RESUMO
Parkinson's disease (PD) is a progressive neurodegenerative disease with a high clinical heterogeneity. According to its motor symptoms, PD patients are divided into predominant tremor-dominant, postural instability and gait difficulty-dominant/akinetic-rigid and mixed subtypes. Different subtypes show different prognostic characteristics and different sensitivities to drugs. Therefore, the early classification of PD is of great significance for the treatment and prognosis of the disease. This paper reviews the clinical classification methods of different subtypes of PD, summarizes the latest biochemical markers and imaging features, and analyzed the differences in incidence, prognosis and pathological mechanism. The current clinical treatment drugs and methods have been preliminarily targeted for treatment based on PD classification, and there are many animal models of PD subtypes have been studied, providing new methods and strategies for mechanism research and preclinical pharmacodynamics evaluation of PD subtypes.
RESUMO
This study investigated the effect of puerarin on human umbilical vein endothelial cells (HUVEC) injured with hydrogen peroxide (H2O2). HUVEC were divided into three groups: a control group, a model group (H2O2 400 μmol·L-1) and a puerarin-treated group (3, 10, 30 and 100 μmol·L-1). HUVEC were cultured with varied concentration of puerarin for 2 h and treated with H2O2 for another 24 h. Cell proliferation was detected by a CCK-8 assay. The mitochondrial membrane potential was measured by a JC-1 fluorescent probe. A transwell chamber assay was adopted to observe cell migration ability. Mitochondrial respiratory function was measured in a two-chamber titration injection respirometer (Oxygraph-2k). The expression of interleukin-1β (IL-1β), interleukin-18 (IL-18) and tumor necrosis factor-α (TNF-α) was detected by quantitative real-time PCR. The expression of pyroptosis-mediated proteins, including cleaved-cysteinyl aspartate-specific proteinase-1 (caspase-1), N-gasdermin D (N-GSDMD), NOD-like receptor protein 3 (NLRP3) and purinergic ligand-gated ion channel 7 receptor (P2X7R) was detected by Western blot. The results show that 400 μmol·L-1 H2O2 treatment for 24 h causes obvious damage to HUVEC. Compared with the model group, puerarin protected against cellular injury in a dose-dependent manner, with the greatest effect at a dose of 30 and 100 μmol·L-1. Puerarin significantly decreased the mitochondrial membrane potential and improved mitochondrial function. Puerarin inhibited cell migration induced by H2O2, suppressed the expression of IL-1β, IL-18 and TNF-α, and down-regulated the pyroptosis-mediated protein. These changes are statistically significant (P < 0.05). These findings demonstrate that puerarin has a protective effect against H2O2-induced oxidative damage of HUVEC by inhibiting the migration of HUVEC cells. The mechanism may be related to improved mitochondrial respiratory function and inhibition of pyroptosis.
RESUMO
Ischemic heart disease (IHD), which has been considered to be exclusively caused by stenosis or occlusion of coronary artery, is a significant cause of morbidity and mortality worldwide. Mitochondrial dysfunction is the main pathological basis of ischemic heart disease and reperfusion injury, and moderate mitochondrial autophagy can selectively remove damage proteins and organelles to maintain intracellular homeostasis, so mitochondrial autophagy is important for maintaining the homeostasis of cardiomyocytes. Natural drugs from plants are widely used in ischemic heart disease. In recent years, more and more natural drugs have been proven to alleviate myocardial cell damage after ischemia/reperfusion through mitochondrial autophagy. This paper reviews the research progress of natural drugs from plants medicines regulating mitochondrial autophagy in the treatment of ischemia heart disease.
RESUMO
This study was to investigate the protective effects of puerarin on myocardial ischemia/reperfusion (MI/R) injury and the underlying mechanism. The MI/R-model was established by ligating the left anterior descending artery (LAD) for 60 min followed by 24 h reperfusion, puerarin (10, 30, and 100 mg·kg-1) was orally administered 20 min before reperfusion. Cardiac function, myocardial infarct index, cardiac damage markers, inflammatory cytokines, and apoptosis index were measured to evaluate the protective effects of puerarin on MI/R injury. The activation of Nod-like receptor protein 3 (NLRP3) inflammasome and Toll like receptor 4 (TLR4)/myeloid differentiation factor 88 (Myd88)/nuclear factor kappa B (NF-κB) pathway were determined by Western blot. All animal experimental procedures were approved by the ethics committee of the Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences. The results showed that puerarin could significantly improve cardiac function, reduce myocardial infarct size, decease the levels of lactic dehydrogenase (LDH), aspartate transaminase (AST), creatine kinase-MB (CK-MB), and cardiac troponin T (cTnT) and suppress cardiomyocyte apoptosis. Meanwhile, puerarin could notably decrease the levels of inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Western blot analysis revealed that puerarin could downregulate the expression of TLR4, Myd88, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), cleaved-caspase 1, cleaved-gasdermin-D (GSDMD), IL-1β, and IL-18, as well as the phosphorylation levels of inhibitor of NF-κB α (IκBα), IκB kinase β (IKKβ), and NF-κB. These findings demonstrated that puerarin could alleviate MI/R injury by suppressing NLRP3 inflammasome activation, possibly via TLR4/Myd88/NF-κB pathway.
RESUMO
In the treatment of hypertensive crisis, the novel Rho kinase inhibitor DL0805-2 can rapidly lower systematic blood pressure, reduce pulmonary artery pressure, and has a significant protective effect on lung injury. This experiment intends to evaluate the efficacy of DL0805-2 against pulmonary arterial hypertension (PAH) and preliminarily reveals its underlying mechanism. Animal welfare and experimental procedures are in accordance with the provision of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. Sprague Dawley (SD) rats were randomly divided into DL0805-2 low, medium, and high dose groups (1, 3, and 10 mg·kg-1), bosentan positive control group, model group, and blank control group. The drug was administered daily on the 7th day after model establishment by monocrotaline injection. On the 25th day of the experiment, relevant indicators were examined to observe the therapeutic effect of DL0805-2 on pulmonary hypertension. DL0805-2 significantly relieved the abnormal changes in the physiological parameters related to PAH induced by monocrotaline, including reducing right ventricular systolic pressure, alleviating cardiac damage caused by pressure overload, and reducing the levels of endothelin-1 and inflammatory factors in lung tissues. DL0805-2 also attenuated pulmonary arteries remodeling. It was preliminarily discovered that DL0805-2 exerts preventive and therapeutic effect on PAH through Rho-kinase pathway. Our results suggested that DL0805-2 had good therapeutic effects on monocrotaline-induced PAH rat model. It intervened early in the disease process, effectively prevented the development of the disease, and reduced the mortality of the diseased animals. The mechanism is related to Rho-kinase pathway.
RESUMO
Salvianolic acids are the main water-soluble active compounds of Salvia miltiorrhiza and have been widely used for the treatment of cardiovascular diseases. Based on the latest studies in China and abroad, we summarize the pharmacological effects and mechanism of salvianolic acids on ischemic heart disease by describing how salvianolic acid A and salvianolic acid B protect the vascular endothelium, relax coronary arteries, promote angiogenesis and anti-platelet aggregation, inhibit the inflammatory response, anti-cell apoptosis, and scavenge free radicals. This review provides a theoretical basis for further research on the effects of salvianolic acids on ischemic heart disease and their potential for drug development.
RESUMO
Flavonoids are a large class of bioactive compounds widely found in food and plants. Studies have found that they have a good preventive and therapeutic effect on cardiovascular diseases. Flavonoids have a wide range of pharmacological effects, including antioxidation, anti-inflammation, vasodila-tion, inhibiting platelet aggregation and regulating blood lipids and so on. The cardiovascular protective mechanism of fla-vonoids involves the enzymes that inhibit the production of oxy-gen derived free radicals, inhibition of lipid peroxidation and in-flammatory factor, down-regulation of epoxy synthase activity and activation of AMPK and nuclear factor kappa B signaling pathway. In this review we summarize the so far acquired knowl-edge of the most important mechanisms of flavonoid action, so as to provide the theoretical basis for the research and development of the active monomers in flavonoid and compound preparations.
RESUMO
OBJECTIVE To investigate the pharmacological effect and mechanism of Salvianolic acid A (SAA) on pulmonary vascular remodeling. METHODS In current study, we conducted a series of experiments to clarify the effect of SAA,a kind of polyphenol compound,in the process of EndMT in human pulmonary arterial endothelial cells and in vivo therapeutic efficacy on vascular remodeling in monocrotaline (MCT)-induced EndMT. EndMT was also induced by TGF-β1in human pulmonary arterial endothelial cells(HPAECs) in vitro.RESULTS SAA significantly attenuated EndMT,simul-taneously inhibited cell migration and reactive oxygen species(ROS)formation.In MCT-induced pulmonary arterial hypertension(PAH)model,SAA improved vascular function,decreased TGF-β1level and inhib-ited inflammation. Mechanistically, SAA stimulated Nrf2 translocation and subsequent heme oxygen-ase-1(HO-1)up-regulation.The effect of SAA on EndMT in vitro was abolished by ZnPP,a HO-1 inhibitor. CONCLUSION This study indicates a deleterious impact of oxidative stress on EndMT. Polyphenol antioxidant treatment may provide an adjunctive action to alleviate pulmonary vascular remodeling via inhibiting EndMT.
RESUMO
OBJECTIVE Salvianolic acid A (SAA) is one of the most bioactive compounds from a traditional Chinese medicine called Dan Shen(Salvia Miltiorrhiza Bunge)and exhibits many pharmaco-logical activities.Previous studies have indicated that SAA may inhibit endothelial dysfunction and vascular remodeling in spontaneously hypertensive rats. However, whether SAA improves vascular remodeling induced by pulmonary arterial hypertension (PAH) remains unknown. In this study we examined whether SAA attenuated vascular remodeling in a PAH rat induced by monocrotaline(MCT),and elucidated the underlying mechanisms.METHODS PAH was induced in rats by injecting a single dose of monocrotaline (MCT 60 mg·kg-1).The rats were orally treated with either SAA(0.3,1,3 mg·kg-1·d-1)or a positive con-trol Bosentan(30 mg·kg-1·d-1)for 4 weeks.Echocardiography and hemodynamic measurements were performed on d 28.Then the hearts and lungs were harvested,the organ indices and pulmonary artery wall thickness were calculated,and biochemical and histochemical analysis were conducted.The levels of apoptotic and signaling proteins in the lungs were measured using immunoblotting.RESULTS Treatment with SAA effectively ameliorated MCT-induced pulmonary artery remodeling,pulmonary hemodynamic ab-normalities and the subsequent increases of right ventricular systolic pressure (RVSP). Furthermore, the treatments significantly attenuated MCT-induced hypertrophic damage of myocardium,parenchymal in-jury and collagen deposition in the lungs.Moreover,the treatments attenuated MCT-induced apoptosis and fibrosis in the lungs.The treatments partially restored MCT-induced reductions of bone morphoge-netic protein typeⅡ receptor (BMPRⅡ) and phosphorylated Smad1/5 in the lungs. CONCLUSION SAA ameliorates the pulmonary arterial remodeling in MCT-induced PAH rats most likely via activating the BMPRII-Smad pathway and inhibiting apoptosis.Thus,SAA may have therapeutic potential for the pa-tients at high risk of PAH.
RESUMO
Flavonoids are a large family of bioactive compounds widely found in foods and plants. Mang studies have proven the preventive and therapeutic effects of flavonoids in cardiovascular disease.Flavonoids has a wide range of pharmacological effects,including antioxidant,anti-inflammatory,vaso-dilation,avoiding the thrombus formation,improving endothelial function,modifying lipid levels and regulating blood lipids through different mechanisms of action.The cardiovascular protective mechanism of flavo-noids are the enzymes that inhibit the production of oxygen derived free radicals,inhibition of lipid peroxida-tion and inflammatory factor, down-regulation of epoxy synthase activity and the activation of AMPK and nuclear factor kappa B signaling pathway. In this review article we review and summarize the so far acquired knowledge of the most important mechanisms of action of flavonoids,to provide theoretical basis for the research and development of the active monomers in flavonoid and compound preparations.
RESUMO
OBJECTIVE To investigate the effects of total flavonoids of bugloss(TFB)on left ventricular (LV)remodeling after myocardial infarction(MI),LV size and function was compared in mice subjected to left anterior descending coronary artery ligation. METHODS 28 d after MI, the infarcted fraction of the LV and LV mass, systolic and diastolic function were measured. Capillary density and myocyte width in the nonischemic portion of the LV were also determined.RESULTS 28 d after MI,both groups had dilated LVs with decreased fractional shortening and lower ejection fractions. Although the infarcted size of the LV was similar in both groups,LV end-diastolic internal diameter,end-diastolic volume,and mass were lower, but fractional shortening, ejection fraction, and the maximum rate of developed LV pressure(dp/dtmax)were greater in TFB treated mice than in control mice.Impairment of diastolic func-tion, as measured by the time constant of isovolumic relaxation (t) and the maximum rate of LV pres-sure decay(dp/dtmin),was more marked in control mice than in TFB treated mice.Mortality after MI was greater in control mice than in TFB treated mice.In control mice,capillary density and myocyte width in the nonischemic portion of the LV did not differ before and 28 days after MI, whereas in TFB treated mice, capillary density increased and myocyte width declined after MI. CONCLUSION These results suggest that the presence of TFB limits LV dysfunction and remodeling in a murine model of MI in part by decreasing myocyte hypertrophy in the remote myocardium.
RESUMO
Curcumin is the principal curcuminoid of the rhizomes of Curcuma longa(turmeric,Jiang Huang), which has more than 6000 years of application history in India and other Asian countries. At present,curcumin is sold as an herbal supplement,cosmetics ingredient,food flavoring,and food coloring. In China curcumin is mainly used in food, while in western countries it has been regarded as a health care product and is contained in the British Pharmacopoeia (2017), United States Pharmacopeia (40) and European Pharmacopoeia (8.7th ed.). Curcumin has been proved to have multiple pharmacology effects including anti-fibrosis, anti-tumor, anti-inflammation effects and so on. As its broad biological activities, it is applicated in a lot of diseases such as hyperlipidemia, infection and cancer. Among them, the anti-cancer effect of curcumin is the most attractive. In the treatment of cancer and related diseases, curcumin has been tested in phase I and II clinical trials in several research centers across the world and has been approved by the U.S.FDA into the phase III clinical trial.It has been listed as the third generation of cancer chemoprevention agent by the U.S.National Cancer Institute.Curcumin has been proved to inhibit the proliferation of a variety of tumor cells through regulating a variety of tran-scription factors(NF-κB,AP-1,etc),mitogen-activated protein kinase(MAPK),growth factor receptor ki-nase(PDGFR,VEGFR,etc)and cyclooxygenase.It plays an important role in the cell cycle and further to inhibit proliferation.Curcumin can also inhibit the migration of tumor cells by activating caspase and in-ducing tumor cell apoptosis.However,curcumin still needs researches to confirm its effects and mecha-nisms and find its exact indications. There is still a long way to go to make curcumin better applied in clinical practice in the further.
RESUMO
Objective To investigate the application of the fluorescein diacetate (FDA) microplate assay in cell viability detection. Methods Cells were seeded in a 96-well culture plate until detection. After incubated with FDA,the plate was detected by fluorescence microplate analyzer. The effects of FDA incubation duration,concentration,and other factors on the assay's accuracy and stability were assessed. We also compared the results of FDA with methyl thiazolyl(MTT) in terms of cell numbers and HOinjury. Results Within 0-30 minutes,the fluorescence-cell number coefficient of FDA assay increased with duration and reached 0.99 in 27-30 minutes. The optimum concentration of final FDA in this study was 10-30 μg/ml. On cell viability detection,the result of FDA method was equivalent to MTT method. As to HOinjury assay,the sensitivity of FDA method was superior to MTT on the higher concentration HOtreatment due to a relative shorter duration for detection. Conclusion As a stable and reliable method,FDA is feasible for cell variability detection under varied conditions.
Assuntos
Humanos , Bioensaio , Sobrevivência Celular , Fluoresceínas , Química , Fluorescência , Peróxido de Hidrogênio , Coloração e RotulagemRESUMO
Eucommia ulmoides is a valuable traditional Chinese medicine, whose cortexes have long been used as medi cines. Due to the scarcity of its resources, people began using its leaves instead of cortexes in medicines. Eucommiae Folium and its leaves have many pharmacological effects and thereby being clinically applied as genuine traditional Chinese medicines. Modern pharmological studies have showed that Eucommiae Folium leaves have such effects as blood pressure reduction, blood lipid regulation, cardiovascular protection, anti-obesity, anti-inflammation, anti-virus, enhancement of immunologic function, resistance against senility and anti-fatigue. In clinic, Eucommiae Folium is mainly used to treat hypertention and obstetrical and gynecological disease. The essay summarizes the latest advance in domestic and foreign studie on pharmacological effeets and clinical applications of Eucommiae Folium leaves, and thus providing reference for studies on new drugs of Eucommiae Folium leave.
Assuntos
Animais , Humanos , Química Farmacêutica , Medicamentos de Ervas Chinesas , Química , Farmacologia , Usos Terapêuticos , Eucommiaceae , QuímicaRESUMO
AIM@#To investigate the relationship between cerebroprotection of pinocembrin and epoxyeicosatrienoic acids (EETs) and their regulating enzyme soluble epoxide hydrolase (sEH).@*METHODS@#Rats underwent middle cerebral artery occlusion (MCAO) to mimic permanent focal ischemia, and pinocembrin was administrated via tail vein injection at 10 min, 4 h, 8 h and 23 h after MCAO. After 24 MCAO, rats were re-anesthetized, and the blood and brain were harvested and analyzed.@*RESULTS@#Pinocembrin displayed significant protective effects on MCAO rats indicated by reduced neurological deficits and infarct volume. Importantly, co-administration of 0.2 mg·kg(-1) 14, 15-EEZE, a putative selective EET antagonist, weakened the beneficial effects of pinocembrin. 14, 15-EET levels in the blood and brain of rats after 24 h MCAO were elevated in the presence of pinocembrin. In an assay for hydrolase activity, pinocembrin significantly lowered brain sEH activity of MCAO rats and inhibited recombinant human sEH activity in a concentration-dependent manner (IC50, 2.58 μmol·L(-1)). In addition, Western blot and immunohistochemistry analysis showed that pinocembrin at doses of 10 mg·kg(-1) and 30 mg·kg(-1) significantly down-regulated sEH protein in rat brain, especially the hippocampus CA1 region of MCAO rats.@*CONCLUSION@#Inhibiting sEH and then increasing the potency of EETs may be one of the mechanisms through which pinocembrin provides cerebral protection.
Assuntos
Animais , Humanos , Masculino , Ratos , Ácidos Araquidônicos , Metabolismo , Encéfalo , Metabolismo , Isquemia Encefálica , Tratamento Farmacológico , Genética , Metabolismo , Modelos Animais de Doenças , Epóxido Hidrolases , Genética , Metabolismo , Flavanonas , Substâncias Protetoras , Ratos Sprague-DawleyRESUMO
Myocardial ischemic preconditioning and postconditioning can reduce myocardial infarct size, improve myocardial contractility, protect coronary endothelial and myocardial cell ultrastructure, as well as reduce the incidence of arrhythmias. Clinical practice has confirmed the safety and efficacy of these two methods of myocardial protection. This paper reviewed about ischemic preconditioning and postconditioning protection mechanisms in myocardial ischemia reperfusion injury and clinical research literatures in recent years, to provide a theoretical basis for finding new treatment strategies on the prevention and treatment of ischemic cardiomyopathy.
Assuntos
Animais , Humanos , Pós-Condicionamento Isquêmico , Métodos , Precondicionamento Isquêmico Miocárdico , Métodos , Infarto do Miocárdio , Terapêutica , Isquemia Miocárdica , Terapêutica , Reperfusão Miocárdica , Traumatismo por Reperfusão Miocárdica , Receptores Acoplados a Proteínas G , Transdução de SinaisRESUMO
OBJECTIVE: To investigate the inhibitory effects of different solvent extracts from Guizhi Fuling on the proliferation in human cervical carcinoma cells and its possible mechanisms. METHODS: MTT assay was used to detect the proliferation in the HeLa and C33A human cervical carcinoma cells, and the enzyme-linked immunosorbent assay was used detect for the protein tyrosine kinases (PTKs) activity in vitro, and 1, 1-diphenyl-2-picrylhydrazyl (DPPH) scavenging ratio displayed antioxidant activity of different extracts from Guizhi Fuling. RESULTS: Most of different solvent extracts from Guizhi Fuling, including extracts of ethyl acetate, ethyl acetate-water, ethyl acetate-acetone, butyl alcohol-30% ethanol and butyl alcohol-50% ethanol, displayed good inhibitory activity on the proliferation in human cervical carcinoma cells. The inhibit potency to the largest for HeLa cells was butyl alcohol-30% ethanol eluate, its IC50 was (7.09±1.25) μg·mL-1, and inhibit potency to the largest for C33A cells was ethyl acetate-acetone eluate, its IC50 was (5.14±0.70) μg·mL-1. CONCLUSION: These results suggested that different solvent extracts from Guizhi Fuling, have different anticancer activity in vitro. Its mechanism may be associated with inhibition of PTKs and antioxidation activity. Copyright 2012 by the Chinese Pharmaceutical Association.
RESUMO
Cortex Fraxini is a commonly used traditional Chinese medicine. It has been indicated that Cortex Fraxini possess various pharmacological effects, including anti-pathogenic microorganism, anti-inflammatory, analgesic, anti-cancer, anti-oxidative stress, neuroprotective and vascular protect effects. Cortex Fraxini has been therapeutically used in the treatment of inflammations, bacillary dysentery, relieving fever, relieving cough and asthma. This paper reviewed recent progress in the studies on pharmacological effects and clinical applications of Cortex Fraxini.
Assuntos
Animais , Humanos , Analgésicos , Farmacologia , Toxicidade , Antibacterianos , Farmacologia , Toxicidade , Anti-Inflamatórios , Farmacologia , Toxicidade , Antineoplásicos , Farmacologia , Toxicidade , Medicamentos de Ervas Chinesas , Farmacologia , ToxicidadeRESUMO
Paxillin is a regulatory component of the complex of cytoskeletal proteins that link the actin cytoskeleton to the plasma membrane. However, the role of paxillin during smooth muscle contraction is unclear. We investigated a possible role for the membrane-associated dense plaque protein paxillin in the regulation of contraction in rat aortic vascular smooth muscle. The tyrosine phosphorylation of paxillin, which was increased by norepinephrine, reached a peak level after 1 min stimulation and then decreased with time. However, norepinephrine induced a sustained contraction that reached a steady state 30 min after application. Pretreatment with tyrphostin, an inhibitor of tyrosine kinase, inhibited the tyrosine phosphorylation of paxillin and also the contraction stimulated by norepinephrine. Both inhibitions were concentration-dependent, and the degree of correlation between them was high. These results show that, in rat aortic smooth muscle, tyrosine kinase(s) activated by norepinephrine may phosphorylate the tyrosine residues of paxillin, thereby providing a source of regulation during vascular smooth muscle contraction.