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1.
Phytomedicine ; 128: 155362, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38522312

RESUMO

BACKGROUND: Stroke is a leading cause of disability and death worldwide. Currently, there is a lack of clinically effective treatments for the brain damage following ischemic stroke. Catalpol is a bioactive compound derived from the traditional Chinese medicine Rehmannia glutinosa and shown to be protective in various neurological diseases. However, the potential roles of catalpol against ischemic stroke are still not completely clear. PURPOSE: This study aimed to further elucidate the protective effects of catalpol against ischemic stroke. METHODS: A rat permanent middle cerebral artery occlusion (pMCAO) and oxygen-glucose deprivation (OGD) model was established to assess the effect of catalpol in vivo and in vitro, respectively. Behavioral tests were used to examine the effects of catalpol on neurological function of ischemic rats. Immunostaining was performed to evaluate the proliferation, migration and differentiation of neural stem cells (NSCs) as well as the angiogenesis in each group. The protein level of related molecules was detected by western-blot. The effects of catalpol on cultured NSCs as well as brain microvascular endothelial cells (BMECs) subjected to OGD in vitro were also examined by similar methods. RESULTS: Catalpol attenuated the neurological deficits and improved neurological function of ischemic rats. It stimulated the proliferation of NSCs in the subventricular zone (SVZ), promoted their migration to the ischemic cortex and differentiation into neurons or glial cells. At the same time, catalpol increased the cerebral vessels density and the number of proliferating cerebrovascular endothelial cells in the infracted cortex of ischemic rats. The level of SDF-1α and CXCR4 in the ischemic cortex was found to be enhanced by catalpol treatment. Catalpol was also shown to promote the proliferation and migration of cultured NSCs as well as the proliferation of BMECs subjected to OGD insult in vitro. Interestingly, the impact of catalpol on cultured cells was inhibited by CXCR4 inhibitor AMD3100. Moreover, the culture medium of BMECs containing catalpol promoted the proliferation of NSCs, which was also suppressed by AMD3100. CONCLUSION: Our data demonstrate that catalpol exerts neuroprotective effects by promoting neurogenesis and angiogenesis via the SDF-1α/CXCR4 pathway, suggesting the therapeutic potential of catalpol in treating cerebral ischemia.


Assuntos
Quimiocina CXCL12 , Glucosídeos Iridoides , AVC Isquêmico , Neurogênese , Ratos Sprague-Dawley , Receptores CXCR4 , Rehmannia , Animais , Glucosídeos Iridoides/farmacologia , Receptores CXCR4/metabolismo , Neurogênese/efeitos dos fármacos , Quimiocina CXCL12/metabolismo , Masculino , Rehmannia/química , AVC Isquêmico/tratamento farmacológico , Infarto da Artéria Cerebral Média/tratamento farmacológico , Células-Tronco Neurais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ratos , Fármacos Neuroprotetores/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Modelos Animais de Doenças , Transdução de Sinais/efeitos dos fármacos , Células Cultivadas , Angiogênese
2.
Artigo em Inglês | MEDLINE | ID: mdl-38330588

RESUMO

Objective: To improve the understanding of aggressive NK-cell leukemia (ANKL) and summarize the progress of its diagnosis and treatment. Methods: We retrospectively analyzed a case of a patient who was initially diagnosed with T-cell lymphoma (non-specific type) and later transformed into ANKL through examinations such as bone marrow smear, flow cytometry, Q-mNGS, and pathology. We described the patient's diagnostic and treatment journey and conducted a literature review. Results: The patient presented with concomitant hemophagocytic syndrome upon admission. After treatment with the HLH-94 regimen, the patient developed tumor lysis syndrome, leading to a sudden onset of ventricular tachycardia and respiratory and cardiac arrest on the third day of admission. Despite aggressive resuscitation efforts, the patient did not survive. Conclusions: ANKL is rare in the world, and the disease is aggressive, so it is necessary to diagnose early and intervene timely. Bone marrow smear, flow cytometer and Q-mNGS are helpful to identify tumors quickly and determine the direction of diagnosis and treatment. This disease is often accompanied by hemophagocytic syndrome. When the pathogenesis is not clear, it is recommended to treat it with hormone and gamma globulin first, and after clarification, chemotherapy containing L-asparaginase may be added; pay attention to supportive treatment and vigilance against oncolysis. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be performed as soon as possible, and the application of targeted drugs may further improve the curative effect. In a word, ANKL needs more data statistics and analysis to guide clinical diagnosis and treatment.

3.
Food Res Int ; 175: 113713, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38128982

RESUMO

Strip/needle green teas (SGT/NGT) processed using innovative technologies are in high demand; however, mechanisms behind their color and flavor have not been comprehensively studied. We aimed to reveal the dynamics of major pigmented components (carotenoids, lipids, flavonoids, and Maillard products) and their contributions to the flavor of green teas. The total content of flavonoids in SGT and NGT were 255 ± 4.51 and 201 ± 3.91 mg·g-1, respectively; these values are slightly lower than that in fresh leaves (FLs), resulting in a fresh and sweet aftertaste. In average, carotene content in SGT/NGT (24.8 µg·g-1) was higher than in FL (17.4 µg·g-1), whilst xanthophyll content (603 µg·g-1) decreased to one-half of that in FL (310 µg·g-1). Among the 218 primary metabolites, glutamine, glutamic acid, and arginine were found to accumulate and were dominate contributors for the umami and sweet taste. Notably, more than 96 volatiles were screened and revealed their correlations with carotenoids, lipids, and amino acids. Overall, the synergism between pigments and their non-enzymatic derivates' contribution to GT characterized flavor was illustrated.


Assuntos
Camellia sinensis , Chá , Chá/química , Camellia sinensis/química , Flavonoides/análise , Carotenoides , Lipídeos
4.
J Ethnopharmacol ; 319(Pt 3): 117345, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-37926114

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Septic-associated encephalopathy (SAE) is a key manifestation of sepsis. Nevertheless, specific treatment for SAE is still lacking. Catalpol is an active component derived from Rehmanniae Radix, and has been demonstrated to be a potential neuroprotective agent. However, its effect on SAE still needs to be fully explored. AIM: To address the benefits of catalpol on post-sepsis cognitive deterioration and related mechanisms. MATERIALS AND METHODS: Novel object recognition test, temporal order task, histopathology, and immunochemistry were applied to address the benefits of catalpol on LPS-triggered post-sepsis cognitive decline in mice. Xuebijing injection (10 ml/kg) has been utilized as a positive control in the above animal studies. After treatment, the catalpol content in the hippocampus was determined using LC-MS/MS. Finally, the mechanisms of catalpol were further assessed in BV2 and PC12 cells in vitro using Western blot, RT-PCR, flow cytometry, molecular docking tests, thermal shift assay, transmission electron microscopy, and immunofluorescence analysis. RESULTS: Behavior tests showed that catalpol therapy could lessen the cognitive impairment induced by LPS damage. HE, Nissl, immunofluorescence, transmission electron microscopy, and Golgi staining further reflected that catalpol treatment could restore lymphocyte infiltration, blood-brain barrier (BBB) degradation, and the decreasing complexity of dendritic trees. According to LC-MS/MS analysis, catalpol had a 136 ng/mg concentration in the hippocampus. In vitro investigation showed that catalpol could inhibit microglia M1 polarization via blocking NF-κB phosphorylation, translocation and then reducing inflammatory cytokine release in BV2 microglia cells. Brain-derived neurotrophic factor (BDNF) release up-regulation and TrkB pathway activation were observed in the catalpol treatment group in vivo and in vitro. The effect of catalpol on enhancing BDNF expression was inhibited by the specific inhibitor of TrkB (GNF-5837) in PC12 cells. Further molecular docking tests showed that catalpol formed weak hydrophobic bonds with TrkB. Besides, thermal shift assay also reflected that catalpol incubation caused a considerable change in the melting temperature of the TrkB. CONCLUSION: Catalpol alleviates LPS-triggered post-sepsis cognitive impairment by reversing neuroinflammation via blocking the NF-κB pathway, up-regulating neurotrophic factors via the activation of TrkB pathway, and preserving BBB integrity.


Assuntos
Disfunção Cognitiva , Sepse , Ratos , Animais , Camundongos , NF-kappa B , Regulação para Cima , Fator Neurotrófico Derivado do Encéfalo , Lipopolissacarídeos/toxicidade , Cromatografia Líquida , Simulação de Acoplamento Molecular , Doenças Neuroinflamatórias , Espectrometria de Massas em Tandem , Disfunção Cognitiva/tratamento farmacológico
5.
Artigo em Chinês | WPRIM | ID: wpr-973127

RESUMO

Through the textual research and analysis of the variety, origin, processing, quality evaluation and clinical application of Moslae Herba in ancient and modern literature, its origin of materia medica was clarified. Moslae Herba has experienced variety changes in history. Elsholtzia ciliata was the mainstream variety during and before the Song dynasty, however, during the Ming and Qing dynasties, emerging variety of Mosla chinensis rose to the mainstream status due to its remarkable efficacy and the formation of cultivation, and differentiated into two commodities(wild variety of Qingxiangru and cultivated variety of Jiangxiangru), cultivated products formed an authentic producing area in Jiangxi. The three varieties coexisted during the Ming and Qing dynasties, and the Elsholtzia varieties were gradually eliminated. Variety changes have caused changes in the functions and indications of drugs. E. ciliata had the effect of clearing heat and was mainly used to treat heatstroke and cholera, while M. chinensis was used for exogenous wind cold and dampness in the summer because of its warm and strong sweating properties, but not for cholera. Traditional Moslae Herba is mainly harvested in the summer and autumn (flowering to fruiting stage) and the above-ground parts are dry in the shade and used as medicine. Modern Qingxiangru is mostly harvested before the flowering period, and Jiangxiangru is harvested after flowering and fruiting in late summer and early autumn. In summary, according to the 2020 edition of Chinese Pharmacopoeia, the dried above-ground parts of Moslae Herba should be selected for Xinjia Xiangruyin in the Catalogue of Ancient Famous Classical Formulas(The First Batch), mainly the cultivated variety of Jiangxiangru, and the raw products is cut into segments and used as medicine. It is suggested that when applying and developing famous classical formulas containing Moslae Herba at different periods of time today, the origin should be established in conjunction with clinical efficacy.

6.
Zhongguo Zhong Yao Za Zhi ; 47(10): 2681-2688, 2022 May.
Artigo em Chinês | MEDLINE | ID: mdl-35718487

RESUMO

Scutellariae Radix(SR), derived from the dried root of Scutellaria baicalensis in the family Lamiaceae, commonly serves as Chinese medicinal material. Affected by producing areas, growing years, and harvesting periods, the quality of SR fluctuates in the market. However, baicalin≥9% in SR required in the Chinese Pharmacopoeia(2020 edition) can only determine the qualified SR but cannot identify high-quality SR. To improve the quality control methods of SR, the present study analyzed the accumulation of metabolites in SR of different growth years by plant metabolomics, and identified 28 metabolites increasing with growth years(1-3 years). Subsequently, 14 main metabolites were quantitatively analyzed by ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry(UPLC-QQQ-MS). Among them, baicalin, wogonoside, baicalein, and wogonin with high content and good activity were selected as the index components of SR for quality evaluation. A high-performance liquid chromatography(HPLC) method was established to determine the content of four index components in 32 batches of SR from different producing areas, harvesting perio-ds, and growth years. The results showed that the growth years could greatly affect the content of index components. The total content of four index components in 2-year SR was the highest, followed by the 3-/4-year SR and 1-year SR. Based on HPLC data and verification results by enterprises, baicalin ≥12.0%, wogonoside ≥2.3%, baicalein ≥0.1%, and wogonin ≥0.03% were proposed as the evaluation criteria for the high-quality SR. The findings of this study are expected to provide a basis for improving the quality of SR.


Assuntos
Medicamentos de Ervas Chinesas , Flavanonas , Cromatografia Líquida de Alta Pressão/métodos , Flavonoides , Metabolômica , Extratos Vegetais , Scutellaria baicalensis
7.
BMC Plant Biol ; 22(1): 160, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35365087

RESUMO

BACKGROUND: Plant AT-rich sequence and zinc-binding (PLATZ) proteins belong to a novel class of plant-specific zinc-finger-dependent DNA-binding proteins that play essential roles in plant growth and development. Although the PLATZ gene family has been identified in several species, systematic identification and characterization of this gene family has not yet been carried out for Tartary buckwheat, which is an important medicinal and edible crop with high nutritional value. The recent completion of Tartary buckwheat genome sequencing has laid the foundation for this study. RESULTS: A total of 14 FtPLATZ proteins were identified in Tartary buckwheat and were classified into four phylogenetic groups. The gene structure and motif composition were similar within the same group, and evident distinctions among different groups were detected. Gene duplication, particularly segmental duplication, was the main driving force in the evolution of FtPLATZs. Synteny analysis revealed that Tartary buckwheat shares more orthologous PLATZ genes with dicotyledons, particularly soybean. In addition, the expression of FtPLATZs in different tissues and developmental stages of grains showed evident specificity and preference. FtPLATZ3 may be involved in the regulation of grain size, and FtPLATZ4 and FtPLATZ11 may participate in root development. Abundant and variable hormone-responsive cis-acting elements were distributed in the promoter regions of FtPLATZs, and almost all FtPLATZs were significantly regulated after exogenous hormone treatments, particularly methyl jasmonate treatment. Moreover, FtPLATZ6 was significantly upregulated under all exogenous hormone treatments, which may indicate that this gene plays a critical role in the hormone response of Tartary buckwheat. CONCLUSIONS: This study lays a foundation for further exploration of the function of FtPLATZ proteins and their roles in the growth and development of Tartary buckwheat and contributes to the genetic improvement of Tartary buckwheat.


Assuntos
Fagopyrum , Fagopyrum/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Filogenia , Proteínas de Plantas/metabolismo
8.
Acta Pharmacol Sin ; 43(7): 1670-1685, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34795412

RESUMO

Neurovascular unit (NVU) is organized multi-cellular and multi-component networks that are essential for brain health and brain homeostasis maintaining. Neurovascular unit dysfunction is the central pathogenesis process of ischemic stroke. Thus integrated protection of NVU holds great therapeutic potential for ischemic stroke. Catalpol, classified into the iridoid monosaccharide glycoside, is the main active ingredient of the radix from traditional Chinese medicine, Rehmannia glutinosa Libosch, that exhibits protective effects in several brain-related diseases. In the present study, we investigated whether catalpol exerted protective effects for NVU in ischemic stroke and the underlying mechanisms. MCAO rats were administered catalpol (2.5, 5.0, 10.0 mg·kg-1·d-1, i.v.) for 14 days. We showed that catalpol treatment dose-dependently reduced the infarction volume and significantly attenuated neurological deficits score in MCAO rats. Furthermore, catalpol treatment significantly ameliorated impaired NVU in ischemic region by protecting vessel-neuron-astrocyte structures and morphology, and promoting angiogenesis and neurogenesis to replenish lost vessels and neurons. Moreover, catalpol treatment significantly increased the expression of vascular endothelial growth factor (VEGF) through up-regulating PI3K/AKT signaling, followed by increasing FAK and Paxillin and activating PI3K/AKT and MEK1/2/ERK1/2 pathways. The protective mechanisms of catalpol were confirmed in an in vitro three-dimensional NVU model subjected to oxygen-glucose deprivation. In conclusion, catalpol protects NVU in ischemic region via activation of PI3K/AKT signaling and increased VEGF production; VEGF further enhances PI3K/AKT and MEK1/2/ERK1/2 signaling, which may trigger a partly feed-forward loop to protect NVU from ischemic stroke.


Assuntos
AVC Isquêmico , Fator A de Crescimento do Endotélio Vascular , Animais , Glucosídeos Iridoides , Sistema de Sinalização das MAP Quinases , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Fator A de Crescimento do Endotélio Vascular/metabolismo
9.
Sci Rep ; 11(1): 14571, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34272426

RESUMO

Effective and affordable treatments for patients suffering from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are needed. We report in vitro efficacy of Artemisia annua extracts as well as artemisinin, artesunate, and artemether against SARS-CoV-2. The latter two are approved active pharmaceutical ingredients of anti-malarial drugs. Concentration-response antiviral treatment assays, based on immunostaining of SARS-CoV-2 spike glycoprotein, revealed that treatment with all studied extracts and compounds inhibited SARS-CoV-2 infection of VeroE6 cells, human hepatoma Huh7.5 cells and human lung cancer A549-hACE2 cells, without obvious influence of the cell type on antiviral efficacy. In treatment assays, artesunate proved most potent (range of 50% effective concentrations (EC50) in different cell types: 7-12 µg/mL), followed by artemether (53-98 µg/mL), A. annua extracts (83-260 µg/mL) and artemisinin (151 to at least 208 µg/mL). The selectivity indices (SI), calculated based on treatment and cell viability assays, were mostly below 10 (range 2 to 54), suggesting a small therapeutic window. Time-of-addition experiments in A549-hACE2 cells revealed that artesunate targeted SARS-CoV-2 at the post-entry level. Peak plasma concentrations of artesunate exceeding EC50 values can be achieved. Clinical studies are required to further evaluate the utility of these compounds as COVID-19 treatment.


Assuntos
Artemisininas/farmacologia , Extratos Vegetais/farmacologia , SARS-CoV-2/efeitos dos fármacos , Células A549 , Animais , Artemisia annua/química , Chlorocebus aethiops , Humanos , Células Vero , Tratamento Farmacológico da COVID-19
10.
Zhongguo Zhong Yao Za Zhi ; 46(9): 2287-2297, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34047132

RESUMO

Based on the serum medicinal method, this study aims to investigate the migrating components of Yougui Yin in the blood after intragastric administration, and to provide reference for the basic research of its pharmacodynamics. The kidney deficiency rat model was replicated by adenine method. Normal rats and model rats were administered orally for a single gavage of Yougui Yin. The components in blood were rapidly analyzed and identified by ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and multiple reaction monitoring(MRM), and the migrating components in blood of Yougui Yin were explored by multivariate statistical analysis. The results showed that there were 42 characteristic peaks in the plasma of normal rats by UPLC-Q-TOF-MS technology and 13 chemical components were identified, including 6 alkaloids, 2 flavonoids, 2 triterpenoid saponins, 1 iridoid, 1 phenylpropanoid and 1 monoterpenoid. There were 22 characteristic peaks in the plasma of kidney-deficiency rats, and 12 chemical components were identified, including 2 iridoids, 6 alkaloids, 2 flavonoids, 1 monoterpenoid and 1 triterpenoid saponin. Verbascoside, isoacteoside, acteoside, pinoresinoldiglucoside, loganin and morroniside were identified by MRM both in the plasma of normal rats and kidney-deficiency rats. Compared with 85 monomer components in Yougui Yin, 17 common prototype components were found by UPLC-MS in the plasma of normal rats and kidney deficiency rats, including verbascoside, isoacteoside, acteoside, rehmapicrogenin derived from Rehmanniae Radix Praeparata, pinoresinol diglucoside and geniposidic acid from Eucommiea Cortex, loganin and morroniside derived from Corni Fructus, mesaconine, benzoylmesaconine, benzoylaconitine, benzoylhypacoitine, mesaconitine, aconitine derived from Aconiti Lateralis Radix Praeparata, liquiritin, isoliquiritin and glycyrrhizic acid derived from Glycyrrhizae Radix et Rhizoma. Thirty-one metabolites of medicinal ingredients not found in the plasma of adenine-induced kidney deficiency rats were also detected in the plasma of normal rats. Twelve metabolites of medicinal materials not found in the plasma of normal rats were detected in the plasma of kidney deficiency rats. The results of the study provide reference for explaining the material basis and mechanism of Yougui Yin in the treatment of kidney deficiency.


Assuntos
Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Adenina , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Medicamentos de Ervas Chinesas/toxicidade , Glycyrrhiza , Rim , Ratos , Tecnologia
11.
J Sci Food Agric ; 101(14): 6104-6116, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33908040

RESUMO

BACKGROUND: Tartary buckwheat (Fagopyrum tataricum) is a traditional edible and medicinal crop and has been praised as one of the green foods for humans in the 21st century. However, its production and promotion are restricted by the low yields of current varieties. The interaction of genotype and environment could lead to inconsistent phenotypic performance of genotypes across different environments. Climate change has intensified these effects and poses a substantial threat to crop production. RESULTS: In the present study, the effects of meteorological factors on the phenotypic traits of 200 Tartary buckwheat landraces across four macro-environments were investigated. Overall, the phenotypic performance of these Tartary buckwheat landraces was markedly varied across the different environments. Also, the average daily temperature and precipitation had relatively higher impacts on phenotypic performance. The results also revealed the negative impacts of relative humidity on the yield-related traits. Twenty-five Tartary buckwheat landraces were ultimately identified as having good overall phenotypic performance and high yield stability. CONCLUSION: Understanding the impacts of meteorological factors on the phenotypic performance of crops can guide appropriate measures and facilitate germplasm selection for yield enhancement in the context of climate change. The landraces selected comprehensively in this study could be used as parents or intermediate materials for breeding high-quality Tartary buckwheat varieties in the future. The methods used could also be extended to other crops for breeding and germplasm innovation. © 2021 Society of Chemical Industry.


Assuntos
Fagopyrum/crescimento & desenvolvimento , Ecossistema , Meio Ambiente , Conceitos Meteorológicos , Fenótipo , Chuva/química , Temperatura
12.
Zhongguo Zhong Yao Za Zhi ; 46(3): 630-634, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33645029

RESUMO

A new taraxer-based triterpenoid ester, taraxer-14-en-30-al-3ß-O-palmitate(1), was isolated from the whole plant of Wedelia trilobata, along with six known compounds, ent-kaur-16-en-19-oic acid(2), 16α-hydroxy-ent-kauran-19-oic acid(3), tara-xerol(4), ß-amyrin(5), 1ß-acetoxy-4α, 9α-dihydroxy-6ß-isobutyroxyprostatolide(6), and stigmasterol(7). Their structures were elucidated with use of a combination of spectroscopic techniques(IR, HR-ESI-MS, 1 D, 2 D NMR data) and chemical methods.


Assuntos
Triterpenos , Wedelia , Espectroscopia de Ressonância Magnética , Estrutura Molecular
13.
Artigo em Inglês | MEDLINE | ID: mdl-33505489

RESUMO

AIM: To apply the network pharmacology method to screen the target of catalpol prevention and treatment of stroke, and explore the pharmacological mechanism of Catalpol prevention and treatment of stroke. METHODS: PharmMapper, GeneCards, DAVID, and other databases were used to find key targets. We selected hub protein and catalpol which were screened for molecular docking verification. Based on the results of molecular docking, the ITC was used to determine the binding coefficient between the highest scoring protein and catalpol. The GEO database and ROC curve were used to evaluate the correlation between key targets. RESULTS: 27 key targets were obtained by mapping the predicted catalpol-related targets to the disease. Hub genes (ALB, CASP3, MAPK1 (14), MMP9, ACE, KDR, etc.) were obtained in the key target PPI network. The results of KEGG enrichment analysis showed that its signal pathway was involved in angiogenic remodeling such as VEGF, neurotrophic factors, and inflammation. The results of molecular docking showed that ACE had the highest docking score. Therefore, the ITC was used for the titration of ACE and catalpol. The results showed that catalpol had a strong binding force with ACE. CONCLUSION: Network pharmacology combined with molecular docking predicts key genes, proteins, and signaling pathways for catalpol in treating stroke. The strong binding force between catalpol and ACE was obtained by using ITC, and the results of molecular docking were verified to lay the foundation for further research on the effect of catalpol on ACE. ROC results showed that the AUC values of the key targets are all >0.5. This article uses network pharmacology to provide a reference for a more in-depth study of catalpol's mechanism and experimental design.

14.
Chemosphere ; 262: 127807, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32763577

RESUMO

Human hair has been identified as a non-invasive alternative matrix for assessing the human exposure to specific organic contaminants. In the present study, a solvent-saving analytical method for the simultaneous determination of 8 polybrominated diphenyl ethers (PBDEs), 3 hexabromocyclododecanes (HBCDDs), 12 phosphorus flame retardants (PFRs), and 4 emerging PFRs (ePFRs) has been developed and validated for the first time. Hair sample preparation protocols include precleaning with Milli-Q water, digestion with HNO3/H2O2 (1:1, v/v), liquid-liquid extraction with hexane:dichloromethane (4:1, v/v), and fractionation and cleanup on a Florisil cartridge. The method was validated by using two levels of spiked hair samples of 3 replicates for each spiking group. Limits of quantification (LOQs) were 0.12-22.4 ng/g for all analytes, average values of accuracies were ranging between 88 and 115%, 82-117%, 81-128%, and 81-95% for PBDEs, HBCDDs, PFRs, and ePFRs, respectively; and precision was also acceptable (RSD < 20%) for all analytes. Eventually, this method was applied to measure the levels of the targeted analytes in hair samples of e-waste dismantling workers (n = 14) from Qingyuan, South China. Median values ranged between 3.00 and 18.1 ng/g for PBDEs, 0.84-4.04 ng/g for HBCDDs, 2.13-131 ng/g PFRs, and 1.49-29.4 ng/g for ePFRs, respectively. PFRs/ePFRs constitute the major compounds in human hair samples, implying the wide use of PFRs/ePFRs as replacements of PBDEs and HBCDDs, as well the potential high human exposure risks of PFRs/ePFRs. Overall, this work will allow to a comprehensive assessment of human exposure to multiple groups of FRs using hair as a non-invasive bioindicator.


Assuntos
Retardadores de Chama/análise , Cabelo/química , Éteres Difenil Halogenados/análise , Hidrocarbonetos Bromados/análise , China , Monitoramento Ambiental/métodos , Humanos , Peróxido de Hidrogênio/análise , Extração Líquido-Líquido , Fósforo/análise
15.
J Ethnopharmacol ; 246: 112240, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31526861

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: You-Gui-Yin (YGY) is a famous Chinese traditional medicine compound that has been used to treat renal function diseases for more than 300 years. It is recorded in Jing Yue Quanshu, which was written by a famous medical scientist named Jiebing Zhang in the Ming Dynasty. AIM OF THE STUDY: Reproductive dysfunction is one of the most serious complications of chronic kidney disease (CKD). The aim of this study was to observe the effect of You-Gui-Yin (YGY) on reproductive dysfunction of male rats with adenine-induced CKD and to determine if any effects occurred via regulation of the HIF1α-STAT5 pathway. MATERIALS AND METHODS: UPLC-Q-TOF-MS was used to detect the main medicinal components and conduct quality control of YGY. A total of 60 rats were randomly divided into 2 groups: the NC group (10 rats) and the CKD model group (50 rats). The CKD model rats was established by administration of adenine 150 mg kg-1 orally for 14 days. After that, the CKD rats were randomly divided into 5 groups: the CKD group, YGY (10 g kg-1 group, 20 g kg-1 group, 40 g kg-1 group) and the GUI-LU-ER-XIAN-JIAO (GL) 10 g kg-1 group with 10 rats in each group. From the 15th day to the 45th day rats were given 150 mg kg-1 adenine orally every other day to maintain the model (except in the NC group). The YGY groups and the GL group were orally administered the relevant drug once per day for 30 days. The NC group and the CKD group were orally administered an equal volume of normal saline for 30 days. On the 45th day, the rats' sexual behavior index was tested. On the 46th day, the rats were sacrificed. Biochemical indexes, histopathological changes of the kidneys and testes, sperm morphology, sperm abnormality rate, and key proteins in the HIF1α-STAT5 pathway in the kidney and testis were detected. RESULTS: Thirteen components in the YGY extract were identified by UPLC-Q-TOF-MS for quality control of the YGY extract. The results of the biochemical and physiological tests validated the success of inducing CKD accompanied by reproductive dysfunction in rats. YGY significantly retarded the CKD progression and improved the hormone levels of male CKD rats. Sexual behavior tests showed YGY can significantly improve CKD rats' sexual function. In addition, the pathological changes of the kidney and testis, sperm abnormality rate and sperm morphological abnormalities of the CKD rats were reduced by YGY. Furthermore, decreased expression of HIF1α and EPO, and increased expression of p-EPOR (Tyr368), p-JAK2 (Tyr570) and p-STAT5 (Ser725) were observed in the kidney and the testis of the CKD rats. The YGY extract dramatically increased the expression of HIF1α and EPO, and decreased the expression of p-EPOR (Tyr368), p-JAK2 (Tyr570) and p-STAT5 (Ser725) to regulate key proteins in the HIF1α-STAT5 pathway of the kidney and testis. CONCLUSIONS: YGY has obvious reversal effects on the abnormal symptoms of adenine-induced CKD and the abnormal symptoms of rats with hypothyroidism and male reproductive hypotension. Its mechanism is related to its ability to regulate the HIF1α-STAT5 pathway.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Fator de Transcrição STAT5/metabolismo , Comportamento Sexual Animal/efeitos dos fármacos , Animais , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Masculino , Medicina Tradicional Chinesa , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT5/genética , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos
16.
Zhongguo Zhen Jiu ; 39(11): 1160-3, 2019 Nov 12.
Artigo em Chinês | MEDLINE | ID: mdl-31724349

RESUMO

OBJECTIVE: To observe the effect of acupuncture at Renying (ST 9) on morning blood pressure, daytime peak blood pressure and 24-hour blood pressure load in patients with ischemic stroke complicated with essential hypertension. METHODS: A total of 80 patients (3 cases dropped off) were randomized into an observation group (39 cases) and a control group (38 cases). Xingnao Kaiqiao acupuncture and nifedipine were given in the control group. On the basis of treatment in the control group, acupuncture at Renying (ST 9) was applied in the observation group, once a day, 6 times a week for 4 weeks. The changes of morning blood pressure, daytime peak blood pressure and blood pressure load were observed before and after treatment in the two groups. RESULTS: Compared before treatment, morning blood pressure, daytime peak blood pressure and blood pressure load after treatment were reduced in the two groups (all P<0.05). The change of morning systolic pressure in the observation group was not significant as compared with that in the control group (P>0.05); the changes of morning diastolic pressure, daytime peak blood pressure and blood pressure load in the observation group were larger than those in the control group (all P<0.05). CONCLUSION: On the basis of Xingnao Kaiqiao acupuncture and nifedipine, acupuncture at Renying (ST 9) can effectively reduce morning blood pressure, daytime peak blood pressure and blood pressure load in patients with ischemic stroke complicated with essential hypertension.


Assuntos
Terapia por Acupuntura , Isquemia Encefálica , Hipertensão Essencial , Acidente Vascular Cerebral , Pontos de Acupuntura , Terapia por Acupuntura/métodos , Pressão Sanguínea , Hipertensão Essencial/terapia , Humanos , Resultado do Tratamento
17.
J Ethnopharmacol ; 239: 111925, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31055001

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: You-Gui-Yin (YGY) is a traditional Chinese recipe used for reinforcing kidney essence which is recorded in Jingyue Quanshu written by Zhang Jingyue in Ming dynasty. According to traditional Chinese medicine theory, kidney essence is associated with brain and without sufficient kidney essence, cognitive impairment may occur. AIM OF THE STUDY: In this study, we aimed to investigate the effect of YGY extract on cognitive impairment of chronic renal failure (CRF) mice and explore the mechanisms involved. MATERIALS AND METHODS: Aqueous extract of YGY was prepared from crude drugs and was quality controlled by high-performance liquid chromatography (HPLC). CRF was induced by 0.2% adenine in mice and CRF mice were intragastrically administered with 1.5 g kg-1, 3.0 g kg-1, and 6.0 g kg-1 of YGY extract. Mice were identified with CRF by determining several biochemical and physiological indexes, including creatinine clearance rate, serum creatinine, serum urea nitrogen, serum Ca, serum P, serum Mg, body weight and body temperature. Morris water maze and novel object recognition tests were conducted for evaluation of cognitive function. In addition, changes of CaMKIIα/CREB/BDNF and EPO/EPOR pathways in hippocampus were examined by detecting the protein expressions of CaMKIIα, p-CaMKIIα (Thr286), CREB1, p-CREB1 (Ser133), BDNF, EPO, EPOR, p-EPOR (Tyr485), STAT5, and AKT1 using western blotting assays. Also, the primary EPO-producing cells in brain (i.e. astrocytes) and EPO expression regulator HIF-2α were checked by fluorescence microscopy and western blotting assay, respectively. RESULTS: Nine components in YGY extract were figured out and monitored with their contents by HPLC for the quality control of YGY extract. Biochemical and physiological measurements validated the success of induction of CRF in mice, and YGY extract significantly retarded the CRF progression and ameliorated the CRF-induced cognitive impairment. The behavioral tests showed that compared with normal control mice, CRF mice had impaired cognitive function. However, treatment of YGY extract significantly ameliorated the cognitive impairment of CRF mice. Additionally, decreased expressions of hippocampal CaMKIIα, p-CaMKIIα (Thr286), CREB1, p-CREB1 (Ser133), and BDNF were observed in the hippocampus of CRF mice, but YGY extract significantly restored these protein expressions. Moreover, hippocampal EPO, EPOR, p-EPOR (Tyr485), STAT5, AKT1, and HIF-2α, as well as the number of astrocytes in CA1 zone of hippocampus were also decreased in CRF mice, while YGY extract prominently promoted the expressions of these proteins and increased the number of astrocytes. CONCLUSIONS: All the data in this study suggested that YGY extract ameliorated the cognitive impairment of CRF mice, and this amelioration was related to up-regulating the CaMKIIα/CREB/BDNF and EPO/EPOR pathways.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Hipocampo/efeitos dos fármacos , Falência Renal Crônica/tratamento farmacológico , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Eritropoetina/metabolismo , Hipocampo/metabolismo , Falência Renal Crônica/complicações , Falência Renal Crônica/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Receptores da Eritropoetina/metabolismo , Transdução de Sinais/efeitos dos fármacos
18.
Biochem Biophys Res Commun ; 509(3): 822-827, 2019 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-30638657

RESUMO

Dioscorea zingiberensis is a perennial medicinal herb rich in a variety of pharmaceutical steroidal saponins. Squalene epoxidase (SE) is the key enzyme in the biosynthesis pathways of triterpenoids and sterols, and catalyzes the epoxidation of squalene in coordination with NADPH-cytochrome P450 reductase (CPR). In this study, we cloned DzSE and DzCPR gene sequences from D. zingiberensis leaves, encoding proteins with 514 and 692 amino acids, respectively. Recombinant proteins were successfully expressed in vitro, and enzymatic analysis indicated that, when SE and CPR were incubated with the substrates squalene and NADPH, 2,3-oxidosqualene was formed as the product. Subcellular localization revealed that both the DzSE and DzCPR proteins are localized to the endoplasmic reticulum. The changes in transcription of DzSE and DzCPR were similar in several tissues. DzSE expression was enhanced in a time-dependent manner after methyl jasmonate (MeJA) treatments, while DzCPR expression was not inducible.


Assuntos
Dioscorea/enzimologia , NADPH-Ferri-Hemoproteína Redutase/metabolismo , NADP/metabolismo , Proteínas de Plantas/metabolismo , Esqualeno Mono-Oxigenase/metabolismo , Esqualeno/metabolismo , Acetatos/metabolismo , Ciclopentanos/metabolismo , Dioscorea/genética , Dioscorea/metabolismo , Regulação da Expressão Gênica de Plantas , NADPH-Ferri-Hemoproteína Redutase/genética , Oxilipinas/metabolismo , Proteínas de Plantas/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Esqualeno/análogos & derivados , Esqualeno Mono-Oxigenase/genética
19.
Zhongguo Zhong Yao Za Zhi ; 43(20): 4118-4124, 2018 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-30486540

RESUMO

This paper aimed to observe the protective effect of catalpol on the high glucose induced destruction of tight junctions of rat primary brain microvascular endothelial cells (BMECs). Catalpol co-administrated with high glucose increased BMECs survival, decreased its ET-1 secretion, and improved transmembrane electrical resistance in a time-dependent manner. Furthermore, transmission electron microscopy was used to observe catalpol's protective effect on tight junction. Fluorescence staining displayed that catalpol reversed the rearrangement of the cytoskeleton protein F-actin and up-regulated the tight junction proteins claudin-5 and ZO-1, which were further demonstrated by the mRNA expression levels of claudin-5, occludin, ZO-1, ZO-2, ZO-3, α-actintin, vinculin and cateinins. This study indicated that catalpol reverses the disaggregation of cytoskeleton actin in BMECs and up-regulates the expression of tight junction proteins, such as claudin-5, occludin, and ZO-1, and finally alleviates the increase in high glucose-induced BMECs injury.


Assuntos
Citoesqueleto de Actina/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Glucosídeos Iridoides/farmacologia , Junções Íntimas/efeitos dos fármacos , Actinas/metabolismo , Animais , Encéfalo/citologia , Células Cultivadas , Claudina-5/metabolismo , Glucose , Fosfoproteínas , Ratos , Proteína da Zônula de Oclusão-1/metabolismo
20.
Zhongguo Zhong Yao Za Zhi ; 43(24): 4908-4915, 2018 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-30717538

RESUMO

Schisandra chinensis is a commonly used hepatoprotective medicine in clinic. Previous studies have showed that Schisandrae Chinensis Fructus has dual effects on the activity of CYPs. Short-term administration of Schisandrae Chinensis Fructus may inhibit CYP450s activity, while long-term administration may up-regulate CYP activity. High CYP450s activity level may increase the frequency of reactive metabolites-induced liver injury. It remains unclear how long-term administration of Schisandrae Chinensis Fructus may affect acetaminophen-induced acute hepatotoxicity. After oral administration of Schisandrae Chinensis Fructus extract (0.5-2.0 g·kg⁻¹) for 21 d, the activity of CYPs, Nrf2, HO-1, GST expressions, SOD and GST activity as well as glutathione level of SD rats were up-regulated. Besides, Schisandrae Chinensis Fructus extract ameliorated APAP (500 mg·kg⁻¹)-induced acute hepatotoxicity in a dose-dependent manner, as evidenced by decrease in ALT, AST, and MDA level and increase in GSH level (P<0.05). What's more, the liver histopathology was alleviated, and cleaved caspase-3 expression was decreased. Besides, the increase of N-acetyl-p-benzoquinoneimine-GSH (reactive metabolite of acetaminophen) formation was observed in Schisandrae Chinensis Fructus extract groups. In conclusion, the present study indicated that the effects of Schisandrae Chinensis Fructuson acetaminophen-induced hepatotoxicity may rely on the Nrf2 signal pathway activation, and less depends on the increase in CYP450s activity.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas , Acetaminofen , Animais , Sistema Enzimático do Citocromo P-450 , Fígado , Fator 2 Relacionado a NF-E2 , Ratos , Ratos Sprague-Dawley
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