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Scutellarin Reduces Cerebral Ischemia Reperfusion Injury Involving in vascular endothelium Protection and PKG Signal

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Natural Products and Bioprospecting 2021年第6期11卷 659-670页

作者： Ya-Juan Chen Chen Chen Meng-Yuan Li Qing-Qing Li Xiu-Juan Zhang Rong Huang Xing-Wei Zhu Chun-Yun Bai Liu-Yi Zhang Pei-Hua Peng Wei-Min Yang School of Pharmaceutical Science&Yunnan Key Laboratory of Pharmacology for Natural Products Kunming Medical University1168 Western Chunrong RoadYuhua StreetChenggong New CityKunming 650500China Department of Anesthesiology The First Affiliated Hospital of Kunming UniversityKunming 650032China

Flavonoid glycoside scutellarin(SCU)has been widely applied in the treatment of cerebral ischemic diseases in *** this article,we conducted research on the working mechanisms of SCU in hypoxia reoxygenation(HR)injury of isolated cerebral basilar artery(BA)and erebral ischemia reperfusion(CIR)injury in rat *** isolated rat BA rings,HR causes endothelial dysfunction(ED)and acetylcholine(ACh)induces endothelium-dependent *** myography result showed that SCU(100μM)was able to significantly improve the endothelium-dependent vasodilation induced by ***,SCU did not affect the ACh-induced relaxation in normal *** studies suggested that SCU(10-1000μM)dose-dependently induced relaxation in isolated BA rings which were significantly blocked by the cGMP dependent protein kinase(PKG)inhibitor Rp-8-Br-cGMPs(PKGI-rp,4μM).Pre-incubation with SCU(500μM)reversed the impairment of endothelium-dependent vasodilation induced by HR,but the reversing effect was blocked if PKGI-rp(4μM)was *** brain slice staining test in rats’model of middle cerebral artery occlusion(MCAO)induced CIR proved that the administration of SCU(45,90 mg/kg,iv)significantly reduced the area of cerebral *** Western blot assay result showed that SCU(45 mg/kg,iv)increased brain PKG activity and PKG protein level after CIR *** conclusion,our findings suggested that SCU possesses the ability of protecting brain cells against CIR injury through vascular endothelium protection and PKG signal.

关键词： Scutellarin Basilar artery vascular endothelium Ischemia reperfusion PKG

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Phytoestrogen genistein decreases contractile response of aortic artery in vitro and arterial blood pressure in vivo

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Acta Pharmacologica Sinica 2004年第3期25卷 59-64页

作者： Hong-fang LI1,Long-de WANG2,Song-yi QU Department of Physiology,Lanzhou Medical College,Lanzhou 730000 2Affiliated Hospital,Gansu Chinese Medical College,Lanzhou 730020,China Department of Physiology Lanzhou Medical College Lanzhou 730000 Affiliated Hospital Gansu Chinese Medical College Lanzhou 730020

AIM: To determine the mechanisms of effects of phytoestrogen genistein on the contracted rabbit aortic arteries in vitro, and observe the effect of genistein and 17-β estradiol on mean arterial pressure (MAP) in ovariectomized (OVX) rats. METHODS: (1) Strips of rabbit aortic smooth muscle were suspended in organ baths containing Kreb’s solution, and then isometric tension was measured. (2) Female mature Wistar rats underwent a bilateral ovariectomy (OVX). Sham-operated rats (SHAM) were used as controls. After administration of genistein (0.4 mg·kg-1·d-1, sc), 17-β estradiol (1 mg·kg-1·d-1, sc) or theirvehicle sesame oil for 21 d,MAP was measured. RESULTS: (1) Similar to 17-β estradiol, genistein could dose-dependently relax 40 mmol/L KCl-precontracted arterial strips. Incubation with Nω-L-nitro-arginine (L-NNA), methylene blue (MB), indomethacin, propranolol or endothelium removal did not affect relaxation induced by genistein. In calcium-free solution containing 0.01mmol/L egtazic acid (EGTA), genistein inhibited not only the first phase contraction induced by noradrenaline (NA), but also the second contraction induced by CaCl2. In addition, genistein could reduce the contractile responses of NA, KCl and CaCl2, and shift their cumulative concentration-response curves rightward. (2) MAP in OVX rats was significantlyhigher compared with that of SHAM rats. However,after chronically treatment with genistein or 17-β estradiol for 21 d the baseline MAP in OVX rats was reduced significantly. CONCLUSIONS: (1) The vasodilator effect of genistein in vitro is endothelium independent and not related to the nitric oxide, its mechanisms being probably due to inhibition of Ca2+ influx through calcium channels in a noncompetitive manner and Ca2+ release from intracellular store induced by NA. (2) Administration of genistein or 17-β estradiol can chronically decrease MAP in OVX rats.

关键词： genistein aorta smooth muscle muscle relaxation calciumchannel vascular endothelium blood pressure

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Integrin β4 mAb inhibited apoptosis induced by deprivation of growth factors in vascular endothelial cells

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Acta Pharmacologica Sinica 2004年第6期25卷 31-35页

作者： Ke-wen ZHAO, Qi-tao ZHAO, Shang-li ZHANG, Jun-ying MIAO2 Institute of Developmental Biology, School of Life Science, Shandong University, Ji-nan 250100, China Institute of Developmental Biology School of Life Science Shandong University Jinan 250100

AIM: To understand the mechanism by which anti-β4 integrin monoclonal antibody (mAb) inhibits apoptosis of vascular endothelial cells (VEC). METHODS: Viability was determined by counting the cells that attached to dishes after treatments. DNA fragmentation was analyzed by agarose gel electrophoresis and fluorescence microscopy. The intracellular content of cAMP was measured by radioimmunoassay (RIA). The levels of p53 and Ras expres- sions were analyzed by fluorescence microscopy combined with immunofluorescence under laser scanning confo- cal microscopy. RESULTS: After the cells were deprived of fibroblast growth factor (FGF) and serum were exposed to the mAb 5 mg/L for 24 h, the detachment and DNA fragmentation of these cells were suppressed. When cells were deprived of FGF and serum, the intracellular cAMP level and Ras protein content decreased (P<0.05), while the level of p53 protein expression increased (P<0.05). But in the presence of anti-β4 integrin mAb, VEC apoptosis was inhibited, and at the same time, the changes mentioned above were obviously blocked (P<0.05). CONCLUSION: Anti-4 integrin mAb inhibited apoptosis by affecting the level of cAMP, and blocking down- regulation of Ras protein and up-regulation of p53 protein in VEC.

关键词： integrin 4 monoclonal antibodies apoptosis umbilical veins vascular endothelium cyclic AMP protein p53 ras genes

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Therapeutic neovascularization by autologous transplantation with expanded endothelial progenitor cells from peripheral blood into ischemic hind limbs

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Acta Pharmacologica Sinica 2005年第9期26卷 1069-1075页

作者： Chun-ling FAN Ping-jin GAO Zai-qian CHE Jian-jun LIU Jian WEI Ding-liang ZHU~2 Shanghai Key Laboratory Of vascular Biology,Shanghai Institute of Hypertension,Ruijin Hospital,Shanghai Second Medical University and National Key Laboratory for Medical Genomics,Health Science Center,Shanghai Institute for Biological Sciences,Chinese Academy of Sciences,Shanghai 200025,China Shanghai Key Laboratory of vascular Biology Shanghai Institute of Hypertension Ruijin Hospital Shanghai Second Medical University and National Key Laboratory for Medical Genomics Health Science Center Shanghai Institute for Biological Sciences Chinese Academy of Sciences Shanghai China

Aim:To investigate the hypothesis that transplantation with expanded autolo-gous endothelial progenitor cells(EPC)could enhance ***:Peripheral blood mononuclear cells(PB-MNC)isolated from New ZealandWhite rabbits were cultured in *** d 7,the adherent cells were collected forautologous *** with severe unilateral hind limb ischemiawere randomly assigned to receive phosphate-buffered saline or expanded EPC inphosphate-buffered saline,administered by intramuscular injection in 6 sites ofthe ischemic thigh at postoperative d *** was monitored byusing the calf blood pressure ratio to indicate tissue perfusion,digital subtractionangiography to identify collateral vessel development and histological analysisof capillary density in the ischemic limb at d 35 after ***:Autolo-gous EPC transplantation produced significant amelioration in ischemic hind limbs,as indicated by a greater calf blood pressure ratio(0.52±0.04 vs 0.42±0.05,Pvascularization in ischemichindlimbs.

关键词： vascular endothelium hindlimb ischemia physiologic neovascularization stem cell transplantation

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(-)Epicatechin induces and modulates endothelium-dependent relaxation in isolated rat mesenteric artery rings

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Acta Pharmacologica Sinica 2002年第12期23卷 135-139页

作者： CHAN Franky Leung China Chinese University of Hong Kong Department of Anatomy

AIM: The present study was aimed to examine the role of endothelial nitric oxide in the relaxant response to green tea (-)epicatechin and its modulation of endothelium-mediated relaxation in the isolated rat mesenteric artery rings. METHODS: Changes in the isometric tension were measured with Grass force-displacement transducers. RESULTS: The (-)epicatechin-induced relaxation was largely dependent on the presence of intact endothelium and was re-versed by NG-nitro-L-arginine methyl ester 10 μmol/L or methylene blue 10 μmol/L, the inhibitors of nitric oxide-mediated relaxation. L-Arginine at 1 mmol/L antagonized the effect of L-NAME or methylene blue. Pretreatment of endothelium-intact rings with (-)epicatechin 10 μmol/L enhanced the relaxation induced by endothelium-dependent vasodilator, acetylcholine, while this concentration did not influence the endothelium-independent relaxation in-duced by sodium nitroprusside in the endothelium-denuded artery rings. CONCLUSION: The results indicate that the en

关键词： (-)epicatechin vascular endothelium nitric oxide muscle relaxation mesenteric artery rats

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Ascorbic acid improves impaired venous and arterial endotheliumdependent dilation in smokers

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Acta Pharmacologica Sinica 2005年第4期26卷 447-452页

作者： Márcio Goncalves de SOUSA Juan Carlos YUGAR-TOLEDO Marcelo RUBIRA Sílvia Elaine FERREIRA-MELO Rodrigo PLENTZ Deise BARBIERI Fernanda CONSOLIM-COLOMBO Maria Cláudia IRIGOYEN Heitor MORENO Jr Cardiovascular Pharmacology and Cardiology Clinical Hospital of Campinas and Faculty of Medical Sciences State University of Campinas 13081-970 Campinas S o Paulo Brazil Cardiovascular Pharmacology and Cardiology Clinical Hospital of Campinas and Faculty of Medical Sciences State University of Campinas 13081-970 Campinas S o Paulo Brazil Hypertension Unit InCor Clinical Hospital of S o Paulo Faculty of Medicine of S o Paulo University 05403-000 S o Paulo Brazil Cardiovascular Pharmacology and Cardiology Clinical Hospital of Campinas and Faculty of Medical Sciences State University of Campinas 13081-970 Campinas S o Paulo Brazil Hypertension Unit InCor Clinical Hospital of S o Paulo Faculty of Medicine of S o Paulo University 05403-000 S o Paulo Brazil Cardiovascular Pharmacology and Cardiology Clinical Hospital of Campinas and Faculty of Medical Sciences State University of Campinas 13081-970 Campinas S o Paulo Brazil Hypertension Unit InCor Clinical Hospital of S o Paulo Faculty of Medicine of S o Paulo University 05403-000 S o Paulo Brazil Hypertension Unit InCor Clinical Hospital of S o Paulo Faculty of Medicine of S o Paulo University 05403-000 S o Paulo Brazil Cardiovascular Pharmacology and Cardiology Clinical Hospital of Campinas and Faculty of Medical Sciences State University of Campinas 13081-970 Campinas S o Paulo Brazil

Aim:To compare the acute effects of ascorbic acid on vasodilation of veins andarteries in ***:Twenty-six healthy non-smokers and 23 healthy moder-ate smokers were recruited in this *** dorsal hand vein compliance tech-nique and flow-mediated dilation were ***-response curves to bradykininand sodium nitroprusside were constructed to test the endothelium-dependentand-independent relaxation before and after acute infusion of ascorbic ***:Smokers had an impaired venodilation with bradykinin compared withnon-smokers(68.3%±13.2% vs 93.7%±20.1%,respectively;Pendothelium-dependent dilation compared with that in non-smok-ers(8.8%±2.7% vs 15.2%±2.3%,respectively;Pendothelium-indepen-dent dilation did not differ in both the groups *** important hemody-namic change was detected using the Portapress ***:Smokershad impaired endothelium-dependent vasodilation responsiveness in both arte-rial and venous *** acid restores this responsiveness in smokers.

关键词： ascorbic acid vasodilation vascular endothelium arterioles venules dorsal hand vein flow-mediated dilation

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Modulation of P-glycoprotein function by amlodipine derivatives in brain microvessel endothelial cells of rats

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Acta Pharmacologica Sinica 2005年第2期26卷 166-170页

作者： Bian-sheng JI Ling HE Guo-qing LIU Department of Pharmacology,China Pharmaceutical University,Nanjing 210009,China Department of Pharmacology China Pharmaceutical University Nanjing China

Aim:To investigate whether the amlodipine derivatives,CJX1 and CJX2,havea modulative effect on P-glycoprotein(P-gp)function in rat brain microvesselendothelial cells(RBMEC).Methods:Isolated RBMEC were cultured in DMEM/F 12(1:1)*** amount of intracellular rhodamine(Rh123)was determined,using a fluorescence spectrophotometer,to evaluate the function of ***:The accumulation of Rh123 in RBMEC was potentiated in a concentration-dependent manner after incubation with CJX1 and CJX2 at 1,2.5,5,and 10μmol/L(P0.05).Accumulation of intracellular Rh123 was increased and efflux of intra-cellular Rh123 was decreased in a time-dependent manner from 0-100 min afterCJX1 and CXJ2 at 10 ∴mol/L *** inhibitory effect of CJX1 and CJX2on P-gp function was reversible and remained even at 120 min after removal ofCJX1 and CJX2 at 2.5μmol/L from the ***:CJX1 and CJX2exhibited a potent effect in the inhibition of P-gp function in vitro.

关键词： amlodipine derivatives CJX1 CJX2 verapamil P-glycoprotein blood brain barrier vascular endothelium

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Effect of Korea red ginseng on cerebral blood flow and superoxide production

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Acta Pharmacologica Sinica 2002年第12期23卷 99-103页

作者： CukSeong KIM,Jin Bong PARK,Kwang-Jin KIM,Seok Jong CHANG,Sung-Woo RYOO,Byeong Hwa JEON Department of Physiology College of Medicine Chungnam National University Taejon KOREA Department of Physiology College of Medicine Chungnam National University Taejon KOREA Department of Physiology College of Medicine Chungnam National University Taejon KOREA Department of Physiology College of Medicine Seonam University Namwon KOREA Division of Genomics ＆ Proteomics Korea Research Institute of Bioscience and Biotechnology(KRIBB) Yusong Taejon Korea Correspondence to Byeong Hwa JEON MD PhD.Department of Physiology College of Medicine Chungnam National University 6 Munhwa-dong Jung-gu Taejon South Korea 301131

AIM: To investigate the effects of Korea red ginseng (KRG) on the cerebral perfusion rate in the rats and the generation of superoxide anion in the endothelial cells. METHODS: The cerebral perfusion rate was measured using laser-doppler flowmetry before and after the administration of crude saponin (CS) and saponin-free fraction (SFF) of KRG in the anesthetized rats. The superoxide generation was measured by the method based on lucigenin-enhanced chemiluminescence in the cultured endothelial cells. RESULTS: The relative cerebral perfusion rate (rCBF) was significantly increased by the intraperitoneal injection of CS (100 mg/kg) in the rats, but SFF had no effect on the rCBF. Chronic treatment with CS for 7 d significantly inhibited the decrease of forebrain cerebral blood flow induced by clamping both carotid arteries in the rats. Furthermore, CS (0.1 g/L) significantly sup-pressed NADPH-induced superoxide generation in the human umbilical vein endothelial cells (P<0.01). CONCLUSION: The present study d

关键词： Korean red ginseng cerebral blood flow superoxides vascular endothelium

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Effects of Panax notoginseng saponins on vascular endothelial cells in vitro

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Acta Pharmacologica Sinica 2000年第12期21卷 46-50页

作者：关超然关加华 1200 Main street West Canada Faculty of Health Sciences Hamilton McMaster University Ontario L8N 3Z5 Smooth Muscle Research Program and Department of Medicine

AIM: To investigate the inhibition of endothelium-de-pendent in vitro vascular relaxation induced by the total saponins (gensenosides) from Panax notoginseng (PNS) and the effect of PNS on the cytosolic Ca2+ concentration on cultured bovine pulmonary artery endothelial cells. METHODS: The endothelial-dependent vascular relaxation was assessed using acetylcholine (ACh) or cyclopi-azonic acid (CPA) induced relaxation in endothelium-intact rat aorta. Cytosolic Ca2+ level was assessed in real time using dynamic digital fluorescence ratio imaging. RESULTS: In addition to its direct relaxation of the smooth muscle cells at high concentrations, PNS, at 100 mg/L having little effect on smooth muscle, caused a marked inhibition of endothelium-dependent relaxation brought about by PNS. This inhibitory effect was due to its inhibition of elevation of cytosolic Ca2+ , which is required for the activation of NO generation and release from the vascular endothelial cells. Nifedipine has no effect on either the endothe

关键词： Panax notoginseng saponins vascular endothelium smooth muscle relaxation

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Inhibitory effect of extracts of Ginkgo biloba leaveson VEGF-induced hyperpermeability of bovine coronary endothelial cells in vitro

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Acta Pharmacologica Sinica 2004年第10期 66-71页

作者： Yan QIU, Yao-cheng RUI, Tie-jun LI, Li ZHANG, Peng-yuan YANG Department of Pharmacology, School of Pharmacy, Second Medical Military University, Shanghai 200433, China

AIM: To study whether extract of Ginkgo biloba (EGb) can protect against atherosclerosis. METHODS: Confluent monolayers of bovine coronary endothelial cells (BCECs), bovine coronary smooth muscle cells (BCSMCs), and cocultures of the two were incubated with medium containing VEGF and/or EGb, and flux of 125I-labeled oxidized low density lipoprotein (ox-LDL) across the monolayers was measured. RESULTS: Incubation with VEGF significantly increased the permeability of BCEC monolayers to 125I-ox-LDL in a time- and concentration-dependent manner, but had no effect on permeability of BCSMCs or endothelial cells-smooth muscle cells cocultures. EGb significantly inhibited the VEGF-induced hyperpermeability of BCECs. CONCLUSION: VEGF was important in the formation and development of atherosclerosis. The inhibition of VEGF-induced permeability by EGb suggests that extracts of Ginkgo biloba leaves may have important clinical applications in the treatment of cardiovascular diseases.

关键词： Ginkgo biloba vascular endothelium coronary vessals vascular endothelial growth factor capillary permeability iodine radioisotopes LDL lipoproteins

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