Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 50
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Acta Pharmacol Sin ; 44(9): 1801-1814, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37041228

RESUMO

Liver, as an immune and detoxification organ, represents an important line of defense against bacteria and infection and a vulnerable organ that is easily injured during sepsis. Artesunate (ART) is an anti-malaria agent, that also exhibits broad pharmacological activities including anti-inflammatory, immune-regulation and liver protection. In this study, we investigated the cellular responses in liver to sepsis infection and ART hepatic-protective mechanisms against sepsis. Cecal ligation and puncture (CLP)-induced sepsis model was established in mice. The mice were administered ART (10 mg/kg, i.p.) at 4 h, and sacrificed at 12 h after the surgery. Liver samples were collected for preparing single-cell RNA transcriptome sequencing (scRNA-seq). The scRNA-seq analysis revealed that sepsis-induced a dramatic reduction of hepatic endothelial cells, especially the subtypes characterized with proliferation and differentiation. Macrophages were recruited during sepsis and released inflammatory cytokines (Tnf, Il1b, Il6), chemokines (Ccl6, Cd14), and transcription factor (Nfkb1), resulting in liver inflammatory responses. Massive apoptosis of lymphocytes and abnormal recruitment of neutrophils caused immune dysfunction. ART treatment significantly improved the survival of CLP mice within 96 h, and partially relieved or reversed the above-mentioned pathological features, mitigating the impact of sepsis on liver injury, inflammation, and dysfunction. This study provides comprehensive fundamental proof for the liver protective efficacy of ART against sepsis infection, which would potentially contribute to its clinical translation for sepsis therapy. Single cell transcriptome reveals the changes of various hepatocyte subtypes of CLP-induced liver injury and the potential pharmacological effects of artesunate on sepsis.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Sepse , Camundongos , Animais , Artesunato/uso terapêutico , Células Endoteliais/patologia , Sepse/complicações , Sepse/tratamento farmacológico , Análise de Sequência de RNA
2.
Nat Prod Rep ; 38(7): 1243-1250, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34287440

RESUMO

Covering: Up to 2020 Artemisinin has made a significant contribution towards global malaria control since its initial discovery. Countless lives have been saved by this unique and miraculous molecule. In 2006, artemisinin-based combination therapies (ACTs) were recommended by the World Health Organization (WHO) as the first-line treatment for uncomplicated malaria infection and have since remained as the mainstays of the antimalarial treatment. Even so, substantial efforts to pursue better curative effects for the treatment of malaria have never ceased, particularly with regards to the circumstances surrounding the appearance of delayed clearance of malaria parasites by 3 day ACT treatments in South-East Asian countries. Strategies to further optimize artemisinin-based therapies, including synthesizing better artemisinin derivatives, developing advanced drug delivery systems, and diversifying artemisinin partner drugs, have been proposed over the past few years. Here, we provide an updated account of the continuous efforts in improving ACTs for better efficacy in curing malarial infection.


Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Malária/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Quimioterapia Combinada , Humanos , Estrutura Molecular
3.
Zhongguo Zhong Yao Za Zhi ; 46(19): 4907-4921, 2021 Oct.
Artigo em Zh | MEDLINE | ID: mdl-34738384

RESUMO

Platelet function tests have been increasingly used to assist in the diagnosis of platelet disorders and prethrombotic state, monitoring of the efficacy of antiplatelet therapies, and personalized treatment. On the basis of light transmission aggregometry, new methods for platelet function test have been developed successively. At present, the research and development of platelet function detector is in its infancy in China. The active constituents of antiplatelet Chinese medicines can be classified into terpenoids, flavonoids, saponins, organic acids, lignans, diketones, volatile oils, and stilbenes. The results of dose-antiplatelet effect relationship of Chinese medicines and the active constituents showed that the effective concentration of the extracts or monomers of Chinese medicines was at micromolar level(µmol·L~(-1)), among which salvianolic acid B and ginkgolide K, ginkgolide B, and ginkgolide A had the strongest antiplatelet effect. These results suggest that the antiplatelet effect of Chinese medicine may be weaker than that of chemical drugs and biological products. Therefore, it is necessary to explore the structure-activity relationship of the active constituents in existing Chinese medicines and further improve their efficacy through structure modification. The antiplatelet effect of Chinese medicines and the constituents involves multiple pathways and multiple targets. These research results provide a reference for clinical application of them. However, there is still a lack of large-scale multi-center clinical trials to confirm the efficacy and safety of them. The regularity of the relationship between the structures of various constituents and their corresponding functions is still unknown and the relevant signal transduction pathways and structure-activity relationship need to be further studied. This paper summarized and analyzed the determination methods of platelet functions and the research results of antiplatelet Chinese medicines, which is of reference value for the research of effective and safe antiplatelet Chinese medicines.


Assuntos
Produtos Biológicos , Medicina Tradicional do Leste Asiático , China , Inibidores da Agregação Plaquetária/farmacologia , Testes de Função Plaquetária
4.
Zhongguo Zhong Yao Za Zhi ; 45(10): 2446-2453, 2020 May.
Artigo em Zh | MEDLINE | ID: mdl-32495605

RESUMO

The aim of this paper was to explore the effect of Xueshuantong Injection(freeze-dried powder,XST) on κ-carrageenan-induced thrombosis and blood flow from the aspects of interactions among blood flow,vascular endothelium and platelets. Fifty male Sprague-Dawley rats(190-200 g) were randomized into five groups: control group, model group, heparin sodium(1 000 U·kg~(-1)) group, low-dose and high-dose(50, 150 mg·kg~(-1)) XST groups. Rats were intraperitoneally injected with corresponding drugs and normal saline(normal control and model groups) for 10 days. One hour after drugs were administered intraperitoneally on the 7 th day, each rat was injected with κ-carrageenan(Type Ⅰ, 1 mg·kg~(-1)) which was dissolved in physiological saline by intravenous administration in the tail to establish tail thrombus model. The lengths of black tails of the rats were measured at 2, 6, 24 and 48 h after modeling. Vevo®2100 small animal ultrasound imaging system was used to detect the internal diameter of rat common carotid artery, blood flow velocity and heart rate, and then the blood flow and shear rate were calculated. Meanwhile, the microcirculatory blood flow perfusion in the thigh surface and tail of rats were detected by laser speckle blood flow imaging system. Platelet aggregometry was used to detect the max platelet aggregation rate in rats. Pathological changes in tail were observed through hematoxylin-eosin staining, and Western blot was used to detect the protein content of platelet piezo1. According to the results, XST could inhibit the rat tail arterial thrombosis and significantly reduce the length of black tail(P<0.05). The blood flow of common carotid artery in XST low dose group was significantly higher than that in the model group(P<0.05). XST high dose group could significantly increase the microcirculatory blood flow perfusion of the tail in rats as compared with the model group(P<0.05). XST high dose group could significantly inhibit platelet aggregation rate(P<0.05) and XST low dose group could significantly inhibit platelet piezo1 protein expression(P<0.01). In summary, XST could play an effect in fighting against thrombosis induced by κ-carrageenan in rats, which may be related to significantly inhibiting platelet aggregation, improving body's blood flow state, maintaining normal hemodynamic environment and affecting mechanical ion channel protein piezo1.


Assuntos
Medicamentos de Ervas Chinesas , Trombose , Animais , Masculino , Microcirculação , Ratos , Ratos Sprague-Dawley
5.
Expert Rev Mol Med ; 20: e4, 2018 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-29747718

RESUMO

The field of Traditional Chinese Medicine (TCM) represents a vast and largely untapped resource for modern medicine. Exemplified by the success of the antimalarial artemisinin, the recent years have seen a rapid increase in the understanding and application of TCM-derived herbs and formulations for evidence-based therapy. In this review, we summarise and discuss the developmental history, clinical background and molecular basis of an action for several representative TCM-derived medicines, including artemisinin, arsenic trioxide, berberine and Salvia miltiorrhiza or Danshen. Through this, we highlight important examples of how TCM-derived medicines have already contributed to modern medicine, and discuss potential avenues for further research.


Assuntos
Medicina Tradicional Chinesa/história , História do Século XVII , História do Século XVIII , História do Século XIX , História do Século XX , História do Século XXI , Humanos
6.
Zhongguo Zhong Yao Za Zhi ; 43(3): 452-456, 2018 Feb.
Artigo em Zh | MEDLINE | ID: mdl-29600607

RESUMO

On the basis of chemical content determination, the bioassay methods can be used to comprehensively evaluate and control the Chinese medicine compound. This paper analyzed the newly published literature on traditional Chinese medicine(TCM) bioassay. The selection of standard control substances and the establishment of experimental system are the main difficulties in bioassay. At present, the standard control substances mainly include: different sources of products with basically similar components, certified medicinal materials, genuine medicinal materials, commonly used chemical drugs or biological products with similar pharmacological functions, as well as Chinese medicine potency conversed by activity of biological products. In this paper, the common bioassays would be summarized from the clinical efficacy of activating blood circulation and removing stasis and clearing heat and detoxification. It is one of the important contents in the industrial production of traditional Chinese medicine to gradually establish the bioassay platform of Chinese medicine from the enterprise's internal control to the industry. recognition.


Assuntos
Bioensaio , Medicamentos de Ervas Chinesas/normas , Medicina Tradicional Chinesa , Controle de Qualidade
7.
Zhongguo Zhong Yao Za Zhi ; 42(2): 341-346, 2017 Jan.
Artigo em Zh | MEDLINE | ID: mdl-28948741

RESUMO

To investigate the anti-platelet adhesive effect and possible mechanisms of Xueshuantong capsule (XST) under flow conditions. Human umbilical vein endothelial cells (HUVECs) and human platelets were employed as experimental materials, and TNF-α (20 µg•L⁻¹) was used to establish vascular endothelial cell injury models. In vivo flow conditions were simulated under controlled shear stress of 0.1 Pa and 0.9 Pa by Bioflux1000 assays accordingly. Anti-platelet adhesive effects of XST at 0.3 g•L⁻¹ were dynamically monitored by microscopic time-lapse photography. Western blotting was employed to detect the VCAM-1 expression on endothelial cells, and the release of 6-keto-PGF1α and TXB2 was tested by radioimmunoassay. The results showed that XST could inhibit the platelets adhesion under both physiological and pathological flow conditions, and the inhibition rate was 15.0% and 34.1% respectively. Under pathological low shear stress or static conditions, XST could significantly inhibit endothelial cells VCAM-1 expression and TXB2 release (P<0.05). These results suggested that XST inhibited platelets adhering to injured endothelium via decreasing VCAM-1 expression and TXA2 secretion from endothelium. From the interactions among blood flow, vascular endothelium and platelets, the anti-thrombosis effects of XST were possibly related to endothelial cells protection and therefore inhibiting platelets adhesion. Under different flow conditions, the antiplatelet adhesion effect of XST was different, and the pathological low shear stress was more conducive to the efficacy of XST.


Assuntos
Plaquetas/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Fibrinolíticos/farmacologia , Adesividade Plaquetária/efeitos dos fármacos , Cápsulas , Adesão Celular , Células Cultivadas , Endotélio Vascular , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos
8.
Small ; 12(34): 4675-81, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27295361

RESUMO

Porous matrix stiffness modulates response to targeted therapy. Poroelastic behavior within porous matrix may modulate the molecule events in cell-matrix and cell-cell interaction like the complex formation of human epidermal growth factor receptor-2 (HER2)-Src-α6ß4 integrin, influencing the targeted therapy with lapatinib.


Assuntos
Neoplasias da Mama/terapia , Matriz Extracelular/metabolismo , Terapia de Alvo Molecular , Resinas Acrílicas/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Integrina beta4/metabolismo , Lapatinib , Porosidade , Quinazolinas/farmacologia , Quinazolinas/uso terapêutico , Receptor ErbB-2
9.
BMC Complement Altern Med ; 15: 109, 2015 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-25886942

RESUMO

BACKGROUND: Yindan Xinnaotong capsule has been used for treating cardio-cerebrovascular diseases for several decades in China. Exercise training can protect against the development of atherosclerosis. The aim of the present study is to evaluate the joint effect of YXC and exercise on atherosclerosis in rats. METHODS: A combined method involving low shear stress and a high-fat diet was used to establish the atherosclerosis model in rats. Partial ligation of the left common carotid artery was performed, and then the rats were divided into 9 treatment groups according to a 3 × 3 factorial design with two factors and three levels for each factor, swimming of 0, 0.5, 1 h daily and YXC administration of 0, 1, 2 g/kg p.o. daily. Next the interventions of swimming and YXC were executed for 8 weeks. After that, blood samples were collected to determine blood viscosity, plasma viscosity, haematocrit (HCT), fibrinogen (FIB), blood lipid profile (including total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), triglyceride (TG) and high-density lipoprotein-cholesterol (HDL-C)), nitric oxide (NO), 6-keto- prostaglandin (PG) F1α, endothelin (ET) and thromboxane (TX) B2. The common carotid arteries of the rats were harvested to examine pathological changes, wall thickness and circumference, and the expression of SM22αwas assayed via immune-histochemistry. RESULTS: The early pathological changes were observed. The joint effects of YXC and swimming showed significant changes in the examined parameters: (1) decreases in plasma viscosity, blood viscosity and FIB; (2) increases in NO and 6-keto-PGF1α; (3) decreases in ET and TXB2; and (4) decreases in LDL-C and TG. The combination of 2 g/kg YXC and 1 h of swimming led to synergistic decreases in LDL-C and TG. The interactive effect between YXC and swimming was obvious in decreasing wall thickness. Swimming alone was able to up-regulate the expression of SM22α. CONCLUSIONS: In conclusion, this study indicates that the combination of YXC and swimming may prevent atherosclerosis through a synergistic effect between YXC and swimming in improving blood circulation, hemorheological parameters, blood lipids levels and the vascular endothelium in rats. The vascular remodeling may be contributed to the prevention effects on AS by up-regulating SM22α.


Assuntos
Aterosclerose/prevenção & controle , Medicamentos de Ervas Chinesas/uso terapêutico , Lipídeos/sangue , Condicionamento Físico Animal/fisiologia , Fitoterapia , Natação/fisiologia , 6-Cetoprostaglandina F1 alfa/sangue , Animais , Aterosclerose/sangue , Aterosclerose/etiologia , Aterosclerose/metabolismo , Circulação Sanguínea/efeitos dos fármacos , Cápsulas , China , Colesterol/sangue , Dieta Hiperlipídica , Medicamentos de Ervas Chinesas/farmacologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Fibrinogênio/metabolismo , Masculino , Proteínas dos Microfilamentos/metabolismo , Proteínas Musculares/metabolismo , Óxido Nítrico/sangue , Ratos Sprague-Dawley , Tromboxano B2/sangue , Triglicerídeos/sangue
10.
Zhongguo Zhong Yao Za Zhi ; 40(23): 4597-602, 2015 Dec.
Artigo em Zh | MEDLINE | ID: mdl-27141669

RESUMO

A in vitro platelet aggregation bioassay was developed for the quality control of XST capsules. The in vitro anti-platelet aggregation effect in rats was observed to detect the bioactivity of XST capsules. Panax notoginseng saponins and Xuesaitong lyophilizedpowder for injection were taken as standard control substances to determine the potency. According to the results, XST capsules showeda significant inhibitory effect on thrombin-induced platelet aggregation in a dose-dependent manner. The in vitro anti-platelet activity oflyophilized powder for injection was stabler than that of Panax notoginseng saponins, and so suitable to serve as a standard control substance. The biological potency of XST capsules compared with standard control substance was detected by using parallel line assay. According to the results, the established bioassay method had a good repeatability (RSD 2.92%). The sample test results could pass thereliability test(linear deviation P > 0.05, parallel deviation P > 0.05). This bioassay method could be used as one of the complementary quality control methods for XST capsules.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Panax notoginseng/química , Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Animais , Cápsulas/farmacologia , Masculino , Ratos , Ratos Sprague-Dawley , Saponinas/farmacologia
11.
Small Methods ; 8(1): e2300520, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37775303

RESUMO

Active deformation behavior reflects cell structural dynamics adapting to varying environmental constraints during malignancy progression. In most cases, cell mechanics is characterized by modeling using static equilibrium systems, which fails to comprehend cell deformation behavior leading to inaccuracies in distinguishing cancer cells from normal cells. Here, a method is introduced to measure the active deformation behavior of cancer cells using atomic force microscopy (AFM) and the newly developed deformation behavior cytometry (DBC). During the measurement, cells are deformed and allows a long timescale relaxation (≈5 s). Two parameters are derived to represent deformation behavior: apparent Poisson's ratio for adherent cells, which is measured with AFM and refers to the ratio of the lateral strain to the longitudinal strain of the cell, and shape recovery for suspended cells, which is measured with DBC. Active deformation behavior defines cancer cell mechanics better than traditional mechanical parameters (e.g., stiffness, diffusion, and viscosity). Additionally, aquaporins are essential for promoting the deformation behavior, while the actin cytoskeleton acts as a downstream effector. Therefore, the potential application of the cancer cell active deformation behavior as a biomechanical marker or therapeutic target in cancer treatment should be evaluated.


Assuntos
Citoesqueleto de Actina , Neoplasias , Humanos , Microscopia de Força Atômica
12.
Zhongguo Zhong Yao Za Zhi ; 37(8): 1140-2, 2012 Apr.
Artigo em Zh | MEDLINE | ID: mdl-22779365

RESUMO

Identification of the native habitat of Chinese medicine decoction pieces plays an important role in the use of Chinese Heber medicine. However, the traditional method always based on subjective description, lack of quantitative information. In this study, nanomechanical analysis of Ophiopogonis Radix, Polygonati Odorati Rhizoma and Curcumae Aromaticae Radix coming from different districts was carried out by using the force-distance curve of atomic force microscopy (AFM), including stiffness (represented by the slope of the force curve) and adhesion work (calculated via the adhesion area of the retrace line in force-distance curve). The results showed that the Ophiopogonis Radix from Sichuan province (slope 0.03 +/- 0.001) was significantly stiffer but less sticky [adhesion work 393.98 +/- 49.21 x 10(-10)) J] in comparison with that from Hubei province [slope 0.018 +/- 0.001, adhesion work (985.67 +/- 91.61) x 10(-10) J]; the Polygonati Odorati Rhizoma Hunan province was stiffer (slope 0.03 +/- 0.002) and stickier [adhesion work (413.67 +/- 92.58) x10(-10) J] than that from Dongbei province [slope 0.019 +/- 0.002, adhesion work (27.37 +/- 11.05) x 10(-10) J]; the Curcumae Aromaticae Radix from Sichuan province was also stiffer (slope 0.019 +/- 0.0017) but less stickier [adhesion work (1179.79 +/- 225.05) x 10(-10) J] than that from Hubei province [slope 0.013 +/- 0.0006, adhesion work (2831.27 +/- 93.71) x 10(-10)]. It is indicated that changes in mechanical properties of Chinese medicine decoction pieces correlate well with their origin. This method may provide quantitative information for the identification of the native habitat of Chinese medicine decoction pieces.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicina Tradicional do Leste Asiático/métodos , Microscopia de Força Atômica/métodos , Ecossistema
13.
Front Med ; 16(1): 1-9, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35290595

RESUMO

Malaria is an ancient infectious disease that threatens millions of lives globally even today. The discovery of artemisinin, inspired by traditional Chinese medicine (TCM), has brought in a paradigm shift and been recognized as the "best hope for the treatment of malaria" by World Health Organization. With its high potency and low toxicity, the wide use of artemisinin effectively treats the otherwise drug-resistant parasites and helps many countries, including China, to eventually eradicate malaria. Here, we will first review the initial discovery of artemisinin, an extraordinary journey that was in stark contrast with many drugs in western medicine. We will then discuss how artemisinin and its derivatives could be repurposed to treat cancer, inflammation, immunoregulation-related diseases, and COVID-19. Finally, we will discuss the implications of the "artemisinin story" and how that can better guide the development of TCM today. We believe that artemisinin is just a starting point and TCM will play an even bigger role in healthcare in the 21st century.


Assuntos
Artemisininas , Tratamento Farmacológico da COVID-19 , Neoplasias , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Reposicionamento de Medicamentos , Humanos , Medicina Tradicional Chinesa , Neoplasias/tratamento farmacológico
14.
Front Pharmacol ; 13: 891889, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35873580

RESUMO

Qing-Jin-Hua-Tan-Decoction (QJHTD), a classic famous Chinese ancient prescription, has been used for treatment of pulmonary diseases since Ming Dynasty. A total of 22 prototype compounds of QJHTD absorbed into rat blood were chosen as candidates for the pharmacological network analysis and molecular docking. The targets from the intersection of compound target and ALI disease targets were used for GO and KEGG enrichment analyses. Molecular docking was adopted to further verify the interactions between 22 components and the top 20 targets with higher degree values in the component-target-pathway network. In vitro experiments were performed to verify the results of network pharmacology using SPR experiments, Western blot experiments, and the PMA-induced neutrophils to produce neutrophil extracellular trap (NET) model. The compound-target-pathway network includes 176 targets and 20 signaling pathways in which the degree of MAPK14, CDK2, EGFR, F2, SRC, and AKT1 is higher than that of other targets and which may be potential disease targets. The biological processes in QJHTD for ALI mainly included protein phosphorylation, response to wounding, response to bacterium, regulation of inflammatory response, and so on. KEGG enrichment analyses revealed multiple signaling pathways, including lipid and atherosclerosis, HIF-1 signaling pathway, renin-angiotensin system, and neutrophil extracellular trap formation. The molecular docking results showed that baicalin, oroxylin A-7-glucuronide, hispidulin-7-O-ß-D-glucuronide, wogonoside, baicalein, wogonin, tianshic acid, and mangiferin can be combined with most of the targets, which might be the core components of QJHTD in treatment of ALI. Direct binding ability of baicalein, wogonin, and baicalin to thrombin protein was all micromolar, and their KD values were 11.92 µM, 1.303 µM, and 1.146 µM, respectively, revealed by SPR experiments, and QJHTD could inhibit Src phosphorylation in LPS-activated neutrophils by Western blot experiments. The experimental results of PMA-induced neutrophils to produce NETs indicated that QJHTD could inhibit the production of NETs. This study revealed the active compounds, effective targets, and potential pharmacological mechanisms of QJHTD acting on ALI.

15.
Front Nutr ; 9: 961301, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118749

RESUMO

Water-soluble tomato concentrate (WSTC), extracted from mature tomatoes, is the first health product in Europe that has been approved "to help maintain normal platelet activity to maintain healthy blood flow." We hypothesized that WSTC might exert an influence on blood flow shear stress-induced platelet aggregation (SIPA) and in turn maintains healthy blood flow. We used a microfluidic system to measure the effects of WSTC on SIPA in vitro. We also used the strenuous exercise rat model and the κ-carrageenan-induced rat tail thrombosis model to demonstrate the effects of WSTC on blood flow. WSTC significantly inhibited platelet aggregation at pathological high shear rate of 4,000 s-1 and 8,000 s-1 in vitro (P < 0.05 or P < 0.01). WSTC reduced the platelet adhesion rate and increased the rolling speed of platelets by inhibiting binding to Von Willebrand Factor (vWF) (P < 0.05 or P < 0.01). The oral administration of WSTC for 4 weeks in strenuous exercise rats alleviated hyper-reactivity of the platelets and led to a significant reduction in the plasma levels of catecholamine and IL-6. WSTC treatment also led to a reduction in black tail length, reduced blood flow pulse index (PI) and vascular resistance index (RI), and ameliorated local microcirculation perfusion in a rat model of thrombosis. WSTC exerted obvious inhibitory effects on the platelet aggregation induced by shear flow and alleviated the blood flow and microcirculation abnormities induced by an inflammatory reaction.

16.
Cell Chem Biol ; 29(8): 1248-1259.e6, 2022 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-35858615

RESUMO

Sepsis is a systemic inflammatory response syndrome with high mortality and morbidity worldwide. In this study, we demonstrate that capsaicin not only suppresses inflammation in lipopolysaccharide (LPS)-induced macrophages, but also effectively inhibits endotoxemia or sepsis-related inflammation in vivo. We have designed and synthesized a series of capsaicin-based probes, which permit the profiling of the target proteins of capsaicin using activity-based protein profiling (ABPP). Among the identified protein targets, we discover that capsaicin directly binds to and inhibits PKM2 and LDHA, and further suppresses the Warburg effect in inflammatory macrophages. Moreover, capsaicin targets COX-2 and downregulates its expression in vivo and in vitro. Taken together, the present findings indicate that capsaicin alleviates the inflammation response and the Warburg effect in a TRPV1-independent manner by targeting PKM2-LDHA and COX-2 in sepsis. Thus, capsaicin may function as a novel agent for sepsis and inflammation treatment.


Assuntos
Capsaicina , Sepse , Capsaicina/farmacologia , Proteínas de Transporte , Ciclo-Oxigenase 2 , Humanos , Inflamação/tratamento farmacológico , L-Lactato Desidrogenase , Lipopolissacarídeos/farmacologia , Proteínas de Membrana , Sepse/tratamento farmacológico , Canais de Cátion TRPV , Hormônios Tireóideos , Proteínas de Ligação a Hormônio da Tireoide
17.
Parasitol Int ; 80: 102226, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33137498

RESUMO

Malaria remains a widespread life-threatening infectious disease, leading to an estimated 219 million cases and around 435,000 deaths. After an unprecedented success, the antimalarial progress is at a standstill. Therefore, new methods are urgently needed to decrease drug resistant and enhance antimalarial efficacy. According to the alteration of erythrocyte biomechanical properties and the immune evasion mechanism of parasites, drugs, which can improve blood circulation, can be chosen to combine with antimalarial drugs for malaria treatment. Ginkgo biloba extract (GBE), one of drug for vascular disease, was used to combine with artemisinin for Plasmodium yoelii therapy. Artemisinin-GBE combination therapy (AGCT) demonstrated remarkable antimalarial efficacy by decreasing infection rate, improving blood microcirculation and modulating immune system. Besides, the expression of invasion related genes, such as AMA1, MSP1 and Py01365, can be suppressed by AGCT, hindering invasion process of merozoites. This new antimalarial strategy, combining antimalarial drugs with drugs that improve blood circulation, may enhance the antimalarial efficacy and ameliorate restoration ability, proving a potential method for finding ideal compatible drugs to improve malaria therapy.


Assuntos
Antimaláricos/farmacologia , Artemisininas/farmacologia , Malária/prevenção & controle , Extratos Vegetais/farmacologia , Plasmodium yoelii/efeitos dos fármacos , Animais , Circulação Sanguínea/efeitos dos fármacos , Quimioterapia Combinada , Expressão Gênica/efeitos dos fármacos , Ginkgo biloba , Imunidade Inata/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C
18.
Front Pharmacol ; 12: 606245, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33841141

RESUMO

XueShuanTong (XST) comprising therapeutically active ginsenosides, a lyophilized extract of Panax notoginseng roots, is extensively used in traditional Chinese medicine to treat ischemic heart and cerebrovascular diseases. Our recent study shows that treatment with XST inhibits shear-induced thrombosis formation but the underlying mechanism remained unclear. This study aimed to investigate the hypothesis that XST inhibited shear-induced platelet aggregation via targeting the mechanosensitive Ca2+-permeable Piezo1 channel by performing platelet aggregation assay, Ca2+ imaging and Western blotting analysis. Exposure to shear at physiologically (1,000-2000 s-1) and pathologically related rates (4,000-6,000 s-1) induced platelet aggregation that was inhibited by treatment with GsMTx-4. Exposure to shear evoked robust Ca2+ responses in platelets that were inhibited by treatment with GsMTx-4 and conversely enhanced by treatment with Yoda1. Treatment with XST at a clinically relevant concentration (0.15 g L-1) potently inhibited shear-induced Ca2+ responses and platelet aggregation, without altering vWF-mediated platelet adhesion and rolling. Exposure to shear, while resulting in no effect on the calpain-2 expression in platelets, induced calpain-2-mediated cleavage of talin1 protein, which is known to be critical for platelet activation. Shear-induced activation of calpain-2 and cleavage of talin1 were attenuated by treatment with XST. Taken together, our results suggest that XST inhibits shear-induced platelet aggregation via targeting the Piezo1 channel to prevent Piezo1-mediated Ca2+ signaling and downstream calpain-2 and talin1 signal pathway, thus providing novel insights into the mechanism of the therapeutic action of XST on platelet aggregation and thrombosis formation.

19.
Artigo em Inglês | MEDLINE | ID: mdl-20831352

RESUMO

Viscosity of blood substitutes is among the important determinants to restore microcirculation. Sodium alginate (SA) is always mentioned as "viscosity modifier" in creating blood substitutes. In the present study, the whole blood was diluted using SA solutions to final hematocrits of 10%, 20%, and 35%, respectively. The whole blood viscosity (WBV) at different shear rates, plasma viscosity (PV), and rheological behavior of red blood cells (RBCs) was studied in vitro. The results show that SA may induce RBCs aggregation in a dose-dependent manner. Furthermore, the effect of SA on RBCs aggregation maybe involve the regulation of microcirculation.


Assuntos
Alginatos/farmacologia , Viscosidade Sanguínea/efeitos dos fármacos , Agregação Eritrocítica/efeitos dos fármacos , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Adulto , Deformação Eritrocítica/efeitos dos fármacos , Ácido Glucurônico/farmacologia , Hematócrito , Ácidos Hexurônicos/farmacologia , Humanos , Suspensões
20.
Pharmacol Ther ; 216: 107658, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32777330

RESUMO

As the first-line antimalarial drugs, artemisinins gained wide acceptance after the emergence of resistance to chloroquine in the 1950s. Artemisinin-based drugs have saved lives, especially in developing countries. The discovery of artemisinin was unique, timely, and fascinating, and the benefits of artemisinin were with far-reaching implications. Herein, we will give a brief description of various aspects of the development of artemisinin and discuss the position and perspectives of artemisinin-based drugs.


Assuntos
Antimaláricos/uso terapêutico , Artemisia annua , Artemisininas/uso terapêutico , Malária/tratamento farmacológico , Plasmodium/efeitos dos fármacos , Animais , Antimaláricos/química , Antimaláricos/isolamento & purificação , Artemisia annua/química , Artemisininas/química , Artemisininas/isolamento & purificação , Humanos , Malária/parasitologia , Estrutura Molecular , Plasmodium/patogenicidade , Relação Estrutura-Atividade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA