RESUMO
OBJECTIVE: To delve into the primary active ingredients and mechanism of Pueraria lobata for alleviating iron overload in alcoholic liver disease. METHODS: Pueraria lobata's potential targets and signaling pathways in treating alcohol-induced iron overloads were predicted using network pharmacology analysis. Then, animal experiments were used to validate the predictions of network pharmacology. The impact of puerarin or genistein on alcohol-induced iron accumulation, liver injury, oxidative stress, and apoptosis was assessed using morphological examination, biochemical index test, and immunofluorescence. Key proteins implicated in linked pathways were identified using RT-qPCR, western blot analysis, and immunohistochemistry. RESULTS: Network pharmacological predictions combined with animal experiments suggest that the model group compared to the control group, exhibited activation of the MAPK/ERK signaling pathway, suppression of hepcidin expression, and aggravated iron overload, liver damage, oxidative stress, and hepatocyte death. Puerarin and genistein, the active compounds in Pueraria lobata, effectively mitigated the aforementioned alcohol-induced effects. No statistically significant disparities were seen in the effects above between the two groups receiving drug therapy. CONCLUSION: This study preliminarily demonstrated that puerarin and genistein in Pueraria lobata may increase hepcidin production to alleviate alcohol-induced iron overload by inhibiting the MAPK/ERK signaling pathway.
Assuntos
Sobrecarga de Ferro , Isoflavonas , Hepatopatias Alcoólicas , Sistema de Sinalização das MAP Quinases , Pueraria , Pueraria/química , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/tratamento farmacológico , Hepatopatias Alcoólicas/patologia , Animais , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/metabolismo , Isoflavonas/farmacologia , Isoflavonas/química , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Genisteína/farmacologia , Genisteína/química , Camundongos , Apoptose/efeitos dos fármacosRESUMO
Plants use a dual defense system to cope with microbial pathogens. The first involves pathogen-associated molecular pattern-triggered immunity which is conferred by membrane receptors, and the second involves effector-triggered immunity (ETI), which is conferred by disease-resistance proteins (nucleotide-binding leucine-rich repeat-containing proteins; NLRs). Calmodulin-Binding Protein 60 (CBP60) family transcription factors are crucial for pathogen defense: CBP60g and Systemic Acquired Resistance Deficient 1 (SARD1) positively regulate immunity, whereas CBP60a negatively regulates immunity. The roles of other Arabidopsis (Arabidopsis thaliana) CBP60s remain unclear. We report that CBP60b positively regulates immunity and is redundant with-yet distinct from-CBP60g and SARD1. By combining chromatin immunoprecipitation-PCRs and luciferase reporter assays, we demonstrate that CBP60b is a transcriptional activator of immunity genes. Surprisingly, CBP60b loss-of-function results in autoimmunity, exhibiting a phenotype similar to that of CBP60b gain-of-function. Mutations at the ENHANCED DISEASE SUSCEPTIBILITY 1-PHYTOALEXIN DEFICIENT 4-dependent ETI pathway fully suppressed the defects of CBP60b loss-of-function but not those of CBP60b gain-of-function, suggesting that CBP60b is monitored by NLRs. Functional loss of SUPPRESSOR OF NPR1-1, CONSTITUTIVE 1, an R-gene, partially rescued the phenotype of cbp60b, further supporting that CBP60b is a protein targeted by pathogen effectors, that is, a guardee. Unlike CBP60g and SARD1, CBP60b is constitutively and highly expressed in unchallenged plants. Transcriptional and genetic studies further suggest that CBP60b plays a role redundant with CBP60g and SARD1 in pathogen-induced defense, whereas CBP60b has a distinct role in basal defense, partially via direct regulation of CBP60g and SARD1.
Assuntos
Arabidopsis/genética , Arabidopsis/microbiologia , Proteínas de Ligação a Calmodulina/genética , Proteínas de Ligação a Calmodulina/metabolismo , Doenças das Plantas/imunologia , Imunidade Vegetal/genética , Fatores de Transcrição/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Variação Genética , Genótipo , Pseudomonas syringae/patogenicidadeRESUMO
CONTEXT: Tadehagi triquetrum (Linn.) Ohashi (Fabaceae) (TT), is a traditional herbal medicine used especially in China's ethnic-minority communities, such as the Zhuang, Dai, Li and Wa aeras. As an ethnic medicine, it has long been used to treat various diseases. OBJECTIVE: This review summarised the phytochemical and pharmacological progress on TT from 1979 to October, 2021 by highlighting its chemical classification, structural features, pharmacological applications and folk applications to provide inspirations and suggestions for accelerating further research of this traditional phytomedicine. METHODS: The information on TT in this article has been obtained using these multiple scientific databases including Scifinder, Web of Science, ScienceDirect, Wiley, ACS publications, Springer, PubMed, China Knowledge Resource Integrated Database from the China National Knowledge Infrastructure (CNKI), Google Scholar and Baidu Scholar. Some information was also collected from classic literature on traditional Chinese medicines. RESULTS: More than 70 compounds have been isolated and reported from TT to date by the comprehensive analysis of the current literature. A large number of traditional uses and pharmacological studies have exhibited diversified bioactivities of various TT extracts and its metabolites, including anti-inflammatory, antimicrobial, anti-hepatitis B virus, hepatoprotective, insecticidal, etc. CONCLUSIONS: As a famous traditional medicine with a long history, TT has various medicinal uses and some of them have been supported by modern pharmacological researches. Further detailed studies on the action mechanisms, pharmacodynamics and structure-function relationships of single compounds or active constituents from TT are also required.
Assuntos
Fabaceae , Fitoterapia , China , Etnofarmacologia , Medicina Tradicional ChinesaRESUMO
The development of pollen is a prerequisite for double fertilization in angiosperms. Coat protein complex II (COPII) mediates anterograde transport of vesicles from the endoplasmic reticulum to the Golgi. Components of the COPII complex have been reported to regulate either sporophytic or gametophytic control of pollen development. The Arabidopsis (Arabidopsis thaliana) genome encodes five Sar1 isoforms, the small GTPases essential for COPII formation. By using a dominant negative approach, Sar1 isoforms were proposed to have distinct cargo specificity despite their sequence similarity. Here, we examined the functions of three Sar1 isoforms through analysis of transfer DNA insertion mutants and CRISPR/Cas9-generated mutants. We report that functional loss of Sar1b caused malfunction of tapetum, leading to male sterility. Ectopic expression of Sar1c could compensate for Sar1b loss of function in sporophytic control of pollen development, suggesting that they are interchangeable. Functional distinction between Sar1b and Sar1c may have resulted from their different gene transcription levels based on expression analyses. On the other hand, Sar1b and Sar1c redundantly mediate male gametophytic development such that the sar1b;sar1c microspores aborted at anther developmental stage 10. This study uncovers the role of Sar1 isoforms in both sporophytic and gametophytic control of pollen development. It also suggests that distinct functions of Sar1 isoforms may be caused by their distinct transcription programs.
Assuntos
Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/genética , Transporte Biológico/genética , Pólen/crescimento & desenvolvimento , Pólen/genética , Regulação da Expressão Gênica de Plantas , Genes de PlantasRESUMO
OBJECTIVE: The goal of this study was to investigate the effects of cupric citrate (CuCit) on growth performance, antioxidant indices, serum lipid metabolites, serum immune indices, and tissue residues of copper (Cu), zinc, and iron in weaned pigs. METHODS: A total of 180 weaned pigs (Duroc×Landrace×Large White) with an average body weight of 8.98±1.21 kg were randomly assigned to a corn-soybean meal control ration, or 4 similar rations with 30, 60, 120, or 240 mg/kg Cu as CuCit. All diets contained 10 mg/kg Cu as cupric sulfate from the vitamin-mineral premix. The experiment was divided into two phases: 0 to 14 d (phase 1) and 15 to 28 d (phase 2). RESULTS: Average daily gain (ADG; linearly, p<0.01) and average daily feed intake (ADFI; linearly and quadratically, p<0.05) were affected by an increase in CuCit during phase 2. Overall period, ADG (p<0.05) and ADFI (p<0.01) were linearly increased with increasing dietary levels of CuCit. Serum malondialdehyde concentrations (p<0.05) and glutathione peroxidase activity (p<0.01) linearly decreased and increased respectively with an increase in CuCit. Serum levels of Cu-Zn superoxide dismutase were linearly affected with an increase in CuCit (p<0.01). Hepatic malondialdehyde levels decreased with an increase in CuCit (linearly and quadratically, p<0.01). Serum total cholesterol concentrations were quadratically affected (p<0.05) and decreased in pigs fed Cu as CuCit at 60 and 120 mg/kg and increased in pigs fed 240 mg/kg Cu as CuCit. Serum high-density lipoprotein concentrations were linearly affected with an increase in CuCit (p<0.01). Serum IL-1ß levels were quadratically affected (p<0.05) by dietary treatment. Compared with other treatments, 240 mg/kg Cu from CuCit quadratically increased hepatic (p<0.01) and renal (p<0.05) Cu concentrations, and quadratically decreased hepatic and renal iron concentrations (p<0.05). CONCLUSION: Cu administered in the form of CuCit at a dosage range of 30 to 60 mg/kg, effectively enhanced the growth performance and antioxidant status of weaned pigs.
RESUMO
The study aims to explore the main differential characteristics of Phragmites Rhizoma and its counterfeits (rhizomes of Arundo donax, Triarrhena lutarioriparia and Miscanthus sinensis) and provide experimental basis for the reasonable applications of gramineous plants through system research and comparison of plant morphogenesis, character, transverse organization characteristics and powder microscopic characteristics.
Assuntos
Medicamentos de Ervas Chinesas/normas , Poaceae/química , Rizoma/química , Plantas Medicinais/químicaRESUMO
Objective: To investigate the constituents from the fruit dregs of Rhus chinensis. Methods: The constituents were isolated and purified by chromatography on silica gel,Sephadex LH-20,RP-C18 and Pre-TLC and recrystalization. The structures were identified on the basis of the chemical evidence,spectroscopic data. Results: Ten compounds were obtained and elucidated as m-digalloyl acid( 1),ethyl-m-digallate( 2),apigenin( 3),kaempferol( 4),quercetin( 5),3,7-dimethoxy-5,3',4'-trihydroxy-flavone( 6),quercitrin( 7),kaempferol-3-O-α-L-rhamnoside( 8),myricetrin( 9) and quercetin-3-O-( 4â³-methoxy)-α-L-rahmnopyranosyl( 10),respectively. Conclusion: Compounds 1 ~ 3,6 ~ 10 are separated from the Rhus genus for the first time.
Assuntos
Rhus , Cromatografia , Flavonas , Frutas , Ácido Gálico/análogos & derivados , Glicosídeos , Quempferóis , Quercetina/análogos & derivadosRESUMO
OBJECTIVE: To isolate and elucidate the constituents from the fruit dregs of Rhus chinensis. METHODS: The constituents were isolated and purified by chromatography on silica gel,Sephadex LH-20, RP-C18 gel and recrystallization. The structures were elucidated on the basis of the chemical evidence and spectroscopic data. RESULTS: Ten compounds were obtained: ß-sitosterol (1), morolic acid (2), (2S) -1-O-heptatriacontanoyl glycerol (3), α-monpalmitin (4), palmitic acid (5), gallic acid (6), methyl gallate (7), ethyl gallate (8), propyl gallate (9), and protocatechuic acid (10). CONCLUSION: Compounds 3, 4 and 9 are isolated from the plants of Rhus genus for the first time.
Assuntos
Frutas/química , Rhus/química , Ácido Gálico/análogos & derivados , Sitosteroides , TriterpenosRESUMO
OBJECTIVE: To explore the component difference of the serum containing essential oil from Yin Teng Gu Bi Kang prescription in pathologic and physiologic rat models, and to reveal the material basis of its efficacy of activating blood circulation. METHODS: The essential oils were obtained by CO2 supercritical fluid extraction and the ingredients of the essential oils in vitro and in vivo (under physiological and pathological status) were analyzed by GC-MS to compare differences of the essential oil under physiological and pathological status in rats. RESULTS: 32 components were identified with the main components of Z-ligustilide (39.23%) and d-limonene (21.7%) in the essential oil. In vivo analysis on the essential oil indicated that 16 components were identified, 7 existed originally in essential oil and 9 were metabolites under physiological status; while 22 components were identified, 10 existed originally in essential oil and 12 were metabolites under pathological status (acute blood stasis). There were 7 common prototypes and 8 common metabolites under different physiological status. CONCLUSION: The absorption and metabolism of essential oils were affected by blood stasis and the compounds migrating to blood may be the effective substance in activating blood circulation.
Assuntos
Circulação Sanguínea/efeitos dos fármacos , Óleos Voláteis/farmacologia , 4-Butirolactona/análogos & derivados , Animais , Cromatografia com Fluido Supercrítico , Cicloexenos , Cromatografia Gasosa-Espectrometria de Massas , Limoneno , Ratos , TerpenosRESUMO
Two previously undescribed dibenzocyclooctadiene lignans, named sieverlignans D-E (1-2), as well as eight known ones (3-10), were isolated from the aerial parts of Artemisia sieversiana. Their structures were elucidated from extensive spectroscopic analysis, including HRMS, NMR and electronic circular dichroism (ECD) experiments. This study is the first to report dibenzocyclooctadiene lignans in the genus Artemisia and this plant. All the compounds were evaluated for their anti-neuroinflammatory activities on the lipopolysaccharides (LPS)-induced nitric oxide production in BV-2 murine microglial cells. Compounds 1 and 6 exhibited the moderate activities with their IC50 values of 47.7 and 21.9 µM, compared to a positive control quercetin with the IC50 value of 16.0 µM.
Assuntos
Artemisia , Lignanas , Animais , Anti-Inflamatórios/farmacologia , Ciclo-Octanos , Lignanas/farmacologia , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido NítricoRESUMO
OBJECTIVE: To study metabolic rule in rats for heartleaf houttuynia herb injection and Sodium New Houttuyfonate injection. METHODS: The GC-MS was used to determine metabolites in plasma and urine of rats after intravenous and oral administration of heartleaf houttuynia herb injection as multi-component and Sodium New Houttuyfonate injection as single component. RESULTS: For rats 8 common metabolites were determined in plasma after intravenous administration of heartleaf houttuynia herb injection and Sodium New Houttuyfonate injection, meanwhile 39 in urine. The 16 common metabolites were determined in plasma after oral administration, and 12 in urine. The 9 and 11 of same metabolites were determined in plasma and urine respectively after intravenous and oral administration of heartleaf houttuynia herb injection, 8 and 17 common metabolites for Sodium New Houttuyfonate injection. CONCLUSION: The metabolites of heartleaf houttuynia herb and Sodium New Houttuyfonate injection in rats are the same or similar after intravenous and oral administration, and there are the same structure types between metabolites and original constituents of preparations. The metabolic pathways of the two preparations in rats are the same. There is metabolic Network Compatibility in organism between multi-components, single components and different administration forms for traditional Chinese medicine.
Assuntos
Aldeídos/metabolismo , Anti-Inflamatórios não Esteroides/metabolismo , Medicamentos de Ervas Chinesas/metabolismo , Saururaceae/química , Administração Oral , Aldeídos/administração & dosagem , Aldeídos/sangue , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/sangue , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Infusões Intravenosas , Masculino , Redes e Vias Metabólicas , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
Twenty-four compounds were isolated from the roots of Polygonatum cyrtonema Hua, including a new octopamine dimer, named trans-bis(N-feruloyl)octopamine (1). The structure was established on the basis of spectroscopic and chemical methods. All the extracts and compounds were evaluated for cytotoxic and antioxidant activities by using MTT and chemiluminescence assay. The extracts showed activity against MCF-7 and HepG-2 cell lines from IC50 0.30 to 1.01 mg mL-1. Compound 3 exhibited activity against HepG-2 cell lines with IC50 8.99 µM. Compound 7 exhibited activity against Hela cell lines with IC50 2.53 µM and BGC-823 cell lines with IC50 7.77 µM. Moreover, compound 7 showed antioxidant with IC50 12 µM compared to the positive control with IC50 77 µM. Compound 16 exhibited activity against HepG-2 cell lines with IC50 1.05 µM and MCF-7 cell lines with IC50 1.89 µM. These results indicated that this plant might be potential in natural medicine and healthy food.
Assuntos
Antineoplásicos/isolamento & purificação , Antioxidantes/isolamento & purificação , Polygonatum/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Células Hep G2 , Humanos , Concentração Inibidora 50 , Células MCF-7 , Extratos Vegetais/química , Raízes de Plantas/químicaRESUMO
In the present work, we reported the triterpenoids isolated from n-butanol fraction of Kadsura heteroclita which is a Tujia ethnomedicine with trivial name "Xuetong". This effort resulted in the isolation of six unpresented triterpenoids xuetongsu A-F (1-6), along with five known triterpenoids (7-11). The structures of the reported compounds were established on the 1D, and 2D NMR and HRESIMS spectra, along with CD spectroscopic analysis. Moreover, the absolute stereochemistry of compound 7 was determined by X-ray diffraction analysis. Antioxidant and cytotoxic activities were evaluated for all isolated compounds, compound 7 shown weak cytotoxic activity against HL-60 with IC50 value of 50.0 µM.
Assuntos
Kadsura/química , Caules de Planta/química , Triterpenos/química , China , Células HL-60 , Humanos , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Triterpenos/isolamento & purificaçãoRESUMO
Receptor protein-tyrosine kinases (RPTKs) are tightly regulated during normal cellular processes including cell growth, differentiation, and metabolism. Recently, a RPTK-like molecule named novel oncogene with kinase-domain (NOK) has been cloned and characterized. Overexpression of NOK caused severe cellular transformation as well as tumorigenesis and metastasis in nude mice. In the current study, we generated two tyrosine-->phenylalanine (Y-->F) point mutations (Y327F and Y356F) within the endodomain of NOK that are well conserved in many RPTK subfamilies and are the potential tyrosine phosphorylation sites important for major intracellular signaling. Using BaF3 cells stably expressing the ectodomain of mouse erythropoietin receptor, and the transmembrane and endodomain of NOK (BaF3-E/N), we were able to show that point mutations at either Y327 or Y356 dramatically blocked cellular transformation by NOK as examined by colony formation and cellular DNA synthesis. In addition, tumorigenesis induced by BaF3-E/N was completely abrogated upon the introduction of either single mutation. Importantly, signaling studies revealed that the activation of extracellular signal-regulated kinase was inhibited by Y356F and was significantly reduced by Y327F. Both mutations significantly impaired Akt phosphorylation. Interestingly, both mutations did not affect the kinase activity of NOK. Moreover, apoptotic analysis revealed that both mutations accelerated cell death by activating caspase-3-mediated pathways. Thus, our study shows that these potential tyrosine phosphorylation sites may play critical roles in NOK-mediated tumorigenesis both in vitro and in vivo.
Assuntos
Transformação Celular Neoplásica/genética , Proteínas Oncogênicas/genética , Mutação Puntual , Receptores Proteína Tirosina Quinases/genética , Sequência de Aminoácidos , Animais , Apoptose/genética , Sítios de Ligação , Caspase 3 , Caspases/metabolismo , Processos de Crescimento Celular/genética , Transformação Celular Neoplásica/metabolismo , Sequência Conservada , Ativação Enzimática , Camundongos , Camundongos Nus , Dados de Sequência Molecular , Proteínas Oncogênicas/metabolismo , Fenilalanina/genética , Fosforilação , Receptores Proteína Tirosina Quinases/metabolismo , Alinhamento de Sequência , Transfecção , Tirosina/genéticaRESUMO
A 97-day feeding trial was conducted to investigate the effects of dietary chromium methionine (CrMet) on performance, carcass traits, meat quality, fatty acid profiles of fat, tissue chromium concentrations, and antioxidant status in growing-finishing pigs. A total of 180 crossbred pigs with a mean initial body weight (BW) 30.18 ± 0.28 kg were allotted to 5 treatments with 6 replicates per treatment and 6 pigs per pen in a randomized complete block design based on BW and sex. Treatments were added with 0 (control), 100, 200, 400, and 800 µg/kg chromium as CrMet. Blood samples were obtained from the anterior vena cava on days 97. Carcass characteristics, pork quality, and tissue chromium concentration data were collected from one pig per pen. The results indicated that supplemental CrMet did not significantly affect growth performance, carcass traits, or meat amino acid profiles. Chromium at 100, 400, and 800 µg/kg decreased drip loss but increased shear force (P < 0.05). Pigs fed 100 or 400 µg/kg had a higher 24-h pH than the control (P < 0.05). While meat color, muscle moisture, crude protein, or crude fat were not affected by CrMet. Supplemental 800 µg/kg chromium reduced C18:0 levels in belly fat (P < 0.05), and chromium supplementation increased cis-9, trans 11-conjugated linoleic acid levels linearly (P < 0.05). Dietary CrMet supplementation increased serum, kidney, and muscle chromium contents (P < 0.05) but did not affect liver chromium contents. Besides, tissue chromium concentrations were increased linearly with increased chromium dosage (P < 0.05). Chromium at 400 µg/kg increased serum glutathione peroxidase activities (P < 0.05), and chromium at 800 µg/kg decreased serum total antioxidant capacity levels (P < 0.05). Nevertheless, liver and kidney antioxidant status were not significantly affected by CrMet. These results indicated that dietary supplementation CrMet did not significantly influence growth and carcass traits, but improved meat quality at the expense of tenderness. Therefore, the long-term exposure to 800 µg/kg chromium affected fatty acid compositions and reduced serum antioxidant capacity.
Assuntos
Tecido Adiposo/metabolismo , Antioxidantes/metabolismo , Compostos de Cromo/farmacologia , Cromo/metabolismo , Ácidos Graxos/análise , Crescimento/efeitos dos fármacos , Carne/análise , Metionina/farmacologia , Aumento de Peso/efeitos dos fármacos , Tecido Adiposo/química , Aminoácidos/análise , Ração Animal , Animais , Composição Corporal/efeitos dos fármacos , Cromo/análise , Músculo Esquelético/química , Músculo Esquelético/metabolismo , Sus scrofa , SuínosRESUMO
A novel, simple, and sensitive method based on the use of dispersive micro-solid-phase extraction (d-µ-SPE) procedure combined with ultra-fast liquid chromatography-tandem quadrupole mass spectrometry (UFLC-MS/MS) for the determination of memantine (ME) was developed and validated over the linearity range 0.05-10.0 µg/L with 100 µL of human plasma using memantine-D6 (ME-D6) as the internal standard. The novel nanoring carboxyl-functionalized paramagnetic molecularly imprinted polymer (NR-CF-Mag-MIP) was synthesized by ultrasound-assisted suspension polymerization, using ME as a template molecule, methacrylic acid as a functional monomer, and divinylbenzene as a cross-linking agent. The NR-CF-Mag-MIP was used as the d-µ-SPE sorbent to extract ME from human plasma samples. The obtained results demonstrated the higher extraction capacity of NR-CF-Mag-MIP with recoveries between 97.6 and 101%. The limits of quantification (LOQs) for ME was 0.015 µg/L. Validation results on linearity, specificity, accuracy, precision, and stability, as well as on application to the analysis of samples taken up to 480 h after oral administration of 20 mg (two 10 mg capsules) of ME in healthy volunteers demonstrated the applicability to bioequivalence studies.
Assuntos
Nanopartículas de Magnetita/química , Memantina/análise , Impressão Molecular/métodos , Extração em Fase Sólida/métodos , Cromatografia Líquida de Alta Pressão , Cisteína/análogos & derivados , Cisteína/química , Humanos , Masculino , Memantina/sangue , Metacrilatos/química , Espectrometria de Massas em TandemRESUMO
To study the role of endogenous carbon monoxide (CO) in collagen metabolism during hypoxic pulmonary vascular remodeling, a total of 18 Wistar rats were used in the study and they were randomly divided into three groups: hypoxia group (n = 6), hypoxia with zinc protoporphyrin-IX (ZnPP-IX) group (n = 6) and control group (n = 6). The measurement of mean pulmonary artery pressure (mPAP) and carboxyhemoglobin (HbCO) formation in lung tissue homogenates was measured. A morphometric analysis of pulmonary vessels was performed, in which the percentage of muscularized arteries (MA); partially muscularized arteries (PMA) and nonmuscularized arteries (NMV) in small and median pulmonary vessels, relative medial thickness (RMT) and relative medial area (RMA) of pulmonary arteries were analyzed. Collagen type I and III and transforming growth factor-beta3 (TGF-beta3) expressions were detected by immunohistochemical assay. The expressions of procollagen type I and III and TGF-beta3 mRNA were detected by in situ hybridization. The results showed that ZnPP-IX significantly increased mPAP and markedly decreased HbCO formation in lung tissue homogenates in rats under hypoxia (P < 0.01). In the hypoxia rats treated with ZnPP-IX, the percentage of muscularized arteries of small and median pulmonary vessels was obviously increased, and RMT and RMA of intra-acinar muscularized pulmonary arteries were markedly increased compared with hypoxic rats. Ultrastructural changes, such as hyperplasia and hypertrophy of endothelial cells (ECs) and smooth muscle cells (SMCs) and the increased number of SMCs in synthetic phenotype were found in intra-acinar pulmonary muscularized arteries of hypoxic rats treated with ZnPP-IX. Meanwhile, ZnPP-IX promoted the expression of collagen type I and III and TGF-beta3 protein in pulmonary arteries of rats under hypoxia (P < 0.01). Furthermore, ZnPP-IX elevated obviously the expressions of procollagen type I and III mRNA, and TGF-beta3 mRNA in pulmonary arteries of rats under hypoxia (P < 0.01). The results of this study suggested that ZnPP-IX played an important role in promoting collagen synthesis in pulmonary arteries of rats with hypoxic pulmonary structural remodeling by increasing the expression of TGF-beta3. The above findings also suggested a possible role of endogenous CO in the pathogenesis of chronic hypoxic pulmonary hypertension.
Assuntos
Monóxido de Carbono/fisiologia , Colágeno/biossíntese , Hipóxia/metabolismo , Artéria Pulmonar/metabolismo , Algoritmos , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Monóxido de Carbono/metabolismo , Elasticidade , Inibidores Enzimáticos/farmacologia , Heme Oxigenase (Desciclizante)/antagonistas & inibidores , Imuno-Histoquímica , Hibridização In Situ , Pulmão/anatomia & histologia , Pulmão/metabolismo , Masculino , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Protoporfirinas/farmacologia , Artéria Pulmonar/ultraestrutura , Pressão Propulsora Pulmonar/fisiologia , RNA Mensageiro/biossíntese , Ratos , Ratos Wistar , Fator de Crescimento Transformador alfa/biossínteseRESUMO
The effects of dietary chromium methionine (CrMet) on growth performance, serum metabolites, endocrine parameters, antioxidant status, and immune traits in growing pigs were investigated. A total of 180 crossbred pigs (30.18 ± 0.28 kg initial body mass) were randomly divided into five groups, each group with six pens, six pigs per pen. Pigs were fed on the same basal diet supplemented with 0 (control), 100, 200, 400, and 800 µg/kg Cr from CrMet for 35 days. The results showed that supplemental CrMet did not affect growth performance. Cr at 200-800 µg/kg significantly decreased serum glucose levels (P < 0.05), while other serum metabolites were unaffected by Cr supplementation. Serum growth hormone (GH) levels were significantly decreased by Cr addition (P < 0.05). Furthermore, serum insulin-like growth factor I (IGF-I) levels were linearly decreased with increased Cr dose, and a significant reduction was observed in pigs fed 800 µg/kg Cr diets (P < 0.05). Serum immunoglobulin A, G, and M concentrations were increased linearly with increased Cr dosage, and pigs fed 400 µg/kg Cr had greater serum immunoglobulin M contents (P < 0.05). Cr at 400 µg/kg significantly increased serum superoxide dismutase and total antioxidant capacity activities (T-AOC) (P < 0.05). However, Cr at 800 µg/kg increased serum catalase activities, while decreasing serum T-AOC contents (P < 0.05). Additionally, there was a significant increase in serum malondialdehyde levels for pigs fed 800 µg/kg Cr diets (P < 0.05). These results indicated that dietary supplementation CrMet decreased serum glucose, GH, and IGF-I levels. Besides, supplemental 400 µg/kg Cr as CrMet improved serum antioxidant status and immune responses, but additional 800 µg/kg Cr resulted in lipid peroxidation in growing pigs.
Assuntos
Antioxidantes/metabolismo , Cromo/farmacologia , Metionina/farmacologia , Animais , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/metabolismo , SuínosRESUMO
The liposoluble constituents of leaves (LCL) and stem barks (LCSB) from Acanthopanax evodiaefolius Franch were extracted by Herbal Blitzkrieg Extractor (HBE), and their chemical composition was analyzed by GC-MS. 18 compounds were identified, representing 71.98% of LCL, while 35 compounds were identified, accounting for 98.28% of the LCSB. Their cytotoxic activity and inhibitory effect on nitric oxide (NO) production in LPS-stimulated RAW 264.7 cells were tested and the LCL showed significant NO, IL-6 and TNF-α inhibition activity. These results provide the scientific basis for looking for new natural anti-inflammatory substances and exploiting and developing resources of A. evodiaefolius Franch.
Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Eleutherococcus/química , Macrófagos/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Lipopolissacarídeos/farmacologia , Camundongos , Óxido Nítrico/metabolismo , Casca de Planta/química , Folhas de Planta/química , Caules de Planta/química , Plantas Medicinais/química , Tecnologia Farmacêutica/métodosRESUMO
BACKGROUND: Seventeen million births occur in China each year. Neonatal mortality is the leading cause of under 5-year-old child deaths, and intrapartum-related injury accounts for much of mental retardation in young children. The Chinese Ministry of Health sought to improve infant and child survival through a nationwide initiative to have at least one person trained in neonatal resuscitation at every birth. The aim of the current study was to evaluate the impact of China Neonatal Resuscitation Program (NRP) on policy and infrastructure changes and its effectiveness in decreasing the incidence of mortality among newborn infants. METHODS: The Chinese NRP incorporated policy change, professional education, and creation of a sustainable health system infrastructure for resuscitation. Multidisciplinary teams from all 31 provinces and municipal states disseminated NRP in a train-the-trainer cascade. The intervention targeted 20 provinces with high neonatal mortality and programs to reduce maternal mortality. Program evaluation data came from 322 representative hospitals in those provinces. RESULTS: Changes in policy permitted midwives to initiate resuscitation and required resuscitation training for licensure. From 2004 through 2009 more than 110,659 professionals received NRP training in the 20 target provinces, with 94% of delivery facilities and 99% of counties reached. Intrapartum-related deaths in the delivery room decreased from 7.5 to 3.4 per 10,000 from 2003 to 2008, and the incidence of Apgar ≤ 7 at 1 minute decreased from 6.3% to 2.9%. CONCLUSIONS: The Chinese NRP achieved policy changes promoting resuscitation, trained large numbers of professionals, and contributed to reduction in delivery room mortality. Improved adherence to the resuscitation algorithm, extension of training to the township level, and coverage of births now occurring outside health facilities can further increase the number of lives saved.