMB5 and apoptosis through Bcl-2/CASP-3 apoptotic signaling pathways and had good drug-like properties. These results provided more information, and key precursor lead derivatives, in the search for effective bioactive components from Chinese natural medicines.

4.
Genes (Basel) ; 12(12)2021 11 26.
Artículo en Inglés | MEDLINE | ID: mdl-34946844

RESUMEN

Transcription factors are key molecules in the regulation of gene expression in all organisms. The transcription factor LEAFY COTYLEDON 2 (LEC2), which belongs to the DNA-binding protein family, contains a B3 domain. The transcription factor is involved in the regulation of important plant biological processes such as embryogenesis, somatic embryo formation, seed storage protein synthesis, fatty acid metabolism, and other important biological processes. Recent studies have shown that LEC2 regulates the formation of lateral roots and influences the embryonic resetting of the parental vernalization state. The orthologs of LEC2 and their regulatory effects have also been identified in some crops; however, their regulatory mechanism requires further investigation. Here, we summarize the most recent findings concerning the effects of LEC2 on plant growth and seed development. In addition, we discuss the potential molecular mechanisms of the action of the LEC2 gene during plant development.


Asunto(s)
Proteínas de Arabidopsis/genética , Cotiledón/crecimiento & desarrollo , Cotiledón/genética , Genes de Plantas/genética , Desarrollo de la Planta/genética , Semillas/genética , Factores de Transcripción/genética , Arabidopsis/genética , Arabidopsis/crecimiento & desarrollo , Regulación del Desarrollo de la Expresión Génica/genética , Regulación de la Expresión Génica de las Plantas/genética , Hojas de la Planta/genética , Hojas de la Planta/crecimiento & desarrollo , Raíces de Plantas/genética , Raíces de Plantas/crecimiento & desarrollo , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/crecimiento & desarrollo , Semillas/crecimiento & desarrollo
5.
Int J Mol Sci ; 22(20)2021 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-34681932

RESUMEN

Pentatricopeptide repeat (PPR) proteins form a large protein family in land plants, with hundreds of different members in angiosperms. In the last decade, a number of studies have shown that PPR proteins are sequence-specific RNA-binding proteins involved in multiple aspects of plant organellar RNA processing, and perform numerous functions in plants throughout their life cycle. Recently, computational and structural studies have provided new insights into the working mechanisms of PPR proteins in RNA recognition and cytidine deamination. In this review, we summarized the research progress on the functions of PPR proteins in plant growth and development, with a particular focus on their effects on cytoplasmic male sterility, stress responses, and seed development. We also documented the molecular mechanisms of PPR proteins in mediating RNA processing in plant mitochondria and chloroplasts.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Desarrollo de la Planta , Proteínas de Plantas/metabolismo , Plantas/metabolismo , Proteínas de Plantas/genética
6.
J Clin Pharm Ther ; 46(5): 1373-1381, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34101878

RESUMEN

WHAT IS KNOWN AND OBJECTIVE: We have previously shown that the saponins of Sanguisorba parviflora (Maxim.) Takeda (Sp. T) relieved cyclophosphamide-induced myelosuppression in leukopenic mice. Haematopoietic cell-specific protein 1-associated protein X-1 (HAX-1) participated in the survival of neutrophils through the regulation of mitochondrial function. The aim of the present study was to comprehensively identify the role of HAX-1 in the mechanism of leukopenia alleviation by Sp. T. METHODS: HAX-1 gene and protein expression levels in peripheral blood neutrophils were examined using real-time quantitative reverse transcription-polymerase chain reaction, western blot and immunohistochemical assays. Neutrophil apoptosis was measured using flow cytometry. Mitochondrial function was determined via assessments of the reactive oxygen species (ROS) generation and mitochondrial membrane potential (ΔΨm) integrity levels. RESULTS AND DISCUSSION: The HAX-1 gene expression level in the peripheral blood neutrophils was significantly lower in patients with leukopenia than in healthy donors. The saponins of Sp. T induced HAX-1 expression and promoted myeloid progenitor cell (mEB8-ER cell) viability. HAX-1 overexpression reduced the production of ROS and maintained ΔΨm integrity. Cyclophosphamide-induced mitochondrial dysfunction and apoptosis could be abrogated by treatment with Sp. T or metformin. WHAT IS NEW AND CONCLUSION: Our data suggest a mechanism through which Sp. T protects against chemotherapy-induced leukopenia by regulating HAX-1 gene expression in a mitochondrial-dependent manner.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/biosíntesis , Ciclofosfamida/efectos adversos , Leucopenia/inducido químicamente , Leucopenia/tratamiento farmacológico , Sanguisorba/química , Saponinas/farmacología , Adulto , Apoptosis/efectos de los fármacos , Femenino , Humanos , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Persona de Mediana Edad , Células Progenitoras Mieloides/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo
7.
J Clin Pharm Ther ; 46(5): 1334-1342, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34075619

RESUMEN

WHAT IS KNOWN AND THE OBJECTIVE: Our previous studies have shown that saponins of Sanguisorba parviflora (Maxim) Takeda (Sp. T) relieved cyclophosphamide-induced myelosuppression in mice with leukopenia. The hematopoietic cell-specific protein 1-associated protein X-1 (HAX-1) participated in the survival of neutrophils through the regulation of mitochondrial function. This study aimed to comprehensively identify the role of HAX-1 in Sp. T to alleviate leukopenia. METHODS: HAX-1 expression was examined in the peripheral blood neutrophils using real-time polymerase chain reaction (PCR), Western blot analysis and immunohistochemical staining. Neutrophil apoptosis was measured by flow cytometry. Mitochondrial function was evaluated via reactive oxygen species (ROS) generation and mitochondrial membrane potential (ΔΨm) integrity. RESULTS AND DISCUSSION: Our study indicated that the expression of the HAX-1 gene was significantly decreased in the peripheral blood neutrophils of leukopenia patients compared with healthy donors. The saponins of Sp. T induced HAX-1 expression and promoted myeloid progenitor cell (mEB8-ER cell) viability, while overexpression of HAX-1 reduced the production of reactive oxygen species (ROS) and maintained the integrity of the mitochondrial membrane potential. Cyclophosphamide-induced mitochondrial dysfunction and apoptosis could be abrogated by treatment with Sp. T or the addition of metformin. WHAT IS NEW AND OUR CONCLUSION: Our data support a mechanism where Sp. T protects against chemotherapy-induced leukopenia by regulating HAX-1 gene expression in a mitochondrial-dependent manner.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/biosíntesis , Ciclofosfamida/efectos adversos , Leucopenia/inducido químicamente , Leucopenia/tratamiento farmacológico , Sanguisorba/química , Saponinas/farmacología , Adulto , Apoptosis/efectos de los fármacos , Femenino , Humanos , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Persona de Mediana Edad , Neutrófilos/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo
8.
Plant Cell Rep ; 40(1): 213-221, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33099669

RESUMEN

KEY MESSAGE: The promoter of the Arabidopsis thaliana ß-glucosidase 19 gene directs GUS expression in a seed-specific manner in transgenic Arabidopsis and tobacco. In the present study, an 898-bp putative promoter of the Arabidopsis ß-glucosidase 19 (AtBGLU19) gene was cloned. The bioinformatics analysis of the cis-acting elements indicated that this putative promoter contains many seed-specific elements, such as RY elements. The features of this promoter fragment were evaluated for the capacity to direct the ß-glucuronidase (GUS) reporter gene in transgenic Arabidopsis and tobacco. Histochemical and fluorometric GUS analyses of transgenic Arabidopsis plants revealed that the AtBGLU19 promoter directed strong GUS activity in late-maturing seeds and dry seeds, whereas no GUS expression was observed in other organs. The results indicated that the AtBGLU19 promoter was able to direct GUS expression in a seed-specific manner in transgenic Arabidopsis. In tobacco, the intensity of the staining and the level of GUS activity were considerably higher in the seeds than in the other tissues. These results further confirmed that the AtBGLU19 promoter is seed specific and can be used to control transgene expression in a heterologous plant system.


Asunto(s)
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Celulasas/genética , Nicotiana/genética , Plantas Modificadas Genéticamente/genética , Regiones Promotoras Genéticas , Semillas/genética , beta-Glucosidasa/genética , Clonación Molecular , Regulación de la Expresión Génica de las Plantas , Glucuronidasa/genética , Secuencias Reguladoras de Ácidos Nucleicos
9.
J Coll Physicians Surg Pak ; 28(12): 937-940, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30501831

RESUMEN

OBJECTIVE: To prepare neogambogic acid nanoliposomes (GNA-NLC) and study its pharmacokinetics (PK) in rats. STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: Mudanjiang Medical University, Mudanjiang, China, from January 2016 to October 2017. METHODOLOGY: GNA-NLC was prepared by emulsion evaporation-low temperature solidification. The entrapment efficiency, average particle size, and zeta potential were investigated. Male Wistar rats were injected with 1 mg/mL gambogic acid and GNA-NLC into the caudal vein respectively, and the plasma concentration was determined by UPLC- MS/MS. The pharmacokinetic parameters of the two agents were compared. RESULTS: GNA-NLC prepared in this study were mostly spherical spheroids with an average particle size of 146.35 ±1.72 nm, polydispersity coefficient of 0.26 ±0.02, zeta potential of -28.24 ±0.13 MV, entrapment efficiency of 84.63%, and drug loading capacity of 4.23%. DSC showed that neogambogic acid nanoparticles had formed and neogambogic acid was amorphous in the matrix. The pharmacokinetics results in rats showed that GNA-NLC plasma concentration was significantly higher than that of common preparation of gambogic acid, with a half-life period of 10.14 ±0.03 hours, 4.57 times that of gambogic acid. AUC0 ~ 24h of gambogic acid in GNA-NLC lipidosome was 58.36 ±0.23 μg/h/mL, 4.83 times that of gambogic acid. CONCLUSION: GNA-NLC can be prepared successfully by emulsion evaporation-low temperature solidification. The method is simple and easy to control. The GNA-NLC has a long cycle, and high blood concentration, sustained release compared with the raw material gambogic acid.


Asunto(s)
Composición de Medicamentos , Xantenos/farmacocinética , Animales , Liposomas , Masculino , Ratas , Ratas Wistar
10.
Molecules ; 23(8)2018 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-30060516

RESUMEN

We report the highly efficient and chemoselective oxidation of benzylic alcohols catalyzed by sodium copper chlorophyllin in water, producing corresponding arylcarbonyl compounds. Importantly, the catalytic system exhibits a wide substrate scope and high functional group tolerance. Moreover, secondary alcohols and even diarylmethanes were smoothly oxidized to the desired aryl ketones with excellent yields.


Asunto(s)
Compuestos de Bencilo/química , Clorofilidas/química , Metano/química , Alcoholes/química , Catálisis , Estructura Molecular , Oxidación-Reducción , Agua/química
11.
Plant Cell Rep ; 35(8): 1757-67, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27215439

RESUMEN

KEY MESSAGE: The bidirectional promoter of the Arabidopsis thaliana gene pair At1g71850/At1g71860 harbors low-temperature-responsive elements, which participate in anti-correlated transcription regulation of the driving genes in response to environmental low temperature. A divergent gene pair is defined as two adjacent genes organized head to head in opposite orientation, sharing a common promoter region. Divergent gene pairs are mainly coexpressed, but some display opposite regulation. The mechanistic basis of such anti-correlated regulation is not well understood. Here, the regulation of the Arabidopsis thaliana gene pair At1g71850/At1g71860 was investigated. Semi-quantitative RT-PCR and Genevestigator analyses showed that while one of the pair was upregulated by exposure to low temperature, the same treatment downregulated the other. Promoter::GUS fusion transgenes were used to show that this behavior was driven by a bidirectional promoter, which harbored an as-1 motif, associated with the low-temperature response; mutation of this sequence produced a significant decrease in cold-responsive expression. With regard to the as-1 motif in the native orientation repressing the promoter's low-temperature responsiveness, the same as-1 motif introduced in the reverse direction showed a slight enhancement in the promoter's responsiveness to low-temperature exposure, indicating that the orientation of the motif was important for the promoter's activity. These findings provide new insights into the complex transcriptional regulation of bidirectional gene pairs as well as plant stress response.


Asunto(s)
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Frío , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Regiones Promotoras Genéticas , Proteínas Tirosina Fosfatasas/genética , Ubiquitina Tiolesterasa/genética , Proteínas de Arabidopsis/metabolismo , Fluorometría , Glucuronidasa/metabolismo , Proteínas Tirosina Fosfatasas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Análisis de Secuencia de ADN , Estrés Fisiológico/genética , Ubiquitina Tiolesterasa/metabolismo
12.
J Integr Plant Biol ; 57(2): 162-70, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25370697

RESUMEN

Bidirectional promoters are relatively abundant in eukaryotic genomes, suggesting that they have an important biological significance. As yet, few of these promoters have been characterized in detail. Here, using a promoter::GUS transgene approach has revealed that the intergenic region of Arabidopsis thaliana divergent genes At1g71850 and At1g71860 is an asymmetric bidirectional promoter, which exhibits an orientation-dependent expression profile. The strength of the forward promoter was greater than that of the reverse promoter, and their tissue specificities were not identical. Deletion analyses revealed that this bidirectional promoter could be divided into three functional regions. The basal level and tissue specificity of the promoter in the reverse orientation were regulated positively by region II and negatively by region III, whereas promoter activity in the forward orientation was regulated negatively by region II and positively by region I. Thus the 52-bp stretch of region II had a dual function, enhancing expression in the reverse orientation and suppressing it in the forward orientation. These results demonstrated that the activity of the At1g71850-At1g71860 bidirectional promoter was modulated by complex interactions between both positive and negative cis-acting elements. These findings will enhance our understanding of the regulatory mechanisms of plant bidirectional promoters.


Asunto(s)
Arabidopsis/genética , Regiones Promotoras Genéticas , ADN Intergénico/genética , Fluorometría , Glucuronidasa/metabolismo , Inmunohistoquímica , Plantas Modificadas Genéticamente , Análisis de Secuencia de ADN , Eliminación de Secuencia
13.
Cancer Res ; 70(23): 9581-90, 2010 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-21098714

RESUMEN

CD4(+)CD25(+)Foxp3(+) T-regulatory cells (Tregs) accumulate in tumors; however, little is known about how the tumor environment influences this process. Here we show that human melanomas express inducible T-cell costimulator ligand (ICOS-L/B7H) that can provide costimulation through ICOS for the expansion of activated Tregs maintaining high Foxp3 and CD25 expression as well as a suppressive function. Thus, ICOS-L expression by melanoma tumor cells may directly drive Treg activation and expansion in the tumor microenvironment as another mechanism of immune evasion.


Asunto(s)
Antígenos CD/metabolismo , Proliferación Celular , Melanoma/metabolismo , Linfocitos T Reguladores/metabolismo , Animales , Antígenos CD/genética , Línea Celular Tumoral , Técnicas de Cocultivo , Citometría de Flujo , Factores de Transcripción Forkhead/metabolismo , Humanos , Ligando Coestimulador de Linfocitos T Inducibles , Interferón gamma/metabolismo , Interleucina-10/metabolismo , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Células L , Activación de Linfocitos/inmunología , Melanoma/genética , Melanoma/patología , Melanoma Experimental/genética , Melanoma Experimental/metabolismo , Melanoma Experimental/patología , Ratones , Ratones Endogámicos C57BL , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Linfocitos T Reguladores/inmunología , Microambiente Tumoral
14.
Sci China C Life Sci ; 46(6): 651-60, 2003 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18758722

RESUMEN

PNZIP gene promoter has been cloned from Pharbitis nil by adaptor PCR, which conforms to eukaryotic promoter characteristic. Primer extension analysis showed that the transcription start site was located 122 nucleotides upstream of the translation start site of PNZIP gene. According to the characteristic of PNZIP promoter, a series of deletions were purposely made by PCR. Five deletion fragments were fused to upstream of GUS gene and transferred into tobacco. Fluorometric GUS assay showed that five different length promoters all could specifically drive GUS gene expression in photosynthetic tissues and their activities decreased along with the gradual deletion of PNZIP promoter. In addition, the activity of full-length promoter was 9 times higher than that of CaMV 35S in leaf. PNZIP promoter may have two putative cis-elements, GAAATA and GATACT, which relate to gene expression in photosynthetic tissues. GATACT may determine the gene specific expression in photosynthetic tissues, while GAAATA, perhaps, as an enhancer, increases the intensity of gene expression.

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