Protective Effects of Hyperoside from Hawthorn against Endothelia Cell Apoptosis Induced by H2O2

2011 ◽  
Vol 343-344 ◽  
pp. 1007-1014
Author(s):  
Ya Kun Ge ◽  
Xiao Xiang Zheng
Keyword(s):  
Endothelial Cell ◽  
Transmembrane Potential ◽  
Flavonol Glycoside ◽  
Mitochondrial Transmembrane Potential ◽  
Protective Effects ◽  
Cell Protection ◽  
Intracellular Ros ◽  
Apoptosis And Necrosis ◽  
Oxidative Effect

Hyperoside is a flavonol glycoside extraction from Hawthorn (Crataegus), and it has been reported that hyperoside process anti-inflammatory and anti-oxidative effectin vivo. In this paper, we studied the effects of hyperoside on apoptosis, necrosis, intracellular ROS level, mitochondrial transmembrane potential, and expression of Bax and Bcl-2 of endothelial cells subjected to H2O2,. The results showed that hyperoside treatment (50 μmol/L and 200 μmol/L ) significantly reduced apoptosis and necrosis, intracellular ROS and the expression of Bax in endothelial cell subjected to H2O2, and increased mitochondrial transmembrane potential and Bcl-2 expression. In conclusion, the present study indicates that hyperoside is in favor of endothelial cell protection.

scholarly journals The Novel Antioxidant Compound JSH-23 Prevents Osteolysis by Scavenging ROS During Both Osteoclastogenesis and Osteoblastogenesis

2021 ◽  
Vol 12 ◽  
Author(s):  
Liangwei Mei ◽  
Yi Zheng ◽  
Teng Ma ◽  
Bing Xia ◽  
Xue Gao ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Ros Generation ◽  
Protective Effects ◽  
Bone Homeostasis ◽  
Skeletal Disease ◽  
Antioxidant Compound ◽  
Intracellular Ros ◽  
Enhanced Expression ◽  
Induced Apoptosis

Inflammatory osteolysis is a pathological skeletal disease associated with not only the production of inflammatory cytokines but also local oxidative status. Excessive reactive oxygen species (ROS) promote bone resorption by osteoclasts and induce the apoptosis of osteoblasts. In consideration of the lack of effective preventive or treatments options against osteolysis, the exploitation of novel pharmacological compounds/agents is critically required. In our study, we found that a novel antioxidant compound, JSH-23, plays a role in restoring bone homeostasis by scavenging intracellular ROS during both osteoclastogenesis and osteoblastogenesis. Mechanically, JSH-23 suppressed RANKL-induced osteoclastogenesis, bone resorption and the expression of specific genes (including NFATc1, c-Fos, TRAP, CTSK and DC-STAMP) via inhibition of the NF-κB signaling pathway. Meanwhile, JSH-23 suppressed RANKL-induced ROS generation via the TRAF6/Rac1/NOX1 pathway and the enhanced expression of Nrf2/HO-1. In addition, JSH-23 attenuated H2O2-induced apoptosis and mineralization reduction in osteoblasts by reducing ROS production and enhancing Nrf2/HO-1 expression. Our in vivo results further revealed that JSH-23 exerts its protective effects on bone mass through its antioxidant activity. In conclusion, our results show that the application of JSH-23 might be a novel and plausible strategy for the treatment of osteolysis-related disease.

scholarly journals Mechanisms of endothelial cell protection by blockade of the JAK2 pathway

2007 ◽  
Vol 292 (3) ◽  
pp. C1123-C1131 ◽  
Author(s):  
Fernando Neria ◽  
Carlos Caramelo ◽  
Héctor Peinado ◽  
Francisco R. González-Pacheco ◽  
Juan JP. Deudero ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Nuclear Translocation ◽  
Kinase Inhibitor ◽  
Glycogen Synthase ◽  
Serum Deprivation ◽  
Dominant Negative ◽  
Protective Effects ◽  
Cell Protection ◽  
Phosphorylated Akt ◽  
Jak2 Inhibition

Inhibition of the JAK2/STAT pathway has been implicated recently in cytoprotective mechanisms in both vascular smooth muscle cells and astrocytes. The advent of JAK2-specific inhibitors provides a practical tool for the study of this pathway in different cellular types. An interest in finding methods to improve endothelial cell (EC) resistance to injury led us to examine the effect of JAK2/STAT inhibition on EC protection. Furthermore, the signaling pathways involved in JAK2/STAT inhibition-related actions were examined. Our results reveal, for the first time, that blockade of JAK2 with the tyrosine kinase inhibitor AG490 strongly protects cultured EC against cell detachment-dependent death and serum deprivation and increases reseeding efficiency. Confirmation of the specificity of the effects of JAK2 inhibition was attained by finding protective effects on transfection with a dominant negative JAK2. Furthermore, AG490 blocked serum deprivation-induced phosphorylation of JAK2. In terms of mechanism, treatment with AG490 induces several relevant responses, both in monolayer and detached cells. These mechanisms include the following: 1) Increase and nuclear translocation of the active, dephosphorylated form of β-catenin. In functional terms, this translocation is transcriptionally active, and its protective effect is further supported by the stimulation of EC cytoprotection by transfectionally induced excess of β-catenin. 2) Increase of platelet endothelial cell adhesion molecule (PECAM)/CD31 levels. 3) Increase in total and phosphorylated AKT. 4) Increase in phosphorylated glycogen synthase kinase (GSK)3α/β. The present findings imply potential practical applications of JAK2 inhibition on EC. These applications affect not only EC in the monolayer but also circulating detached cells and involve mechanistic interactions not previously described.

In Vitro Assessment of Cytoprotective Effects of CANOVA against Cell Death Induced by the Anti-malarial Artesunate – A Preliminary Experiment

Homeopathy ◽  
2021 ◽  
Author(s):  
Laís Teixeira Bonfim ◽  
Marcelo de Oliveira Bahia
Keyword(s):  
Cell Death ◽  
Fluorescent Dyes ◽  
Vero Cells ◽  
Negative Control ◽  
Protective Effects ◽  
Synthetic Compound ◽  
Cell Functions ◽  
Apoptosis And Necrosis

Abstract Background Artesunate (ATS) is a semi-synthetic compound derived from artemisinin, which is widely accepted in the treatment of malaria. However, there is evidence that ATS, under certain in vitro conditions, induces several impairments to normal cell functions. Canova (CA) is a Brazilian homeopathic formulation indicated for patients with depressed immune system. CA shows both in vitro and in vivo protective effects against mutagenic/carcinogenic compounds. Therefore, we aimed to assess in vitro the cytoprotective effects of CA against the cytotoxicity of ATS in Vero cells. Methods Viability of Vero cells exposed to ATS was assessed by MTT assay, whereas the anti-cytotoxic effect of CA was evaluated by apoptosis and necrosis quantification with fluorescent dyes. Results After 24 hours of ATS treatment, a reduction in cell viability was observed at 32 and 64 µg/mL, the latter being statistically significant (p < 0.05) in relation to the negative control. The concentration of 64 µg/mL was chosen for the subsequent experiments. ATS significantly induced both apoptosis and necrosis in Vero cells in relation to controls (p < 0.01). We also observed a statistically significant decrease in the number of apoptotic cells observed in the CA 16% + ATS co-treatment compared with ATS treatment (p < 0.01). Treatment with CA alone also had no influence on either type of cell death. Conclusion Our results demonstrated that ATS is cytotoxic in the assessed conditions. However, such cytotoxicity was attenuated when the cells were treated simultaneously with ATS and CA.

scholarly journals Endothelial Cell Autophagy in Atherosclerosis is Regulated by miR-30-Mediated Translational Control of ATG6

2015 ◽  
Vol 37 (4) ◽  
pp. 1369-1378 ◽  
Author(s):  
Tao Zhang ◽  
Feng Tian ◽  
Jing Wang ◽  
Jing Jing ◽  
Shan-Shan Zhou ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Translational Control ◽  
Cell Injury ◽  
Protein Translation ◽  
Luciferase Reporter ◽  
Protective Effects ◽  
Bioinformatics Analyses

Background/Aims: Endothelial cell injury and subsequent death play an essential role in the pathogenesis of atherosclerosis. Autophagy of endothelial cells has a protective role against development of atherosclerosis, whereas the molecular regulation of endothelial cell autophagy is unclear. MicroRNA-30 (miR-30) is a known autophagy suppressor in some biological processes, while it is unknown whether this regulatory axis may be similarly involved in the development of atherosclerosis. Here, we aimed to answer these questions in the current study. Methods: We examined the levels of endothelial cell autophagy in ApoE (-/-) mice suppled with high-fat diet (HFD), a mouse model for atherosclerosis (simplified as HFD mice). We analyzed the levels of autophagy-associated protein 6 (ATG6, or Beclin-1) and the levels of miR-30 in the purified CD31+ endothelial cells from mouse aorta. Prediction of the binding between miR-30 and 3'-UTR of ATG6 mRNA was performed by bioinformatics analyses and confirmed by a dual luciferase reporter assay. The effects of miR-30 were further analyzed in an in vitro model using oxidized low-density lipoprotein (ox-LDL)-treated human aortic endothelial cells (HAECs). Results: HFD mice developed atherosclerosis in 12 weeks, while the control ApoE (-/-) mice that had received normal diet (simplified as NOR mice) did not. Compared to NOR mice, HFD mice had significantly lower levels of endothelial cell autophagy, resulting from decreases in ATG6 protein, but not mRNA. The decreases in ATG6 in endothelial cells were due to HFD-induced increases in miR-30, which suppressed the translation of ATG6 mRNA via 3′-UTR binding. These in vivo findings were reproduced in vitro on ox-LDL-treated HAECs. Conclusion: Upregulation of miR-30 by HFD may impair the protective effects of endothelial cell autophagy against development of atherosclerosis through suppressing protein translation of ATG6.

scholarly journals Therapeutic and Radiosensitizing Effects of Armillaridin on Human Esophageal Cancer Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Chih-Wen Chi ◽  
Chien-Chih Chen ◽  
Yu-Jen Chen
Keyword(s):  
Cell Cycle ◽  
Esophageal Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Transmembrane Potential ◽  
Mitochondrial Transmembrane Potential ◽  
Cell Counts ◽  
Human Esophageal Cancer ◽  
Esophageal Cancer Cells

Background. Armillaridin (AM) is isolated fromArmillaria mellea. We examined the anticancer activity and radiosensitizing effect on human esophageal cancer cells.Methods. Human squamous cell carcinoma (CE81T/VGH and TE-2) and adenocarcinoma (BE-3 and SKGT-4) cell lines were cultured. The MTT assay was used for cell viability. The cell cycle was analyzed using propidium iodide staining. Mitochondrial transmembrane potential was measured by DiOC6(3) staining. The colony formation assay was performed for estimation of the radiation surviving fraction. Human CE81T/VGH xenografts were established for evaluation of therapeutic activityin vivo.Results. AM inhibited the viability of four human esophageal cancer cell lines with an estimated concentration of 50% inhibition (IC50) which was 3.4–6.9 μM. AM induced a hypoploid cell population and morphological alterations typical of apoptosis in cells. This apoptosis induction was accompanied by a reduction of mitochondrial transmembrane potential. AM accumulated cell cycle at G2/M phase and enhanced the radiosensitivity in CE81T/VGH cells.In vivo, AM inhibited the growth of CE81T/VGH xenografts without significant impact on body weight and white blood cell counts.Conclusion. Armillaridin could inhibit growth and enhance radiosensitivity of human esophageal cancer cells. There might be potential to integrate AM with radiotherapy for esophageal cancer treatment.

scholarly journals Effects of the Mitochondria-Targeted Antioxidant Mitoquinone in Murine Acute Pancreatitis

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Wei Huang ◽  
Nicole Cash ◽  
Li Wen ◽  
Peter Szatmary ◽  
Rajarshi Mukherjee ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Polymorphonuclear Leukocytes ◽  
Serum Amylase ◽  
Pancreatic Acinar Cells ◽  
Protective Effects ◽  
Intracellular Ros ◽  
Plate Reader ◽  
Acute Increase

Although oxidative stress has been strongly implicated in the development of acute pancreatitis (AP), antioxidant therapy in patients has so far been discouraging. The aim of this study was to assess potential protective effects of a mitochondria-targeted antioxidant, MitoQ, in experimental AP usingin vitroandin vivoapproaches. MitoQ blocked H2O2-induced intracellular ROS responses in murine pancreatic acinar cells, an action not shared by the control analogue dTPP. MitoQ did not reduce mitochondrial depolarisation induced by either cholecystokinin (CCK) or bile acid TLCS, and at 10 µM caused depolarisationper se. Both MitoQ and dTPP increased basal and CCK-induced cell death in a plate-reader assay. In a TLCS-induced AP model MitoQ treatment was not protective. In AP induced by caerulein hyperstimulation (CER-AP), MitoQ exerted mixed effects. Thus, partial amelioration of histopathology scores was observed, actions shared by dTPP, but without reduction of the biochemical markers pancreatic trypsin or serum amylase. Interestingly, lung myeloperoxidase and interleukin-6 were concurrently increased by MitoQ in CER-AP. MitoQ caused biphasic effects on ROS production in isolated polymorphonuclear leukocytes, inhibiting an acute increase but elevating later levels. Our results suggest that MitoQ would be inappropriate for AP therapy, consistent with prior antioxidant evaluations in this disease.

Endogenous hydrogen sulfide sulfhydrates IKKβ at cysteine 179 to control pulmonary artery endothelial cell inflammation

2019 ◽  
Vol 133 (20) ◽  
pp. 2045-2059 ◽  
Author(s):  
Da Zhang ◽  
Xiuli Wang ◽  
Siyao Chen ◽  
Selena Chen ◽  
Wen Yu ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Endothelial Cell ◽  
Pulmonary Artery ◽  
Cell Model ◽  
Site Directed Mutagenesis ◽  
Critical Event ◽  
Hypertensive Rats ◽  
Pulmonary Artery Endothelial Cell

Abstract Background: Pulmonary artery endothelial cell (PAEC) inflammation is a critical event in the development of pulmonary arterial hypertension (PAH). However, the pathogenesis of PAEC inflammation remains unclear. Methods: Purified recombinant human inhibitor of κB kinase subunit β (IKKβ) protein, human PAECs and monocrotaline-induced pulmonary hypertensive rats were employed in the study. Site-directed mutagenesis, gene knockdown or overexpression were conducted to manipulate the expression or activity of a target protein. Results: We showed that hydrogen sulfide (H2S) inhibited IKKβ activation in the cell model of human PAEC inflammation induced by monocrotaline pyrrole-stimulation or knockdown of cystathionine γ-lyase (CSE), an H2S generating enzyme. Mechanistically, H2S was proved to inhibit IKKβ activity directly via sulfhydrating IKKβ at cysteinyl residue 179 (C179) in purified recombinant IKKβ protein in vitro, whereas thiol reductant dithiothreitol (DTT) reversed H2S-induced IKKβ inactivation. Furthermore, to demonstrate the significance of IKKβ sulfhydration by H2S in the development of PAEC inflammation, we mutated C179 to serine (C179S) in IKKβ. In purified IKKβ protein, C179S mutation of IKKβ abolished H2S-induced IKKβ sulfhydration and the subsequent IKKβ inactivation. In human PAECs, C179S mutation of IKKβ blocked H2S-inhibited IKKβ activation and PAEC inflammatory response. In pulmonary hypertensive rats, C179S mutation of IKKβ abolished the inhibitory effect of H2S on IKKβ activation and pulmonary vascular inflammation and remodeling. Conclusion: Collectively, our in vivo and in vitro findings demonstrated, for the first time, that endogenous H2S directly inactivated IKKβ via sulfhydrating IKKβ at Cys179 to inhibit nuclear factor-κB (NF-κB) pathway activation and thereby control PAEC inflammation in PAH.

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