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1.
J Ethnopharmacol ; 282: 114653, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34547420

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: BaZiBuShen formula (BZBS) is clinically used to counteract mental fatigue and to retard the aging process. Brain aging echoes in major risks of human sufferings and has become one of the main challenges to our societies and the health-care systems. AIM OF THE STUDY: To investigate the effect and mode of action of BZBS on aging-associated cognitive impairments. MATERIALS AND METHODS: BZBS was orally administered to D-galactose and NaNO2-induced aging mice. Premature senescence was assessed using the Morris water maze, step-down type passive avoidance, and pole-climbing tests. Telomere length was examined by qPCR analysis. Telomerase activity was assessed using PCR ELISA assay. Mitochondrial complex IV activity was examined by biochemical test. The levels of redox and immune status were determined by ELISA or biochemical assay. The expressions of sirtuin 6 (Sirt6), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), P53, telomerase reverse transcriptase (TERT), heme oxygenase-1 (HO-1), phospho(p)-nuclear factor erythroid-2 related factor 2 (NRF2), caspase-3, Bcl-2 associated x (Bax), and B-cell lymphoma-2 (Bcl-2) in the cerebral cortex were examined by Western blot and/or immunohistochemical staining. RESULTS: BZBS intervention ameliorated reduced brain performances in aging mice, including memory, cognitive, and motor functions. In addition, BZBS administration to aging mice preserved redox homeostasis, attenuated immunosenescence, and maintained telomerase activity and telomere length. Moreover, BZBS treatment were associated with a declines in P53, caspase-3, Bax expressions and an increase in Sirt6, p-HO-1, p-NRF2, PGC-1α, and Bcl-2 expressions in the brains of this rapid aging mouse. CONCLUSIONS: BZBS attenuates premature senescence possibly via the preservation of redox homeostasis and telomere integrity, and inhibition of apoptosis in rapid aging mouse. The mechanism governing the alterations may be associated with through the activation of Sirt6/NRF2/HO-1 and Sirt6/P53-PGC-1α-TERT signaling pathways. The results suggest that BZBS may provide a novel strategy for confronting aging and age-associated diseases.

2.
China CDC Wkly ; 3(32): 681-687, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34594967

RESUMO

What is already known about this topic? The coronavirus disease 2019 (COVID-19) epidemic in China had been effectively controlled for several months, but as the ambient temperature dropped, large gathering-initiated epidemics occurred in northern China, including Hebei, Liaoning, and Jilin provinces. What is added by this report? A sudden epidemic emerged in Wangkui County, Suihua City, Heilongjiang Province, on January 9, 2021. An asymptomatically-infected resident of Harbin City returned from Suihua and triggered a large-scale outbreak in the Zhengda Food Processing Company in Harbin, Heilongjiang. The epidemic was associated with widespread community transmission inside and outside the company, eventually leading to 260 persons being infected (87.8% of 296 patients in Harbin). What are the implications for public health practice? This study demonstrates the importance of screening for infections in the COVID-19 prevention and control system, shares experiences identifying and managing asymptomatic infections, and recommends food processing enterprises like the Zhengda Company to improve preventative measures. Our evidence-based epidemiological analyses provide methods for finding high-risk settings and evaluating epidemic situations when many asymptomatic patients are identified in a short period of time.

4.
Phytomedicine ; 92: 153717, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34583224

RESUMO

BACKGROUND: Radix Ginseng, one of the well-known medicinal herbs, has been used in the management of diabetes and its complications for more than 1000 years. PURPOSE: The aim of this review is devoted to summarize the phytochemistry and pharmacokinetics of Ginseng, and provide evidence for the antidiabetic effects of Ginseng and its ingredients as well as the underlying mechanisms involved. METHODS: For the purpose of this review, the following databases were consulted: the PubMed Database (https://pubmed.ncbi.nlm.nih.gov), Chinese National Knowledge Infrastructure (http://www.cnki.net), National Science and Technology Library (http://www.nstl.gov.cn/), Wanfang Data (http://www.wanfangdata.com.cn/) and the Web of Science Database (http://apps.webofknowledge.com/). RESULTS: Ginseng exhibits glucose-lowering effects in different diabetic animal models. In addition, Ginseng may prevent the development of diabetic complications, including liver, pancreas, adipose tissue, skeletal muscle, nephropathy, cardiomyopathy, retinopathy, atherosclerosis and others. The main ingredients of Ginseng include ginsenosides and polysaccharides. The underlying mechanisms whereby this herb exerts antidiabetic activities may be attributed to the regulation of multiple signaling pathways, including IRS1/PI3K/AKT, LKB1/AMPK/FoxO1, AGEs/RAGE, MAPK/ERK, NF-κB, PPARδ/STAT3, cAMP/PKA/CERB and HIF-1α/VEGF, etc. The pharmacokinetic profiles of ginsenosides provide valuable information on therapeutic efficacy of Ginseng in diabetes. Although Ginseng is well-tolerated, dietary consumption of this herb should follow the doctors' advice. CONCLUSION: Ginseng may offer an alternative strategy in protection against diabetes and its complications through the regulations of the multi-targets via various signaling pathways. Efforts to understand the underlying mechanisms with strictly-controlled animal models, combined with well-designed clinical trials and pharmacokinetic evaluation, will be important subjects of the further investigations and weigh in translational value of this herb in diabetes management.


Assuntos
Diabetes Mellitus , Panax , Plantas Medicinais , Animais , Diabetes Mellitus/tratamento farmacológico , Humanos , Hipoglicemiantes/farmacologia , Fosfatidilinositol 3-Quinases
5.
Zhongguo Zhong Yao Za Zhi ; 46(9): 2363-2369, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34047142

RESUMO

Chinese traditional medicine compound is the main form of Chinese medicine clinical application. The elucidation of the effective components of traditional Chinese medicine is one of the key scientific issues to promote the modernization of traditional Chinese medicine. At present, there are many research ideas on the effective components of traditional Chinese medicine compounds. By analyzing the current status and existing problems of existing research ideas, the author proposes a "double reduction network pharmacology"(2 R network pharmacology) research method based on "prediction of dominant components-potential target selection". Chemical components with good properties were selected by ADMET property prediction technology, and compared with the blood components and target organ components to determine the dominant components with potential therapeutic effect, that is "reducing constituents"; the potential core regulatory pathway of traditional Chinese medicine compound was enriched by RNA-Seq technology combined with network database, and then the target of traditional Chinese medicine compound was mined based on the signal pathway, that is "reducing targets". To improve the efficiency and accuracy of effective component screening, the network relationship of "component target" was established by the related technology of network pharmacology. The purpose of this study is to provide practical research ideas and methods for clarifying the effective components of traditional Chinese medicine, revealing the law of compatibility of traditional Chinese medicine and clarifying the target of drug action.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Bases de Dados Factuais , Medicamentos de Ervas Chinesas/farmacologia , Simulação de Acoplamento Molecular , Projetos de Pesquisa
6.
J Cereb Blood Flow Metab ; 41(9): 2242-2255, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33583260

RESUMO

Neuregulin (NRG)1 - ErbB receptor signaling has been shown to play an important role in the biological function of peripheral microvascular endothelial cells. However, little is known about how NRG1/ErbB signaling impacts brain endothelial function and blood-brain barrier (BBB) properties. NRG1/ErbB pathways are affected by brain injury; when brain trauma was induced in mice in a controlled cortical impact model, endothelial ErbB3 gene expression was reduced to a greater extent than that of other NRG1 receptors. This finding suggests that ErbB3-mediated processes may be significantly compromised after injury, and that an understanding of ErbB3 function would be important in the of study of endothelial biology in the healthy and injured brain. Towards this goal, cultured brain microvascular endothelial cells were transfected with siRNA to ErbB3, resulting in alterations in F-actin organization and microtubule assembly, cell morphology, migration and angiogenic processes. Importantly, a significant increase in barrier permeability was observed when ErbB3 was downregulated, suggesting ErbB3 involvement in BBB regulation. Overall, these results indicate that neuregulin-1/ErbB3 signaling is intricately connected with the cytoskeletal processes of the brain endothelium and contributes to morphological and angiogenic changes as well as to BBB integrity.


Assuntos
Barreira Hematoencefálica/metabolismo , Células Endoteliais/metabolismo , Remodelação Vascular/fisiologia , Animais , Transporte Biológico , Humanos , Masculino , Camundongos , Transfecção
7.
J Diabetes Res ; 2021: 3170190, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33553435

RESUMO

Methods: In this multicenter retrospective study, patients with COVID-19 in China were included and classified into two groups according to whether they were complicated with diabetes or not. Demographic symptoms and laboratory data were extracted from medical records. Univariable and multivariable logistic regression methods were used to explore the risk factors. Results: 538 COVID-19 patients were finally included in this study, of whom 492 were nondiabetes and 46 were diabetes. The median age was 47 years (IQR 35.0-56.0). And the elderly patients with diabetes were more likely to have dry cough, and the alanine aminotransferase, lactate dehydrogenase, Ca, and mean hemoglobin recovery rate were higher than the other groups. Furthermore, we also found the liver and kidney function of male patients was worse than that of female patients, while female cases should be paid more attention to the occurrence of bleeding and electrolyte disorders. Moreover, advance age, blood glucose, gender, prothrombin time, and total cholesterol could be considered as risk factors for COVID-19 patients with diabetes through the multivariable logistic regression model in our study. Conclusion: The potential risk factors found in our study showed a major piece of the complex puzzle linking diabetes and COVID-19 infection. Meanwhile, focusing on gender and age factors in COVID-19 patients with or without diabetes, specific clinical characteristics, and risk factors should be paid more attention by clinicians to figure out a targeted intervention to improve clinical efficacy worldwide.


Assuntos
COVID-19/complicações , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Hospitalização , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais
8.
J Ethnopharmacol ; 271: 113833, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33465437

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Si-Miao-Yong-An decoction (SMYAD), a classical traditional Chinese medicine (TCM) formula, has been used to treat various cardiovascular diseases in clinics. AIM OF THE STUDY: The aim of this study is to investigate the effective combinatorial components from SMYAD and its mechanism regarding the intervention on myocardial hypertrophy. MATERIALS AND METHODS: SMYAD constituents absorbed in rat plasma and heart were identified using UHPLC Q-Exactive-Orbitrap MS/MS. The identified constituents in SMYAD were further analyzed using ADMET (absorption, distribution, metabolism, excretion and toxicity) prediction and molecular docking. The effective constituents were identified using isoproterenol (ISO)-induced H9c2 cardiomyocyte hypertrophy, and neochlorogenic acid (NCA), chlorogenic acid (CA), cryptochlorogenic acid (CCA), isochlorogenic acid C (ICAC), angoroside C (AGDC), isochlorogenic acid A (ICAA), sweroside (SRD), and harpagide (HPD) in SMYAD extract were quantified by HPLC for compatibility. Finally, anti-hypertrophic activities of candidate effective combinatorial components, which were prepared according to the determined molar concentration ratio of effective constituents using reference substance solution, were analyzed using immunofluorescence staining and Quantitative real-time PCR. The expression levels of PI3Kα, p-ERK, p-Akt, Akt, p-mTOR, mTOR and HIF-1α were measured using Western blot. RESULTS: 32 prototypes of SMYAD were identified from plasma and heart tissue of rat. Combining with ADMET prediction, 31 dominant constituents were focused. Based on HIF-1 pathway identified in preliminary result, 17 targets were focused, which were used to dock with 31 constituents. 27 constituents were therefore hit as the potential effective constituents of SMYAD in inhibiting myocardial hypertrophy. Bioactivity evaluation showed that NCA, CA, CCA, ICAC, AGDC, ICAA, SRD, and HPD significantly inhibited the increase of H9c2 cell surface area induced by ISO. Except for ICAA and AGDC, the remaining 6 effective constituents, showing a certain inhibitory effect on ISO-induced ANP mRNA overexpression at high and low concentrations, participated in compatibility based on the molar concentration ratio determined by HPLC. Effective combinatorial components composed of the 6 effective constituents (effective combinatorial components ABC) showed significant inhibitory effect on the increase of cell surface area, and the overexpression of ANP and ß-MHC mRNA in H9c2 cells induced by ISO. Moreover, effective combinatorial components ABC significantly inhibited the protein overexpressions of p-Akt, p-mTOR and HIF-1α. Based on the results, we put forward the strategy of "Focusing constituents" and "Focusing targets" for the effective constituents research of TCM formula. CONCLUSION: Effective combinatorial components ABC composed of NCA, CA, CCA, ICAC, SRD and HPD from SMYAD inhibited ISO-induced cardiomyocyte hypertrophy and down-regulated expression of ANP and ß-MHC mRNA through the inactivation of Akt/mTOR/HIF-1α pathway.


Assuntos
Cardiomegalia/tratamento farmacológico , Cardiomegalia/metabolismo , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Animais , Fator Natriurético Atrial/genética , Linhagem Celular , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Isoproterenol/toxicidade , Masculino , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Cadeias Pesadas de Miosina/genética , Fosfatidilinositol 3-Quinase/metabolismo , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Plasma/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Serina-Treonina Quinases TOR/metabolismo
9.
PLoS One ; 15(12): e0244125, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33332437

RESUMO

BACKGROUND: A worldwide outbreak of coronavirus disease (COVID-19), since 2019, has brought a disaster to people all over the world. Many researchers carried out clinical epidemiological studies on patients with COVID-19 previously, but risk factors for patients with different levels of severity are still unclear. METHODS: 562 patients with laboratory-confirmed COVID-19 from 12 hospitals in China were included in this retrospective study. Related clinical information, therapies, and imaging data were extracted from electronic medical records and compared between patients with severe and non-severe status. We explored the risk factors associated with different severity of COVID-19 patients by logistic regression methods. RESULTS: Based on the guideline we cited, 509 patients were classified as non-severe and 53 were severe. The age range of whom was 5-87 years, with a median age of 47 (IQR 35.0-57.0). And the elderly patients (older than 60 years old) in non-severe group were more likely to suffer from fever and asthma, accompanied by higher level of D-dimer, red blood cell distribution width and low-density lipoprotein. Furthermore, we found that the liver and kidney function of male patients was worse than that of female patients in both severe and non-severe groups with different age levels, while the severe females had faster ESR and lower inflammatory markers. Of major laboratory markers in non-severe cases, baseline albumin and the lymphocyte percentage were higher, while the white blood cell and the neutrophil count were lower. In addition, severe patients were more likely to be accompanied by an increase in cystatin C, mean hemoglobin level and a decrease in oxygen saturation. Besides that, advanced age and indicators such as count of white blood cell, glucose were proved to be the most common risk factors preventing COVID-19 patients from aggravating. CONCLUSION: The potential risk factors found in our study have shown great significance to prevent COVID-19 patients from aggravating and turning to critical cases during treatment. Meanwhile, focusing on gender and age factors in groups with different severity of COVID-19, and paying more attention to specific clinical symptoms and characteristics, could improve efficacy of personalized intervention to treat COVID-19 effectively.


Assuntos
COVID-19 , SARS-CoV-2/metabolismo , Índice de Gravidade de Doença , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , COVID-19/sangue , COVID-19/epidemiologia , Criança , Pré-Escolar , China/epidemiologia , Surtos de Doenças , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais
10.
Biomed Pharmacother ; 132: 110817, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33068937

RESUMO

BACKGROUND: Diabetic cardiomyopathy (DCM) is a main cause of heart failure and death in diabetic patients. However, countermeasures to limit the development of this disease remain insufficient. Si-Miao-Yong-An decoction (SMYA), a Chinese herbal prescription, exhibits both lipid-lowering and cardiovascular preserving effects, and may have an effect on DCM management. PURPOSE: The current study is aimed to investigate the effects of SMYA on the cardiac function in diabetic mice and the underlying mechanisms involved. METHODS: Streptozotocin-induced diabetic mice were fed intragastrically with SMYA every day for 15 weeks. Cardiac function was assessed by echocardiograph. Histopathological alterations in the heart were determined by hematoxylin/eosin, wheat germ agglutinin, Masson's trichrome, Terminal dUTP nick end-labeling, Oil red O staining, and transmission electron microscopy. The potential involvements of GLC/AMPK/NF-κB and GLC/PPARα/PGC-1α signaling pathways were investigated by western blot and/or immunohistochemical staining. RESULTS: Treatment of diabetic mice with SMYA improved insulin sensitivity, and attenuated the increases of water consumption, food intake, blood glucose, and serum GLC. Furthermore, SMYA ameliorated cardiac systolic and diastolic functions, suppressed the myocardial hypertrophy, fibrosis, apoptosis, inflammation, and lipid accumulation as well as preserved the myofilaments arrangement and mitochondrial integrity. Finally, SMYA downregulated the expressions of GCGR, PGC-1α, PPARα and the phosphorylation of NF-κB, as well as upregulated the phosphorylation of AMPK in the hearts of diabetic mice. CONCLUSIONS: SMYA may ameliorate glucolipid metabolism and cardiac function through the regulation of GLC/AMPK/NF-κB and GLC/PPARα/PGC-1α signaling pathways in diabetic mice, suggesting that this prescription could provide a new source of drug candidates to protect against DCM.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Cardiomiopatias Diabéticas/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/fisiopatologia , Glucagon/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , PPAR alfa/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estreptozocina
11.
Food Funct ; 11(10): 8743-8756, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-32955050

RESUMO

Salvianolic acid B (Sal B) exhibits anti-obesity activity, yet the underlying mechanism linking this effect to metabolic endotoxemia remains unexplored. For this purpose, high-fat diet-induced obese mice were orally administered with Sal B for 10 weeks. Hematoxylin/eosin staining, transmission electron microscopy, and immunohistochemical staining were used to evaluate histopathological alterations in the white adipose tissue (WAT) and/or jejunums. The expression levels of genes related to fat and cholesterol synthesis in the WAT were determined by qPCR. The composition of fecal microbiota was profiled by 16S rRNA gene pyrosequencing. Western blotting was employed to evaluate the relative protein expressions involved in lipopolysaccharide (LPS)/toll-like receptor 4 (TLR4) signaling pathway in the WAT. Treatment of obese mice with Sal B improves insulin sensitivity, attenuates body weight gain and alleviates serum levels of LPS and tumor necrosis factor alpha, which is associated with an improvement in intestinal epithelial integrity and probiotic composition as well as a reduction in Gram-negative Proteobacteria and Deferribacteres. In addition, Sal B downregulates the expressions of TLR4 and myeloid differential factor-88, as well as the phosphorylation levels of Jun N-terminal kinase, nuclear factor-kappa B p65, and an insulin receptor substrate in the WAT. In summary, Sal B may attenuate body weight gain and insulin resistance through the regulation of gut microbiota abundances and LPS/TLR4 signaling pathway in obese mice, suggesting Sal B could be a promising drug candidate for protection against obesity.


Assuntos
Fármacos Antiobesidade/farmacologia , Benzofuranos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Ganho de Peso/efeitos dos fármacos , Administração Oral , Animais , Dieta Hiperlipídica/efeitos adversos , Lipopolissacarídeos/metabolismo , Camundongos , Camundongos Obesos , Obesidade/etiologia , Receptor 4 Toll-Like/metabolismo
12.
Stroke ; 51(9): 2844-2853, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32772683

RESUMO

BACKGROUND AND PURPOSE: Although VEGF165 (vascular endothelial growth factor-165) is able to enhance both angiogenesis and neurogenesis, it also increases vascular permeability through the blood-brain barrier. Heparan sulfate (HS) sugars play important roles in regulating VEGF bioactivity in the pericellular compartment. Here we asked whether an affinity-purified VEGF165-binding HS (HS7) could augment endogenous VEGF activity during stroke recovery without affecting blood-brain barrier function. METHODS: Both rat brain endothelial cell line 4 and primary rat neural progenitor cells were used to evaluate the potential angiogenic and neurogenic effects of HS7 in vitro. For in vivo experiments, male Sprague-Dawley rats were subjected to 100 minutes of transient focal cerebral ischemia, then treated after 4 days with either PBS or HS7. One week later, infarct volume, behavioral sequelae, immunohistochemical markers of angiogenesis and neural stem cell proliferation were assessed. RESULTS: HS7 significantly enhanced VEGF165-mediated angiogenesis in rat brain endothelial cell line 4 brain endothelial cells, and increased the proliferation and differentiation of primary neural progenitor cells, both via the VEGFR2 (vascular endothelial growth factor receptor 2) pathway. Intracerebroventricular injection of HS7 improved neurological outcome in ischemic rats without changing infarct volumes. Immunostaining of the compromised cerebrum demonstrated increases in collagen IV/Ki67 and nestin/Ki67 after HS7 exposure, consistent with its ability to promote angiogenesis and neurogenesis, without compromising blood-brain barrier integrity. CONCLUSIONS: A VEGF-activating glycosaminoglycan sugar, by itself, is able to enhance endogenous VEGF165 activity during the post-ischemic recovery phase of stroke.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Heparitina Sulfato/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Heparitina Sulfato/administração & dosagem , Infarto da Artéria Cerebral Média/prevenção & controle , Injeções Intraventriculares , Ataque Isquêmico Transitório/tratamento farmacológico , Ataque Isquêmico Transitório/fisiopatologia , Masculino , Neovascularização Fisiológica/efeitos dos fármacos , Células-Tronco Neurais/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Fator A de Crescimento do Endotélio Vascular/administração & dosagem , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
13.
Curr Drug Metab ; 21(12): 979-993, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32735517

RESUMO

OBJECTIVE: To study the compatibility regularity of Simiao Yong'an decoction by determining the plasma protein binding rate with the constituents in Simiao Yong'an decoction and to preliminarily clarify the effects of the compatibility on the plasma protein binding rate of different components. METHODS: Based on the equilibrium dialysis method, high-performance liquid chromatography was used to determine the contents of six constituents, which were divided into a single group and combination groups, in Simiao Yong'an decoction in the internal and external dialysis solutions. The obtained plasma protein binding rate through calculations was an index to evaluate the binding of the above components to plasma protein in different conditions. RESULTS: Harpagide, harpagoside, sweroside and loganin showed low plasma protein binding rates, ferulic acid exhibited a moderate plasma protein binding rate, and glycyrrhizic acid showed a high plasma protein binding rate. The compatibility study showed that glycyrrhizic acid promoted the binding of ferulic acid to plasma protein. Glycyrrhizic acid and ferulic acid were the key compounds to promote the binding of harpagide to plasma protein. Glycyrrhizic acid, harpagide, harpagoside and loganin had a significant inhibitory effects on the binding of sweroside to plasma protein. The plasma protein binding capacities of harpagoside and loganin were reduced by the other five constituents. Glycyrrhizic acid had the strongest plasma protein binding effect, and the binding effect was not affected by other components. CONCLUSION: This study explores the effects of compound compatibility on effective components from the perspective of plasma protein binding by high-performance liquid chromatography combined with the equilibrium dialysis method, and lays a foundation for clarifying the compatibility rule of Simiao Yong'an decoction and also provides a new idea for the study of the compatibility of traditional Chinese medicine formulas.


Assuntos
Ácidos Cumáricos/metabolismo , Glicosídeos/metabolismo , Ácido Glicirrízico/metabolismo , Iridoides/metabolismo , Piranos/metabolismo , Soroalbumina Bovina/metabolismo , Cromatografia Líquida de Alta Pressão , Compostos Fitoquímicos/metabolismo , Ligação Proteica
14.
Nature ; 582(7812): 395-398, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32494010

RESUMO

Neuroprotectant strategies that have worked in rodent models of stroke have failed to provide protection in clinical trials. Here we show that the opposite circadian cycles in nocturnal rodents versus diurnal humans1,2 may contribute to this failure in translation. We tested three independent neuroprotective approaches-normobaric hyperoxia, the free radical scavenger α-phenyl-butyl-tert-nitrone (αPBN), and the N-methyl-D-aspartic acid (NMDA) antagonist MK801-in mouse and rat models of focal cerebral ischaemia. All three treatments reduced infarction in day-time (inactive phase) rodent models of stroke, but not in night-time (active phase) rodent models of stroke, which match the phase (active, day-time) during which most strokes occur in clinical trials. Laser-speckle imaging showed that the penumbra of cerebral ischaemia was narrower in the active-phase mouse model than in the inactive-phase model. The smaller penumbra was associated with a lower density of terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL)-positive dying cells and reduced infarct growth from 12 to 72 h. When we induced circadian-like cycles in primary mouse neurons, deprivation of oxygen and glucose triggered a smaller release of glutamate and reactive oxygen species, as well as lower activation of apoptotic and necroptotic mediators, in 'active-phase' than in 'inactive-phase' rodent neurons. αPBN and MK801 reduced neuronal death only in 'inactive-phase' neurons. These findings suggest that the influence of circadian rhythm on neuroprotection must be considered for translational studies in stroke and central nervous system diseases.


Assuntos
Relógios Circadianos/fisiologia , Ritmo Circadiano/fisiologia , Modelos Animais de Doenças , Neurônios/patologia , Neuroproteção , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/prevenção & controle , Animais , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Isquemia Encefálica/prevenção & controle , Glucose/deficiência , Humanos , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/fisiopatologia , Infarto da Artéria Cerebral Média/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oxigênio , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Acidente Vascular Cerebral/fisiopatologia , Pesquisa Médica Translacional , Falha de Tratamento
15.
Nature ; 583(7814): E14, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32533095

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

16.
Biomed Pharmacother ; 127: 110132, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32403042

RESUMO

BACKGROUND: Myocardial fibrosis is an important pathological feature of pressure overload cardiac remodeling. Si-Miao-Yong-An decoction (SMYAD), a traditional Chinese formula, is now clinically used in the treatment of cardiovascular diseases in China. However, its mechanisms in the prevention of heart failure are not fully revealed. PURPOSE: To determine whether treatment with SMYAD for 4 weeks would lead to changes in collagen metabolism and ventricular remodeling in a mice model of heart failure. METHODS: Mice were subjected to transverse aorta constriction to generate pressure overload induced cardiac remodeling and then were administered SMYAD (14.85 g/kg/day) or captopril (16.5 mg/kg/day) intragastrically for 4 weeks after surgery. Echocardiography and immunohistochemical examination were used to evaluate the effects of SMYAD. The mRNA of collagen metabolism biomarkers were detected. Protein expression of TGF-ß1/Smad and TGF-ß1/TAK1/p38 pathway were assessed by Western blot. RESULTS: SMYAD significantly improved cardiac function, increased left ventricle ejection fraction, and decreased fibrosis area and αSMA expression. Moreover, SMYAD reduced proteins expression related to collagen metabolism, including Col1, Col3, TIMP2 and CTGF. The increased levels of TGF-ß1, Smad2, and Smad3 phosphorylation were attenuated in SMYAD group. In addition, SMYAD reduced the levels of TGF-ß1, p-TAK1 and p-p38 compared with TAC group. CONCLUSIONS: SMYAD improved cardiac fibrosis and heart failure by inhibition of TGF-ß1/Smad and TGF-ß1/TAK1/p38 pathway. SMYAD protected against cardiac fibrosis and maintained collagen metabolism balance by regulating MMP-TIMP expression. Taken together, these results indicate that SMYAD might be a promising therapeutic agent against cardiac fibrosis.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Metaloproteinases da Matriz/metabolismo , Miocárdio/patologia , Inibidores Teciduais de Metaloproteinases/metabolismo , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Animais , Colágeno/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Fibrose , MAP Quinase Quinase Quinases/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/fisiologia , Fator de Crescimento Transformador beta1/fisiologia , Remodelação Ventricular/efeitos dos fármacos
17.
Front Pharmacol ; 11: 602, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32431617

RESUMO

Hypertrophic scar (HS) is a serious fibrotic skin disease and often considered as a kind of benign skin tumor. Tetramethylpyrazine (TMP), the main chemical composition of the traditional Chinese medicine Chuanxiong Rhizoma, has shown significant clinical benefits in the treatment of fibrosis disease and tumor, while the role in HS and the concrete mechanisms remain elusive. Herein, the protective effects of TMP in the treatment of HS was investigated and the results showed that the protein expression levels of type I collagen (Col I), type III collagen (Col III), and α-smooth muscle actin (α-SMA) were all inhibited remarkably after addition of TMP in HS-derived fibroblasts (HFs). Moreover, TMP also suppressed fibroblast proliferative and induced cell apoptosis. The protein expression levels of Caspase-3 and Bcl-2 were all decreased comparing with the control group while proapoptotic proteins Bax and Cleaved Caspase-3 were increased. In addition, TMP treatment markedly reduced the phosphorylation levels of AKT. Taken together, our investigations demonstrated that TMP could down-regulate the expression of fibrosis-related molecules, inhibit scar fibroblast proliferation and activate cell apoptosis, during which AKT pathway was involved. Thus, this study shed more light on the pharmacological mechanisms of TMP, and provided a novel therapeutic alternative for prevention and treatment of HS.

18.
J Agric Food Chem ; 68(24): 6464-6484, 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32441927

RESUMO

Chlorogenic acids (CGAs) have gained considerable attention as pervasive human dietary constituents with potential cardiovascular-preserving effects. The main sources include coffee, yerba mate, Eucommia ulmodies leaves, and Lonicerae Japonicae Flos. CGA consumption can reduce the risks of hypertension, atherosclerosis, heart failure, myocardial infarction, and other factors associated with cardiovascular risk, such as obesity and type 2 diabetes. This review recapitulates recent advances of CGAs in the cardiovascular-preserving effects, pharmacokinetics, sources, and safety. Emerging evidence indicates that CGAs exhibit circulatory guarding properties through the suppression of oxidative stress, leukocyte infiltration, platelet aggregation, platelet-leukocyte interactions, vascular remodeling, and apoptosis as well as the regulation of glucose and lipid metabolism and vasodilatory action in the cardiovascular system. CGAs exert these effects by acting on complex signaling networks, but the global mechanisms are still not clear. The oral bioavailability of CGA is poor, and there is a potential sensitization concern about CGA. The bioactive metabolites, systematic toxicity, and optimized structure are needed for further identification.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Ácido Clorogênico/administração & dosagem , Diabetes Mellitus Tipo 2/prevenção & controle , Animais , Doenças Cardiovasculares/metabolismo , Ácido Clorogênico/efeitos adversos , Ácido Clorogênico/farmacocinética , Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Humanos
19.
Int J Mol Sci ; 21(3)2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32012810

RESUMO

Recombinant fibroblast growth factor 21 (rFGF21) has been shown to be potently beneficial for improving long-term neurological outcomes in type 2 diabetes mellitus (T2DM) stroke mice. Here, we tested the hypothesis that rFGF21 protects against poststroke blood-brain barrier (BBB) damage in T2DM mice via peroxisome proliferator-activated receptor gamma (PPARγ) activation in cerebral microvascular endothelium. We used the distal middle cerebral occlusion (dMCAO) model in T2DM mice as well as cultured human brain microvascular endothelial cells (HBMECs) subjected to hyperglycemic and inflammatory injury in the current study. We detected a significant reduction in PPARγ DNA-binding activity in the brain tissue and mRNA levels of BBB junctional proteins and PPARγ-targeting gene CD36 and FABP4 in cerebral microvasculature at 24 h after stroke. Ischemic stroke induced a massive BBB leakage two days after stroke in T2DM mice compared to in their lean controls. Importantly, all abnormal changes were significantly prevented by rFGF21 administration initiated at 6 h after stroke. Our in vitro experimental results also demonstrated that rFGF21 protects against hyperglycemia plus interleukin (IL)-1ß-induced transendothelial permeability through upregulation of junction protein expression in an FGFR1 activation and PPARγ activity elevation-dependent manner. Our data suggested that rFGF21 has strong protective effects on acute BBB leakage after diabetic stroke, which is partially mediated by increasing PPARγ DNA-binding activity and mRNA expression of BBB junctional complex proteins. Together with our previous investigations, rFGF21 might be a promising candidate for treating diabetic stroke.


Assuntos
Barreira Hematoencefálica/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Fatores de Crescimento de Fibroblastos/administração & dosagem , PPAR gama/metabolismo , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Células Cultivadas , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Fatores de Crescimento de Fibroblastos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos , Cultura Primária de Células , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/metabolismo , Proteínas de Junções Íntimas/genética , Proteínas de Junções Íntimas/metabolismo
20.
Clin Proteomics ; 16: 38, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31719821

RESUMO

Background: Neuroticism is a core personality trait and a major risk factor for several mental and physical diseases, particularly in females, who score higher on neuroticism than men, on average. However, a better understanding of the expression profiles of proteins in the circulating blood of different neurotic female populations may help elucidate the intrinsic mechanism of neurotic personality and aid prevention strategies on mental and physical diseases associated with neuroticism. Methods: In our study, female subjects were screened for inclusion by the Eysenck Personality Questionnaire (EPQ), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) scales and routine physical examination. Subjects who passed the examination and volunteered to participate were grouped by neuroticism using EPQ scores (0 and 1 = low neuroticism group; > 5 = high neuroticism group). Proteins in serum samples of the two neuroticism groups were identified using isobaric tags for relative and absolute quantification (iTRAQ) technology. Results: A total of 410 proteins exhibited significant differences between high and low neuroticism, 236 proteins were significantly upregulated and 174 proteins were significantly downregulated. Combine the results of GO and KEGG enrichment analysis of differences proteins between high and low neuroticism with the PPI network, it could be observed that the Alpha-synuclein (SNCA), ATP7A protein (ATP7A), Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (GNG2), cyclin-dependent kinase 6 (CDK6), myeloperoxidase (MPO), azurocidin (AZU1), Histone H2B type 1-H (HIST1H2BH), Integrin alpha-M (ITGAM) and Matrix metalloproteinase-9 (MMP9) might participate in the intrinsic mechanism of neuroticism by regulating response to catecholamine stimulus, catecholamine metabolic process, limbic system development and transcriptional misregulation in cancer pathway. Conclusions: Our study revealed the characteristics of the neurotic personality proteome, which might be intrinsic mechanism of the neurotic population.

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