Umbilical Vein Endothelial Cells Damage Research Articles

Circ_0033596 depletion ameliorates oxidized low-density lipoprotein-induced human umbilical vein endothelial cell damage.

Previous data have shown that circ_0033596 is involved in the pathogenesis of atherosclerosis (AS). The study aims to reveal the detailed mechanism of circ_0033596 in AS. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL) to establish an AS cell model. Quantitative real-time polymerase chain reaction and western blot were implemented to detect the expression of circ_0033596, miR-637, growth factor receptor bound protein2 (GRB2), BCL2-associated x protein (Bax) and B-cell lymphoma-2 (Bcl-2). Cell viability, proliferation, apoptosis and tube formation were investigated by cell counting kit-8, EdU assay, flow cytometry and tube formation assay, respectively. The production of interleukin (IL-6) and tumor necrosis factor-α (TNF-α) was evaluated by enzyme-linked immunosorbent assay. Oxidative stress was evaluated by lipid peroxidation malondialdehyde assay kit and superoxide dismutase activity assay kit. Dual-luciferase reporter assay, RNA pull-down assay and RIP assay were performed to identify the associations among circ_0033596, miR-637 and GRB2. The expression of circ_0033596 and GRB2 was significantly increased, while miR-637 was decreased in the blood of AS patients and ox-LDL-induced HUVECs compared with controls. Ox-LDL treatment inhibited HUVEC viability, proliferation and angiogenic ability and induced cell apoptosis, inflammation and oxidative stress, while these effects were attenuated after circ_0033596 knockdown. Circ_0033596 interacted with miR-637 and regulated ox-LDL-induced HUVEC damage by targeting miR-637. In addition, GRB2, a target gene of miR-637, participated in ox-LDL-induced HUVEC injury by combining with miR-637. Importantly, circ_0033596 activated GRB2 by interacting with miR-637. Circ_0033596 depletion protected against ox-LDL-induced HUVEC injury by miR-637/GRB2 pathway, providing a therapeutic target for AS.

Kavalactones isolated from Alpinia zerumbet (Pers.) Burtt. et Smith with protective effects against human umbilical vein endothelial cell damage induced by high glucose

A new kavalactone, 4'-hydroxyl dihydro-5, 6-dehydrokavain (1) was isolated from the petroleum ether partition of leaves of Alpinia zerumbet (Pers.) Burtt. et Smith, together with four known kavalactone dimers, rel-1,trans-3-bis-(4-methoxy-2-oxopyran-6-yl)-cis-2,trans-4-diphenyl cyclobutene (2), aniba dimer A (3), aniba dimer C (4), 6,6'-(3,4-diphenylcyclobutane-1,2-diyl)bis(4-methoxy-2H-pyran-2-one (5). The structure of compound 1 was characterized by its MS, 1D-NMR, and 2D-NMR data, and the structures of the known compounds were determined by comparison of their spectroscopic data with those reported by the literatures. The obtained compounds were evaluated for their protective activities on human umbilical vein endothelial cells (HUVECs) damaged by high glucose (35 mM, cell viability at 70.10%). Compounds 3 and 5 could increase the cell viability at the concentration of 12.5 μΜ (83.12%) and 25 μΜ (75.02%), whereas at the concentration of 12.5 μΜ, compounds 1, 2, and 4 didn’t reverse cell damage (cell viability at 38.58%, 54.80% and 58.16%).

Celastrol attenuates angiotensin II mediated human umbilical vein endothelial cells damage through activation of Nrf2/ERK1/2/Nox2 signal pathway

Angiotensin II (Ang II), as a crucial factor of endothelial dysfunction, participates in endothelial oxidative damage and inflammation, which is present in all cardiovascular disease (CVD). Celastrol, extracted from Trypterygiun wilfordii Hook F. (“Thunder of God Vine”), is a natural compound with antioxidant and anti-inflammatory activities. In this study, the protective effects of celastrol on human umbilical vein endothelial cell (HUVEC) injury induced by Ang II were observed and its mechanisms were elucidated. Compared with the control group, Ang II significantly increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, enhanced reactive oxygen species levels and proinflammatory cytokines, decreased antioxidant enzyme activities, and suppressed cellular viability and promoted cell apoptosis. It accomplished this via inhibition of the nuclear factor erythroid 2–related factor 2 (Nrf2), increasing the expression levels of Nox2 and AngII type 1 receptor (AT1 receptor), and inducing the phosphorylation of extracellular signal regulated kinase (ERK1/2). In contrast, celastrol effectively suppressed reactive oxygen species generation, improved endothelial cell activity, and ameliorated Ang II-mediated HUVEC injury through activation of Nrf2, inhibition of Nox2/AT1 receptor expression, and upregulated phosphorylation of ERK1/2. After treatment with brusatol, a specific inhibitor of Nrf2, the protective effects of celastrol on Ang II-induced damage in HUVECs were remarkably alleviated. Taken together, celastrol-induced activation of Nrf2 and inhibition of NADPH oxidase activity were critical for the inhibition of Ang II-mediated endothelial dysfunction, and demonstrated the potential application of celastrol in CVD therapy.

Therapeutic Effects of Cyathula officinalis Kuan and Its Active Fraction on Acute Blood Stasis Rat Model and Identification Constituents by HPLC-QTOF/MS/MS.

Background:Cyathula officinalis Kuan is widely used in the clinics for the treatment of blood stasis in China.Objective:To evaluate the improving blood rheology and anti-inflammatory properties of C. officinalis Kuan extract (CO) and its active fraction (ACO) on acute blood stasis model Wistar rats and characterize the correlative constituents.Materials and Methods:CO at 0.26, 0.53, and 1.04 g/kg and ACO at 0.38, 0.75, and 1.5 g/kg were administered to acute blood stasis model Wistar rats for 3 days. Whole blood viscosity, plasma viscosity, and the levels of interleukin-6 (IL-6), nitric oxide (NO), tumor necrosis factor alpha (TNF-α), and cyclooxygenase-2 (COX-2) in the plasma were measured. HPLC-QTOF/MS/MS method was used to identify the major constituents of ACO; the properties of two representative components (cyasterone and chikusetsusaponin IV) from ACO on thrombin-induced human umbilical vein endothelial cells damage model were also assessed by the levels of thromboxane A2 (TXA2), endothelin (ET), malondialdehyde (MDA), COX-2, endothelial nitric oxide synthase (eNOS), and superoxide dismutase (SOD).Results:CO and ACO significantly reduced whole blood viscosity, plasma viscosity, and levels of IL-6, NO, TNF-α, and COX-2 in vivo. Forty compounds were identified from ACO, mainly as phytoecdysteroids and saponins. Cyasterone and chikusetsusaponin IV could significantly inhibit levels of TXA2, ET, MDA, and COX-2 and promote the activities of eNOS and SOD in vitro.Conclusion:CO and ACO possessed significant improving blood rheology and anti-inflammatory effects on acute blood stasis model rats and the representative components Cyasterone and chikusetsusaponin IV showed significant anti-inflammatory, antioxidant, and anticoagulant effects in vitro.SUMMARY Cyathula officinalis Kuan is widely used in the clinic for the treatment of blood stasis in ChinaThe C. officinalis Kuan extract and the active fraction of C. officinalis Kuan (ACO) possessed significant improving blood rheology and anti-inflammatory effects on acute blood stasis model ratsForty compounds were identified from ACO, mainly as phytoecdysteroids and saponins Abbreviations used: TCM: Traditional Chinese Medicine, CO: Cyathula officinalis Kuan extract, ACO: Active fraction of Cyathula officinalis Kuan, ROS: Reactive oxygen species, IL-6: Interleukin-6, TNF-α: Tumor necrosis factor alpha, NO: Nitric oxide, COX-2: Cyclooxygenase-2, TXA2: Thromboxane A2, ET: Endothelin, MDA: Malondialdehyde, eNOS: Endothelial nitric oxide synthase, SOD: Superoxide dismutase, ESI: Electronic spray ionization, ELISA: Enzyme-linked immunosorbent assay, HUVECs: Human umbilical vein endothelial cells, DMEM: Dulbecco's modified Eagle medium, MMP: Matrix metalloproteinase.

Protective effect of different solvent extracts from Platycladi Cacumen Carbonisatum on LPS-induced human umbilical vein endothelial cells damage

To study the protective effect of different solvent extracts from Platycladi Cacumen Carbonisatum (PCC) on LPS-induced human umbilical vein endothelial cell damage, and discuss the effective extracts from PCC for protecting vascular endothelial cells and their possible active substances. HUVECs were cultured in vitro; And LPS was adopted to establish the human umbilical vein endothelial cell damage model. MTT colorimetric method was used to determine cell activity; Xanthine oxidase method was adopted to detect the activity of superoxide dismutases (SOD) in the cell culture fluid; The TBA method was adopted to determine the content of malondialdehyde (MDA); The nitrate reductase method was used to detect the content of nitric oxide (NO); And UPLC/Q-TOF-MS was used to analyze the difference in flavonoids components among different solvent extracts from PCC. Compared with the model group, N-butanol extract (100 mg x L(-1)) and ethylacetate extract (100, 50 mg x L(-1)) could significantly enhance the cell activity (P < 0.05), significantly reduce MDA and NO content, and increase SOD activity (P < 0.05). Among the four solvent extracts, the content of total flavonids were the highest in ethyl acetate extract, the lowest in water extract and equivalent in N-butanol and petroleum benzene extract. In terms of the contents of quercitrin and myricitrin, N-butanol extract were second only to ethyl acetate extract. Ethylacetate extract from PCC has a notable antagonistic effect in the damage induced by LPS to HUVECs, and thus is the most effective extract from PCC in protecting vascular endothelial cells. Quercitrin, myricitrin or multiple flavonoids that it contains may be their active substances for protecting vascular endothelial cells. Its mechanism may be related to the decrease in the production of NO and the inhibition of lipid peroxidation in cells.

Protective Effects of Danggui Buxue Tang on a Human Umbilical Vein Endothelialcell Damage Induced by Advanced Glycation End Products

Advanced glycation end products (AGEs) have been regarded as a pivotal inducer in diabetes and kinds of diabetic nephropathy. The present studies explored the effects of Danggui Buxue Tang (DBT) that is a Chinese medicinal de- coction on negative charge to Human Umbilical Vein Endothelial Cell (HUVEC) and the related mechanism. Alcian blue staining was established to evaluate the intensity of negative charge on HUVEC. Proteoglycan expressions of AGP and avidin were determined by SDS-PAGE. We observed that DBT can significantly increase negative charge on HU-VEC and up-regulated AGP and avidin expressions and ameliorate AGEs-induced HUVEC apoptosis. Therefore, all results showed DBT had prevention effects against the progression of AGEs-induced damage, and this decoction might be promising agent against proteinuria in diabetic nephropathy.

Protective effects of hyperoside against human umbilical vein endothelial cell damage induced by hydrogen peroxide

Ethnopharmacological relevanceHyperoside (Hyp) is a flavonoid compound isolated from Rhododendron ponticum L. leaves that elicits vascular protective effects in vitro. Treatment with Hyp has been found to attenuate endothelial cell damage induced by oxidative stress, but its mechanisms of action remain unclear.This study investigated the action of Hyp in an endothelial injury model induced by hydrogen peroxide (H2O2), as well as its possible mechanisms. Materials and methodsHuman umbilical vein endothelial cells (HUVECs) were treated with H2O2 alone or in combination with Hyp. The protective effects of Hyp against H2O2 were evaluated, and the activation of extracellular signal-regulated protein kinase (ERK) in Hyp was assayed in HUVECs. ResultsLoss of cell viability as well as excessive cell apoptosis and death were observed in HUVECs after 18h of challenge with H2O2 (400μM); however, both cell apoptosis and death were attenuated in the Hyp-pretreated cells. Western blot analysis revealed that Hyp increased the expression of Bcl-2 but decreased that of Bax. In addition, Hyp induced the phosphorylation of ERK1/2 in HUVECs. ConclusionThese observations provide preliminary evidence that Hyp protects HUVECs against H2O2 damage, at least partially, by activating the ERK signaling pathway.

Two new 4-arylcoumarins from the seeds of Calophyllum polyanthum

Two new 4-arylcoumarins, 7,4′-dihydroxy-6,8-dimethoxy-4-phenylcoumarin (1) and 7-hydroxy-6,8,4′-trimethoxy-4-phenylcoumarin (2), together with four known compounds were isolated from the seeds of Calophyllum polyanthum. The structures of the new compounds were determined by extensive spectroscopic analyses, and the structure of compound 2 was confirmed by X-ray crystallography analysis. Both new compounds exhibited significant cell protective activities against H2O2-induced human umbilical vein endothelial cell damage.

Protective effect of total flavonoids from Spirodela polyrrhiza (L.) Schleid on human umbilical vein endothelial cell damage induced by hydrogen peroxide

In this study, we determined the protective effect of total flavonoids from Spirodela polyrrhiza (L.) Schleid (STF), which is a kind of traditional Chinese medicine, on human umbilical vein endothelial cells (ECV-304) damage induced by hydrogen peroxide (H 2O 2). Treated with 1 mmol/L H 2O 2 for 1 h, the viability of ECV-304 cells markedly decreased. However, pretreatment with 10–50 μg/mL STF resulted in a significant recovery. The survival rate of ECV-304 increased from 21.98% (only treated with 1 mmol/L H 2O 2) to 64.74% (pretreated with 50 μg/mL STF), which accompanied with the amounts of malondialdenhyde (MDA) decreasing from 1.6883 nmol/L to 0.9628 nmol/L. Furthermore, compared with control group, the 50 μmol/L STF pretreatment enhanced the total antioxidant capacity (T-AOC) by 4.49 times, increased the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) by 85.12%, 158.94% and 94.5%,respectively, and increased the content of nitric oxide (NO) by 116.55%.Taken together, STF protect ECV-304 cells against H 2O 2 damage by enhancing the antioxidant ability and increasing NO production.