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.

Cyanidin-3-glucoside attenuates 4-hydroxynonenal- and visible light-induced retinal damage in vitro and in vivo

2019 ◽  
Vol 10 (5) ◽  
pp. 2871-2880 ◽  
Author(s):  
Yong Wang ◽  
Wentao Qi ◽  
Yazhen Huo ◽  
Ge Song ◽  
Hui Sun ◽  
...  
Keyword(s):  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Retinal Damage ◽  
Protective Effects ◽  
Pigment Epithelial ◽  
Induced Apoptosis ◽  
Pigment Epithelial Cells

Cyanidin-3-glucoside has efficient protective effects on 4-hydroxynonenal-induced apoptosis, senescence, and angiogenesis in retinal pigment epithelial cells.

scholarly journals Evaluation of anticancer activity in vitro of a stable copper(I) complex with phosphine-peptide conjugate

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Urszula K. Komarnicka ◽  
Barbara Pucelik ◽  
Daria Wojtala ◽  
Monika K. Lesiów ◽  
Grażyna Stochel ◽  
...  
Keyword(s):  
A549 Cells ◽  
Ros Generation ◽  
Dependent Manner ◽  
Hacat Cells ◽  
Icp Ms ◽  
Intracellular Ros ◽  
M Phase ◽  
Lung Adenocarcinoma A549 ◽  
Induced Apoptosis

Abstract[CuI(2,9-dimethyl-1,10-phenanthroline)P(p-OCH3-Ph)2CH2SarcosineGlycine] (1-MPSG), highly stable in physiological media phosphino copper(I) complex—is proposed herein as a viable alternative to anticancer platinum-based drugs. It is noteworthy that, 1-MPSG significantly and selectively reduced cell viability in a 3D spheroidal model of human lung adenocarcinoma (A549), in comparison with non-cancerous HaCaT cells. Confocal microscopy and an ICP-MS analysis showed that 1-MPSG effectively accumulates inside A549 cells with colocalization in mitochondria and nuclei. A precise cytometric analysis revealed a predominance of apoptosis over the other types of cell death. In the case of HaCaT cells, the overall cytotoxicity was significantly lower, indicating the selective activity of 1-MPSG towards cancer cells. Apoptosis also manifested itself in a decrease in mitochondrial membrane potential along with the activation of caspases-3/9. Moreover, the caspase inhibitor (Z-VAD-FMK) pretreatment led to decreased level of apoptosis (more pronouncedly in A549 cells than in non-cancerous HaCaT cells) and further validated the caspases dependence in 1-MPSG-induced apoptosis. Furthermore, the 1-MPSG complex presumably induces the changes in the cell cycle leading to G2/M phase arrest in a dose-dependent manner. It was also observed that the 1-MPSG mediated intracellular ROS alterations in A549 and HaCaT cells. These results, proved by fluorescence spectroscopy, and flow cytometry, suggest that investigated Cu(I) compound may trigger apoptosis also through ROS generation.

scholarly journals Tetrahydrocurcumin Ameliorates Diabetic Cardiomyopathy by Attenuating High Glucose-Induced Oxidative Stress and Fibrosis via Activating the SIRT1 Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Kaifeng Li ◽  
Mengen Zhai ◽  
Liqing Jiang ◽  
Fan Song ◽  
Bin Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Diabetic Cardiomyopathy ◽  
High Glucose ◽  
Therapeutic Potential ◽  
Ros Generation ◽  
Protective Effects ◽  
Collagen Iii

Hyperglycemia-induced oxidative stress and fibrosis play a crucial role in the development of diabetic cardiomyopathy (DCM). Tetrahydrocurcumin (THC), a major bioactive metabolite of natural antioxidant curcumin, is reported to exert even more effective antioxidative and superior antifibrotic properties as well as anti-inflammatory and antidiabetic abilities. This study was designed to investigate the potential protective effects of THC on experimental DCM and its underlying mechanisms, pointing to the role of high glucose-induced oxidative stress and interrelated fibrosis. In STZ-induced diabetic mice, oral administration of THC (120 mg/kg/d) for 12 weeks significantly improved the cardiac function and ameliorated myocardial fibrosis and cardiac hypertrophy, accompanied by reduced reactive oxygen species (ROS) generation. Mechanically, THC administration remarkably increased the expression of the SIRT1 signaling pathway both in vitro and in vivo, further evidenced by decreased downstream molecule Ac-SOD2 and enhanced deacetylated production SOD2, which finally strengthened antioxidative stress capacity proven by repaired activities of SOD and GSH-Px and reduced MDA production. Additionally, THC treatment accomplished its antifibrotic effect by depressing the ROS-induced TGFβ1/Smad3 signaling pathway followed by reduced expression of cardiac fibrotic markers α-SMA, collagen I, and collagen III. Collectively, these finds demonstrated the therapeutic potential of THC treatment to alleviate DCM mainly by attenuating hyperglycemia-induced oxidative stress and fibrosis via activating the SIRT1 pathway.

Differential protective effects of Bcl-xL and Bcl-2 on apoptotic liver injury in transgenic mice

1999 ◽  
Vol 277 (3) ◽  
pp. G702-G708 ◽  
Author(s):  
Alix de la Coste ◽  
Monique Fabre ◽  
Nathalie McDonell ◽  
Arlette Porteu ◽  
Helène Gilgenkrantz ◽  
...  
Keyword(s):  
Liver Injury ◽  
Transgenic Mice ◽  
Fas Ligand ◽  
Dependent Manner ◽  
Protective Effects ◽  
Tnf Α ◽  
Apoptotic Pathways ◽  
Induced Apoptosis ◽  
Factor Α

Fas ligand (CD95L) and tumor necrosis factor-α (TNF-α) are pivotal inducers of hepatocyte apoptosis. Uncontrolled activation of these two systems is involved in several forms of liver injury. Although the broad antiapoptotic action of Bcl-2 and Bcl-xL has been clearly established in various apoptotic pathways, their ability to inhibit the Fas/CD95- and TNF-α-mediated apoptotic signal has remained controversial. We have demonstrated that the expression of BCL-2 in hepatocytes protects them against Fas-induced fulminant hepatitis in transgenic mice. The present study shows that transgenic mice overexpressing[Formula: see text]in hepatocytes are also protected from Fas-induced apoptosis in a dose-dependent manner. Bcl-xL and Bcl-2 were protective without any change in the level of endogenous[Formula: see text]or Bax and inhibited hepatic caspase-3-like activity. In vivo injection of TNF-α caused massive apoptosis and death only when transcription was inhibited. Under these conditions,[Formula: see text]mice were partially protected from liver injury and death but PK-BCL-2 mice were not. A similar differential protective effect of Bcl-xL and Bcl-2 transgenes was observed when Fas/CD95 was activated and transcription blocked. These results suggest that apoptosis triggered by activation of both Fas/CD95 and TNF-α receptors is to some extent counteracted by the transcription-dependent protective effects, which are essential for the antiapoptotic activity of Bcl-2 but not of Bcl-xL. Therefore, Bcl-xL and Bcl-2 appear to have different antiapoptotic effects in the liver whose characterization could facilitate their use to prevent the uncontrolled apoptosis of hepatocytes.

Deferasirox Inhibit Doxorubicin-Induced Reactive Oxygen Species Generation in Both Acute Myeloid Leukemia and Normal Heart Cell While Maintain the Cytotoxicity of Doxorubicin Only on Acute Myeloid Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3620-3620
Author(s):  
Su-Peng Yeh ◽  
Yu-Chien Chang ◽  
Wen-Jyi Lo ◽  
Min-Lih Huang ◽  
Yang-Sheng Yang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cell Line ◽  
Myeloid Leukemia ◽  
Heart Cell ◽  
Ros Generation ◽  
Heart Cells ◽  
Normal Heart ◽  
Intracellular Ros ◽  
Induced Apoptosis ◽  
Acute Myeloid

Abstract Abstract 3620 Background: Deferasirox (DFX) was recently found to have anti-leukemia effect both in vitro and in vivo. DFX can also potently inhibit the generation of intracellular reactive oxygen species (ROS). On the other hand, the generation of ROS by Doxorubicin (DOX) is critical for the cytotoxicity on both leukemia and normal heart cells. It is not known whether combining DFX and DOX will have synergistic or antagonizing effect on leukemic cells. Similarly, it is also unknown whether adding DFX to DOX will have protective effect on normal heart cell. Method: Cells of human acute myeloid leukemia (AML) cell line THP1, mice AML cell line WEHI3, and rat normal heart cell line H9C2 were treated with Doxorubicin 5microM for various duration in the presence of absence of DFX pretreatment (100microM for 10 minutes). Intracellular ROS generation was measured by the detection of 2,7-dichlorodihydrofluorescein (DCF) fluorescence intensity using flow cytometry. Apoptosis was determined by Annexin V-Propidium Iodide staining using flow cytometry. Cytotoxicity was determined by Trypan blue exclusion assay. Results: Although intracellular ROS was reduced, DFX alone induced apoptosis of THP1 (from 3% to 18%) and WEHI3 (from 31% to 49%) AML cells. DOX-induced ROS production was also significantly reduced when THP1, WEHI3, and H9C2 cells were pretreated with DFX (Figure 1a, 1b, 1c respectively). However, the DOX-induced apoptosis of THP1 and WEHI3 AML cells were not antagonized by DFX (Figure 2a). 24 hours after exposure to this physiological dose DOX, all the WEHI3 cells died in both DFX treated or untreated group (figure 2b). More importantly, DFX-pretreated H9C2 heart cells had fewer cell death (3.7%) after exposure to DOX (5microM for 24 hours) compared to non-DFX pretreated cells (8.5%). Conclusions: DFX alone induced apoptosis in two different AML cell lines. DFX also markedly reduced the ROS generation due to DOX treatment. However, DFX did not negatively influence the pro-apoptotic and cytotoxic effect of DOX on these AML cell lines. Interestingly, DFX also markedly reduced the DOX-induced ROS generation and DOX-induced cell death in normal rat heart cell, which might have protective effect on DOX-related cardiomyopathy. We are now using Balb/c-WEHI3 AML mice model to test whether DFX can protect cardiomyocytes from DOX-related damage while maintain the cytotoxic effect of DOX on AML cells. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Icariin Prevents H2O2-Induced Apoptosis via the PI3K/Akt Pathway in Rat Nucleus Pulposus Intervertebral Disc Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Xiangyu Deng ◽  
Sheng Chen ◽  
Dong Zheng ◽  
Zengwu Shao ◽  
Hang Liang ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Caspase 3 ◽  
Chinese Herb ◽  
Akt Pathway ◽  
Control Group ◽  
Protective Effects ◽  
Nucleus Pulposus Cells ◽  
Intracellular Ros ◽  
Induced Apoptosis

Icariin is a prenylated flavonol glycoside derived from the Chinese herb Epimedium sagittatum. This study investigated the mechanism by which icariin prevents H2O2-induced apoptosis in rat nucleus pulposus (NP) cells. NP cells were isolated from the rat intervertebral disc and they were divided into five groups after 3 passages: (A) blank control; (B) 200 μM H2O2; (C) 200 μM H2O2 + 20 μM icariin; (D) 20 μM icariin + 200 μM H2O2 + 25 μM LY294002; (E) 200 μM H2O2 + 25 μM LY294002. LY294002 is a selective inhibitor of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. NP cell viability, apoptosis rate, intracellular reactive oxygen species levels, and the expression of AKT, p-AKT, p53, Bcl-2, Bax, caspase-3 were estimated. The results show that, compared with the control group, H2O2 significantly increased NP cell apoptosis and the level of intracellular ROS. Icariin pretreatment significantly decreased H2O2-induced apoptosis and intracellular ROS and upregulated p-Akt and BCL-2 and downregulated caspase-3 and Bax. LY294002 abolished the protective effects of icariin. Our results show that icariin can attenuate H2O2-induced apoptosis in rat nucleus pulposus cells and PI3K/AKT pathway is at least partly included in this protection effect.

scholarly journals Antcin C fromAntrodia cinnamomeaProtects Liver Cells Against Free Radical-Induced Oxidative Stress and ApoptosisIn VitroandIn Vivothrough Nrf2-Dependent Mechanism

2013 ◽  
Vol 2013 ◽  
pp. 1-17 ◽  
Author(s):  
M. Gokila Vani ◽  
K. J. Senthil Kumar ◽  
Jiunn-Wang Liao ◽  
Shih-Chang Chien ◽  
Jeng-Leun Mau ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Transcriptional Activation ◽  
Liver Cells ◽  
Ros Generation ◽  
Antioxidant Genes ◽  
Pi3k Activation ◽  
Mice Liver ◽  
Induced Apoptosis

In this study, we investigated the cytoprotective effects of antcin C, a steroid-like compound isolated from Antrodia cinnamaomea against AAPH-induced oxidative stress and apoptosis in human hepatic HepG2 cells. Pretreatment with antcin C significantly protects hepatic cells from AAPH-induced cell death through the inhibition of ROS generation. Furthermore, AAPH-induced lipid peroxidation, ALT/AST secretion and GSH depletion was significantly inhibited by antcin C. The antioxidant potential of antcin C was correlated with induction of antioxidant genes including, HO-1, NQO-1,γ-GCLC, and SODviatranscriptional activation of Nrf2. The Nrf2 activation by antcin C is mediated by JNK1/2 and PI3K activation, whereas pharmacologic inhibition of JNK1/2 and PI3K abolished antcin C-induced Nrf2 activity. In addition, AAPH-induced apoptosis was significantly inhibited by antcin C through the down-regulation of pro-apoptotic factors including, Bax, cytochrome c, capase 9, -4, -12, -3, and PARP.In vivostudies also show that antcin C significantly protected mice liver from AAPH-induced hepatic injury as evidenced by reduction in hepatic enzymes in circulation. Further, immunocytochemistry analyses showed that antcin C significantly increased HO-1 and Nrf2 expression in mice liver tissues. These results strongly suggest that antcin C could protect liver cells from oxidative stress and cell deathviaNrf2/ARE activation.

scholarly journals Neutrophil Elastase Induces Chondrocyte Apoptosis and Facilitates the Occurrence of Osteoarthritis via Caspase Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Ganyu Wang ◽  
Weiqiang Jing ◽  
Yuxuan Bi ◽  
Yue Li ◽  
Liang Ma ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Neutrophil Elastase ◽  
Elderly Population ◽  
The Elderly ◽  
Chondrocyte Apoptosis ◽  
Intracellular Ros ◽  
Induced Apoptosis

Osteoarthritis (OA) is the most common and prevalent chronic joint disorders in the elderly population across the globe, resulting in severe disability and impairment of quality of life. Existing treatment can only alleviate the symptoms and delay the progression of OA. Therefore, novel and effective therapeutics strategies for OA need to be developed. Our present study first found that neutrophil elastase (NE) was significantly increased in OA patients’ synovial fluid. Next, we examined the effect of neutrophil elastase (NE) on chondrocytes in vitro and in vivo. The results showed that NE suppressed cell proliferation, induced apoptosis and prevented cell migration in chondrocytes in vitro, accompanied by the elevation of intracellular ROS and calcium level. Moreover, NE enhanced the cleaved caspase-3 levels and disrupted the mitochondrial transmembrane potential balance. Meanwhile, chondrocytes apoptosis induced by NE can be alleviated by caspase inhibitor, zVAD-FMK and antioxidants, GSH. Besides, treatment of sivelestat, the inhibitor of NE, significantly reduced the pathological processes in OA model rats in vivo. The results of our study suggested that NE is an important factor in OA, which induces chondrocyte apoptosis and facilitates the occurrence of OA via caspase signaling pathway, and targeting the crucial signal centering around NE may be the potential therapies for OA.

scholarly journals ROS-mediated inactivation of the PI3K/AKT pathway is involved in the antigastric cancer effects of thioredoxin reductase-1 inhibitor chaetocin

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Chuangyu Wen ◽  
Huihui Wang ◽  
Xiaobin Wu ◽  
Lu He ◽  
Qian Zhou ◽  
...  
Keyword(s):  
Critical Role ◽  
Thioredoxin Reductase ◽  
Akt Pathway ◽  
Ros Generation ◽  
In Vivo Models ◽  
M Phase ◽  
Tumorigenesis And Progression ◽  
Induced Apoptosis

Abstract Novel drugs are urgently needed for gastric cancer (GC) treatment. The thioredoxin-thioredoxin reductase (TRX-TRXR) system has been found to play a critical role in GC tumorigenesis and progression. Thus, agents that target the TRX-TRXR system may be highly efficacious as GC treatments. In this study, we showed that chaetocin, a natural product isolated from the Chaetomium species of fungi, inhibited proliferation, induced G2/M phase arrest and caspase-dependent apoptosis in both in vitro and in vivo models (cell xenografts and patient-derived xenografts) of GC. Chaetocin inactivated TRXR-1, resulting in the accumulation of reactive oxygen species (ROS) in GC cells; overexpression of TRX-1 as well as cotreatment of GC cells with the ROS scavenger N-acetyl-L-cysteine attenuated chaetocin-induced apoptosis; chaetocin-induced apoptosis was significantly increased when GC cells were cotreated with auranofin. Moreover, chaetocin was shown to inactivate the PI3K/AKT pathway by inducing ROS generation; AKT-1 overexpression also attenuated chaetocin-induced apoptosis. Taken together, these results reveal that chaetocin induces the excessive accumulation of ROS via inhibition of TRXR-1. This is followed by PI3K/AKT pathway inactivation, which ultimately inhibits proliferation and induces caspase-dependent apoptosis in GC cells. Chaetocin therefore may be a potential agent for GC treatment.

Crocin protects against beta-amyloid peptide-induced apoptosis in PC12 cells via PI3 K pathway

2020 ◽  
Vol 13 ◽  
Author(s):  
Reyhaneh Taheri ◽  
Elham Hadipour ◽  
Zahra Tayarani-Najaran
Keyword(s):  
Pc12 Cells ◽  
Caspase 3 ◽  
Beta Amyloid ◽  
Pi3 Kinase ◽  
Amyloid Peptide ◽  
Ros Generation ◽  
Protective Effects ◽  
Beta Amyloid Peptide ◽  
Cyt C ◽  
Induced Apoptosis

Background: Crocin is a known compound with antioxidant and anti-inflammatory property which many help to reduce the progression of neurological disorders. In this study, we aimed to investigate the protective effects of crocin on beta-amyloid peptide Aβ (1-40) and hydrogen peroxide (H2O2) induced neurotoxicity in PC12 cells. Methods: PC12 cells pretreated with crocin and donepezil (5 and 10 µM) for 2 h then treated with Aβ (1-40) (25 µM) for 24 h. In parallel after pretreatment with crocin (5 and 10 µM) and donepezil (5 and 10 µM) for 24 h, cells were treated with H2O2 (800 µM) for 4 h. Finally, the cell viability and intracellular reactive oxygen species (ROS) generation were evaluated using AlamarBlue® and 2', 7'-dichlorodihydrofluorescein diacetate (DCFH-DA), respectively. The western blot test was done to compare the protein level of phospho SAPK/JNK, SAPK/JNK, PI3 Kinase P85, Phospho-PI3 Kinase P85, caspase-3 and cytochrome c )cyt c). Results: Crocin and donepezil could significantly decrease the Aβ toxicity and ROS level. While treatment with Aβ increased Cyt c release from mitochondria to cytosol, cleaved form of caspase-3 (17 kDa) and activated form of SAPK/JNK p44/4 and decreased the activated form of PI3 Kinase P85 protein, crocin could significantly block the apoptosis initiated with Aβ. Conclusions: According to the results crocin could be a promising candidate for further evaluations against the development of Alzheimer's diseases through mitogen-activated protein kinases (MAPK) and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling (PI3 K/AKT) pathways.

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