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1.
Puerariae flos has been used for oriental herbal medicine; however, its angiogenic effect has not been elucidated. We found that the extract from Puerariae flos (PFE) increased in vitro angiogenic events, such as endothelial cell proliferation, migration, and tube formation, as well as in vivo neovascularization. These events were followed by the activation of multiple signal modulators, such as extracellular signal‐regulated kinase (ERK), Akt, endothelial nitric oxide synthase (eNOS), nitric oxide production, p38, Src, and focal adhesion kinase (FAK), without increasing vascular endothelial growth factor (VEGF) expression. Inhibition of ERK, Akt, and eNOS suppressed PFE‐induced angiogenic events, and inhibition of p38 and Src activities blocked PFE‐induced endothelial cell migration. PFE did not affect the expression of intracellular adhesion molecule‐1 and vascular cell adhesion molecule‐1 and transendothelial permeability, which are involved in the adverse effects of the well‐known angiogenic inducer VEGF. These results suggest that PFE directly stimulates angiogenesis through the activation of MEK/ERK‐, phosphatidylinositol 3‐kinase/Akt/eNOS‐, and Src/FAK‐dependent pathways, without altering VEGF expression, vascular inflammation, and permeability in vitro and in vivo and may be used as a therapeutic agent for ischemic disease and tissue regeneration. Copyright © 2009 John Wiley & Sons, Ltd.  相似文献   

2.

Aim of the study

Endothelial dysfunction is involved in stroke. Recent therapeutic options for stroke have focused on the combination therapy with a polyherbal mixture. This study was designed to provide insight into the effects of JP05, a water extract of 12 herbs, on the levels of regulators in bEnd.3 mouse brain endothelial cells.

Materials and methods

Production of endothelial nitric oxide synthase (eNOS)-mediated nitric oxide (NO), the expression of vascular endothelial growth factor (VEGF) and the phosphorylations of eNOS, phosphatidylinositol 3-kinase (PI3K)/Akt, extracellular signal-regulated protein kinase (ERK) and cAMP response element binding protein (CREB) in JP05 were assayed in bEnd.3 cells, a mouse brain endothelial line.

Results

JP05 led to increase the levels of eNOS-mediated NO generation and VEGF expression in bEnd.3 cells. JP05 induced the phosphorylation of eNOS, Akt and ERK in bEnd.3 cells. As well, JP05 blocked the inhibition of PI3K/Akt and ERK activities by LY294002 (PI3K/Akt inhibitor) and PD98059 (mitogen-activated protein kinase inhibitor), respectively. JP05 also induced the phosphorylation of CREB, which plays an important role in endothelial cell function and blood vessel development.

Conclusion

Taken together, these results indicate that JP05 can upregulate eNOS-mediated NO generation and VEGF expression through the ERK and/or PI3K/Akt activation, an upstream event of angiogenesis. JP05 with vasoprotective properties has a potential therapy for human brain diseases including stroke.  相似文献   

3.
Total aralosides of Aralia elata (Miq) Seem (TASAESs) possess multiple pharmacological activity, such as anti‐inflammation, antioxidation, and antiapoptosis. However, there is no literature reporting the antiatherosclerotic effect and mechanism of TASAES so far. The aim of this study was to investigate the antiatherosclerotic effects in high‐fat diet‐induced ApoE?/? mice and potential mechanism of TASAES in ox‐LDL‐injured endothelial cells. In vivo assay, our data demonstrated that TASAES significantly reduced the atherosclerotic plaque size and caspase‐3 expression level in aortic valve. In vitro, we found that TASAES could increase endothelial cell viability, attenuated mitochondrial membrane potential depolarization, and endothelial cells apoptosis. In addition, we found that TASAES could activate SIRT1/AMPK and Akt/eNOS signaling pathways. Importantly, EX527, SIRT1 siRNA, and LY294002, Akt siRNA, remarkably abolished the antiapoptotic effects of TASAES. In conclusion, this study demonstrated that SIRT1/AMPK and Akt/eNOS signaling pathways are involved in endothelial protection of TASAES against atherosclerotic mice, suggesting that TASAES is a candidate drug for atherosclerosis treatment.  相似文献   

4.
Badiranji Buya Keli (BBK) is a traditional Uyghur medicine derived from Dracocephalum Moldavica Herba (DMH, the aerial part of Dracocephalum moldavica L.). BBK has been widely used in treating cardiovascular and cerebrovascular diseases. Here, the quality control of BBK was established by using HPLC analysis of rosmarinic acid and tilianin. After chemical standardization, the biological effects of BBK was tested. First, BBK inhibited platelet aggregation of rabbit plasma. Second, BBK induced vasodilation in rat aortic ring, and this effect was partially mediated by nitric oxide (NO) production in endothelial cells. Third, BBK induced NO production in cultured human umbilical vein endothelial cells (HUVECs). In HUVECs, the phosphorylation of endothelial NO synthase (eNOS) was markedly increased after application of BBK. Pre‐treatment with the eNOS blocker Nω‐nitro‐l ‐arginine methyl ester hydrochloride could abolish BBK‐induced NO production and eNOS phosphorylation. Taken together, these results suggest that BBK could exert beneficial effects in cardiovascular system, which may provide parts of molecular explanation to account for its traditional usage in Uyghur medicine. Copyright © 2015 John Wiley & Sons, Ltd.  相似文献   

5.
Angiogenesis plays an important role in a wide range of physiological processes and many diseases are associated with dysregulation of angiogenesis. Radix Astragali, commonly used in traditional Chinese medicine, is a potential candidate for treating such diseases. However, the biological effects of Radix Astragali on angiogenesis and its underlying mechanisms are yet to be elucidated fully. This study describes the angiogenic effects of Radix Astragali extract (RAE) on human umbilical vein endothelial cells (HUVEC) in vitro. It was shown that RAE treatment stimulated HUVEC to proliferate. A significant increase in migration was observed in RAE‐treated HUVEC using the wound healing migration assay. In addition, a significant increase in the number of branching points was observed during endothelial cell capillary formation after RAE treatment. It was shown that RAE enhances vascular endothelial growth factor (VEGF) mRNA expression, and that a specific blocker of VEGF receptor 2 (KDR/Flk) inhibited the RAE‐induced HUVEC proliferation. In addition, a decrease in the RAE‐induced HUVEC proliferation was observed after treatment with inhibitors of phosphatidylinositol 3‐kinase (PI3K), Akt and endothelial nitric oxide synthase (eNOS). Taken together, these data suggest that RAE is a potent stimulator of angiogenesis and that its pro‐angiogenic effects involve the VEGF‐KDR/Flk and PI3K‐Akt‐eNOS pathways. Copyright © 2009 John Wiley & Sons, Ltd.  相似文献   

6.
目的: 研究罗布麻叶提取物(extracts from leaves of Apocynum venetum,ELA)的抗高血压作用及其激活磷脂酰肌醇3激酶(PI3K)和(或)蛋白激酶B(Akt)信号转导通路促进一氧化氮释放的作用。 方法: 采用双肾双夹法建立Beagle犬高血压模型,随后按血压值将Beagle犬随机分为模型组(ig,生理盐水)、马来酸依那普利组(ig,1.66 mg·kg-1)、ELA低剂量组(ig 23 mg·kg-1)、高剂量组(ig ELA 46 mg·kg-1)。受试动物在单次给予上述药物后,每隔1 h记录1次动物血压,连续8 h,观察ELA的降压作用;采用细胞培养法,观察ELA对内皮细胞(EAhy 926)一氧化氮(NO)产量和内皮型一氧化氮合酶(eNOS)活性的影响;采用Western blot法,观察ELA对eNOS,磷酸化内皮型一氧化氮合酶(p-eNOS)、磷酸化磷脂酰肌醇3激酶(p-PI3K)以及磷酸化蛋白激酶B (p-Akt)表达量的影响。 结果: 给药后,ELA高、低剂量组Beagle犬收缩压分别为(140.4±7.5),(136.2±6.8) mmHg;舒张压分别为(63.5±3.3),(72.2±4.4) mmHg;平均血压分别为(88.9±4.7),(93.3±5.2)mmHg,与给药前相比均显著降低(P<0.01);ELA可显著增加EA Hy926细胞NO的释放量(P<0.01),提高eNOS活性(P<0.01);Western blot结果表明,ELA可显著增加p-eNOS,p-PI3K以及p-Akt的表达量,与对照组相比,具有显著差异(P<0.01)。 结论: ELA具有明显的降压作用。激活血管内皮细胞内PI3K/Akt信号转导途径,从而促进eNOS磷酸化,提高eNOS活性、增加NO可能是ELA降压作用的机制之一。  相似文献   

7.
目的观察低剪切力(shear stress,SS)作用下当归补血汤对内皮祖细胞(endothelial progenitor cells,EPCs)功能的影响及调控机制。方法分离培养大鼠骨髓EPCs并鉴定,将EPCs随机分为6组:正常SS组和低SS组(M199培养液培养2 h)、辛伐他汀组(0.1μmol·L^-1的辛伐他汀培养2 h)、当归补血汤高、中、低浓度组(分别予以3.2 g·L^-1,1.6 g·L^-1,0.8g·L^-1的当归补血汤培养2 h),培养结束后弃上清,正常SS组加载1.2 Pa的正常SS,余各组加载0.12 Pa的低SS,分别在第30、60、360 min检测EPCs的增殖、迁移和成小管功能、一氧化氮(nitric oxide,NO)分泌、一氧化氮合酶(endothelial nitric oxide synthase,eNOS)mRNA及蛋白激酶B(protein kinase B,Akt)的表达。结果与正常SS组比较,低SS组EPCs功能随时间延长而受损,细胞分泌NO及表达eNOS mRNA、Akt蛋白在60min时迅速上调(P<0.01),随后在360 min时显著降低;与低SS组比较,辛伐他汀和当归补血汤高、中浓度可促进360 min时的细胞功能和NO分泌,上调eNOS mRNA及Akt蛋白的表达(P<0.05)。结论当归补血汤可通过调节NO/eNOS/Akt通路来保护低SS作用下受损的EPCs功能。  相似文献   

8.
Morinda citrifolia (Noni) is extensively used in herbal remedies to prevent and treat various diseases, including hypertension. The purpose of this study was to investigate the vascular effects of noni fruit juice and characterize the upstream signaling pathways. We measured the systolic blood pressure, diastolic blood pressure, 24‐hr urinary nitric oxide (NO) metabolite excretion, bodyweight (BW), and urine examination in SHR.Cg‐Leprcp/NDmcr (SHR/cp) rats after 6 weeks noni juice (15 ml/kg) treatment. Noni juice significantly decreased blood pressure and 24‐hr urinary NO metabolite without change of BW or urine volume. Furthermore, the noni juice extract (NJE) promoted endothelial vasorelaxation in rat aorta rings and NO product through an increase in phosphorylation of endothelial nitric oxide synthase (eNOS) in human umbilical vein endothelial cells (HUVECs). NJE might act on a glucagon like peptide‐1 receptor (GLP‐1R) via Ca2+/calmodulin‐dependent protein kinase kinase β (CaMKKβ)‐AMPK signaling with pretreatment of their inhibitors or antagonist in HUVECs. Deacetylasperulosidic acid (DAA) was an active compound in noni juice to improve NO release through same pathway in HUVECs. These results suggested that noni is a novel dietary plant that probably regulates GLP‐1R‐induced CaMKKβ‐AMPK‐eNOS pathway to improve endothelium‐dependent relaxation, thus reduce the blood pressure probably via one of its responsible ingredient DAA.  相似文献   

9.
Angiogenesis plays an important role in a wide range of physiological processes such as wound healing and fetal development. In fact, many diseases are associated with imbalance in the regulation of angiogenesis in which there is either excessive or insufficient blood vessel formation. Panax notoginseng, a blood circulation invigorating herb, is commonly used in traditional Chinese medicine to treat circulation‐related diseases. However, the biological effects of saponin extract from Panax notoginseng (PNS) on angiogenesis and the underlying mechanisms are yet to be fully elucidated. This investigation describes the angiogenic effects of PNS on human umbilical vein endothelial cells (HUVECs) in vitro and zebrafish in vivo. The 2,3‐bis(2‐methoxy‐4‐nitro‐5‐sulfophenyl)5[(phenylamino)carbonyl]2H‐tetrazolium hydroxide (XTT) assay and microscopic cell counting demonstrated that the extract was able to stimulate the proliferation of HUVECs. Meanwhile, the numbers of invaded cells and tube branches were significantly increased in PNS treatment groups. PNS was also shown to promote changes in the subintestinal vessels, a feature of angiogenesis, in zebrafish. In addition, by using real‐time polymerase chain reaction (PCR), PNS was found to enhance vascular endothelial growth factor (VEGF) and kinase‐domain region/fetal liver kinase‐1 in mice (KDR/Flk‐1) mRNA expression, and the PNS‐induced HUVECs proliferation could be abolished by a KDR/Flk‐1 inhibitor. Furthermore, the proliferation of HUVECs induced by PNS was significantly attenuated by inhibitors of PI3K‐Akt‐eNOS. All the results suggest that PNS can promote angiogenesis, and that the proangiogenic effects involve the VEGF‐KDR/Flk‐1 and PI3K‐Akt‐eNOS signaling pathways. Copyright © 2008 John Wiley & Sons, Ltd.  相似文献   

10.

Aim of the study

Gomisin A (GA) is a small molecular weight lignan contained in Fructus Schisandrae, the dried seed of Schisandra chinensis which is widely used as a tonic in traditional Korean medicine. We previously demonstrated that GA induces endothelium-dependent and -independent relaxation in rat thoracic aorta, however the signaling pathways involved was not clarified. In this study, we examined whether GA could actually induce nitric oxide (NO) production and clarified the mechanism in cultured human coronary artery endothelial cells (HCAEC).

Results

Treatment of HCAEC with GA induced NO production in a time- and concentration-dependent manner in association with an enhanced endothelial NO synthase (eNOS) activity with an increased cytosolic translocation of eNOS. Both GA-induced NO production and eNOS activation were attenuated by pretreatment of the cells with EGTA, an extracellular Ca2+ chelator, and BAPTA-AM, an intracellular Ca2+ chelator, but not by LY 294002, a PI3-kinase/Akt inhibitor, suggesting involvement of Ca2+. Furthermore, GA rapidly increased the intracellular Ca2+ concentration, which was abolished in Ca2+ free media.

Conclusion

Taken together, our results suggest that GA induces Ca2+-dependent activation and translocation of eNOS in HCAEC, events linked to NO production and thereby endothelial-dependent vasorelaxation.  相似文献   

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