scholarly journals Protective Activity of Aspirin Eugenol Ester on Paraquat-Induced Cell Damage in SH-SY5Y Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Zhen-Dong Zhang ◽  
Ya-Jun Yang ◽  
Zhe Qin ◽  
Xi-Wang Liu ◽  
Shi-Hong Li ◽  
...  

Aspirin eugenol ester (AEE) is a new pharmaceutical compound esterified by aspirin and eugenol, which has anti-inflammatory, antioxidant, and other pharmacological activities. The aim of this study was to investigate the protective effect of AEE on paraquat- (PQ-) induced cell damage of SH-SY5Y human neuroblastoma cells and its potential molecular mechanism. There was no significant change in cell viability when AEE was used alone. PQ treatment reduced cell viability in a concentration-dependent manner. However, AEE reduced the PQ-induced loss of cell viability. Flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and 4 ′ 6-diamidino-2-phenylindole (DAPI) staining were used to evaluate cell apoptosis. Compared with the PQ group, AEE pretreatment could significantly inhibit PQ-induced cell damage. AEE pretreatment could reduce the cell damage of SH-SY5Y cells induced by PQ via reducing superoxide anion, intracellular reactive oxygen species (ROS), and mitochondrial ROS (mtROS) and increasing the levels of mitochondrial membrane potential ( Δ Ψ m ). At the same time, AEE could increase the activity of glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) and decrease the activity of malondialdehyde (MDA). The results showed that compared with the control group, the expression of p-PI3K, p-Akt, and Bcl-2 was significantly decreased, while the expression of caspase-3 and Bax was significantly increased in the PQ group. In the AEE group, AEE pretreatment could upregulate the expression of p-PI3K, p-Akt, and Bcl-2 and downregulate the expression of caspase-3 and Bax in SH-SY5Y cells. PI3K inhibitor LY294002 and the silencing of PI3K by shRNA could weaken the protective effect of AEE on PQ-induced SH-SY5Y cells. Therefore, AEE has a protective effect on PQ-induced SH-SY5Y cells by regulating the PI3K/Akt signal pathway to inhibit oxidative stress.

Reproduction ◽  
2014 ◽  
Vol 147 (3) ◽  
pp. 301-311 ◽  
Author(s):  
M A Costa ◽  
B M Fonseca ◽  
E Keating ◽  
N A Teixeira ◽  
G Correia-da-Silva

The major endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG) is a member of the endocannabinoid system (ECS) that participates in cell proliferation and apoptosis, important events for the homoeostasis of biological systems. The formation of placenta is one of the most important stages of pregnancy and its development requires highly regulated proliferation, differentiation and apoptosis of trophoblasts. Anomalies in these processes are associated with gestational pathologies. In this work, we aimed to study the involvement of 2-AG in cytotrophoblast cell turnover. We found that 2-AG biosynthetic (diacylglycerol lipase A) and degradative (monoacylglycerol lipase) enzymes are expressed in human cytotrophoblasts and in BeWo cells. We also found that 2-AG induces a decrease in cell viability in a time- and concentration-dependent manner and exerts antiproliferative effects. The loss of cell viability induced by a 48-h treatment with 2-AG (10 μM) was accompanied by chromatin fragmentation and condensation, morphological features of apoptosis. Additionally, 2-AG induced an increase in caspase 3/7 and 9 activities, a loss of mitochondrial membrane potential (Δψm) and an increase in reactive oxygen species (ROS)/reactive nitrogen species (RNS) generation, suggesting the activation of the mitochondrial pathway. Moreover, whereas Δψm loss and ROS/RNS generation were significantly attenuated by the antagonists of both the cannabinoid receptors 1 and 2 (CB1 and CB2), the increase in caspase 3/7 and 9 activities and loss of cell viability were reversed only by the antagonist of CB2 receptor; the blockage of the eCB membrane transporter and the depletion of cholesterol failed to reverse the effects of 2-AG. Therefore, this work supports the importance of cannabinoid signalling during cytotrophoblast cell turnover and that its deregulation may be responsible for altered placental development and poor pregnancy outcomes.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Zhen-Dong Zhang ◽  
Ya-Jun Yang ◽  
Xi-Wang Liu ◽  
Zhe Qin ◽  
Shi-Hong Li ◽  
...  

Aspirin eugenol ester (AEE) is a new pharmaceutical compound esterified by aspirin and eugenol, which has anti-inflammatory, antioxidant, and other pharmacological activities. This study is aimed at identifying the protective effect of AEE against H2O2-induced apoptosis in rat adrenal pheochromocytoma PC12 cells and the possible mechanisms. The results of cell viability assay showed that AEE could increase the viability of PC12 cells stimulated by H2O2, while AEE alone had no significant effect on the viability of PC12 cells. Compared with the control group, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were significantly decreased, and the content of malondialdehyde (MDA) was significantly increased in the H2O2 group. By AEE pretreatment, the level of MDA was reduced and the levels of SOD, CAT, and GSH-Px were increased in H2O2-stimulated PC12 cells. In addition, AEE could reduce the apoptosis of PC12 cells induced by H2O2 via reducing superoxide anion, intracellular ROS, and mitochondrial ROS (mtROS) and increasing the levels of mitochondrial membrane potential (ΔΨm). Furthermore, the results of western blotting showed that compared with the control group, the expression of p-PI3K, p-Akt, and Bcl-2 was significantly decreased, while the expression of Caspase-3 and Bax was significantly increased in the H2O2 group. In the AEE group, AEE pretreatment could upregulate the expression of p-PI3K, p-Akt, and Bcl-2 and downregulate the expression of Caspase-3 and Bax in PC12 cells stimulated with H2O2. The silencing of PI3K with shRNA and its inhibitor-LY294002 could abrogate the protective effect of AEE in PC12 cells. Therefore, AEE has a protective effect on H2O2-induced PC12 cells by regulating the PI3K/Akt signal pathway to inhibit oxidative stress.


2020 ◽  
Author(s):  
K. Zerrouki ◽  
N. Djebli ◽  
L. Gadouche ◽  
I. Erdogan Orhan ◽  
F. SezerSenol Deniz ◽  
...  

Nowadays, because of the industrialization, a lot of contaminant were available ; the consequences of this availability are apparition of diseases including neurodegeneration. Neurodegenerative diseases of the human brain comprise a variety of disorders that affect an increasing percentage of the population. This study is based on the effect of the Boswellic resin, which is from a medicinal plant and known for its antioxidant effects on nerve cell damage. The objective of this work was to evaluate the in vitro and in vivo effects of the Boswellic resin on anticholinesterase activity and Alzheimer’s disease (AD) induced by D-galactose and aluminum tetrachloride in Swiss mice. Chemical composition of the resin essential oil was identified by the CG-MS analysis. The antioxidant activity was also assessed by the DMPD and metal chelation methods. In order to understand the mechanism of memory improvement, the acetylcholinesterase, AChE, and butyrylcholinesterase, BChE, inhibitory assays were performed. In vivo part of the study was achieved on Swiss mice divided into four groups: control, AD model, treated AD, and treated control group. The identification of chemical composition by CG-MS reach the 89.67% of the total extract compounds presented some very important molecules (p-Cymene, n-Octyl acetate, α-Pinene…). The present study proves that Boswellic resin improves memory and learning in treated Alzheimer’s group, modulates the oxidative stress and be involved in the protective effect against amyloid deposition and neurodegeneration, and stimulates the immune system in mice’s brain.


2019 ◽  
Vol 19 (9) ◽  
pp. 673-682 ◽  
Author(s):  
Panpan Chang ◽  
Yuzi Tian ◽  
Aaron M. Williams ◽  
Umar F. Bhatti ◽  
Baoling Liu ◽  
...  

Background: Histone deacetylase (HDAC) 6 inhibitors have demonstrated significant protective effects in traumatic injuries. However, their roles in neuroprotection and underlying mechanisms are poorly understood. This study sought to investigate the neuroprotective effects of Tubastatin A (Tub-A), an HDAC6 inhibitor, during oxygenglucose deprivation (OGD) in HT22 hippocampal cells. Methods: HT22 hippocampal cells were exposed to OGD. Cell viability and cytotoxicity were assessed by cell counting kit-8 (CCK-8) and lactate dehydrogenase (LDH) release assay. Cellular apoptosis was assessed by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Mitochondria membrane potential was detected using JC-1 dye. Expressions of acetylated α-tubulin, α-tubulin, cytochrome c, VDAC, Bax, Bcl- 2, cleaved caspase 3, phosphorylated Akt, Akt, phosphorylated GSK3β and GSK3β were analyzed by Western blot analysis. Results: Tub-A induced acetylation of α-tubulin, demonstrating appropriate efficacy. Tub-A significantly increased cell viability and attenuated LDH release after exposure to OGD. Furthermore, Tub-A treatment blunted the increase in TUNEL-positive cells following OGD and preserved the mitochondrial membrane potential. Tub-A also attenuated the release of cytochrome c from the mitochondria into the cytoplasm and suppressed the ratio of Bax/Bcl-2 and cleaved caspase 3. This was mediated, in part, by the increased phosphorylation of Akt and GSK3β signaling pathways. Conclusion: HDAC 6 inhibition, using Tub-A, protects against OGD-induced injury in HT22 cells by modulating Akt/GSK3β signaling and inhibiting mitochondria-mediated apoptosis.


Author(s):  
Kartika Arum Wardani ◽  
Kholida Nur Aini ◽  
Heny Arwati ◽  
Willy Sandhika

Abstract Sequestration of Plasmodium berghei ANKA-infected erythrocytes occurs in BALB/c mice as characteristic of  Plasmodium falciparum infection in humans. Animals’ bile has been widely used for centuries in Traditional Chinese Medicine. Goat bile has been used in healing infectious and non-infectious diseases; however, no report on the use of goat bile against malaria infection and sequestration. The purpose of this study was to analyze the correlation between parasitemia and sequestration in the liver of P.berghei ANKA-infected BALB/c mice treated with goat bile. This research was an in vivo experimental study using the post-test control group design. The male BALB/c mice aged ± 6 weeks, body weight 20-25 g were used. The mice were divided into five groups where Group 1-3 were mice treated with goat bile 25%, 50%, and 100%, respectively. Group 4-5 were negative (sterile water) and positive controls (DHP). Parasitemia was observed daily from each mouse and the number of sequestered infected erythrocytes on the endothelium of sinusoids. The data were analyzed using t independent test. Antimalarial activity of goat bile was shown by the lower parasitemia in goat bile-treated mice compared with the negative control. The average number of sequestration was goat bile concentration-dependent manner. The higher the concentration, the lower the number of sequestration. Sequestration was correlated with parasitemia (p=0,0001). Sequestration of P.berghei ANKA-infected erythrocytes correlated with parasitemia, and was goat bile concentration-dependent manner. Keywords: Malaria, parasitemia, sequestration, goat bileCorrespondence: [email protected]


2021 ◽  
Author(s):  
Yan Zhang ◽  
Linchao Zhang ◽  
JiaLu Bao ◽  
LianTao Liu ◽  
Xiaodan Wang

Abstract To investigate the mechanism perfluorooctanoic acid (PFOA)’s toxicity on the uterus and liver of the mice during early pregnancy, pregnant mice were given 0, 1, 5, 10, 20, 40 mg/kg PFOA daily by gavage from gestational day (GD) 1-7, and sacrificed on GD 9. Uterus and liver weight were recorded, liver and uterine indexes were calculated, histopathological changes of the liver and uterus were examined, and levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) in liver were detected by spectrophotometric method. Expression of FAS, FASL, Bax, Bcl-2, and Caspase-3 in decidual cells were detected by immunohistochemistry and the TUNEL method was used to detect apoptotic uterine cells. Results showed that liver weight increased, and the uterus index was significantly reduced at 40 mg/kg compared with the control group. With increasing doses of PFOA, levels of SOD and GSH-PX were significantly decreased, and MDA significantly increased in liver tissue. 20 mg/kg and 40 mg/kg of PFOA caused greater harm to the uterus and congestion and resorption may occur. Expression of FAS, FASL, Bax, and Caspase-3 in decidual cells of the uterus in PFOA treatment groups significantly increased in a dose-dependent manner. The expression of Bcl-2 was down-regulated, which decreased the ratio of Bcl-2/Bax. It is therefore proposed that oxidative damage may be one of the mechanisms by which PFOA induces liver toxicity, and a subsequent increase in uterine cell apoptosis may induce embryo loss or damage.


Author(s):  
Elham Hoveizi ◽  
Fatemeh Fakharzadeh Jahromi

Background: The development of effective anticancer drugs is a significant health issue. Previous studies showed that members of the benzimidazole family have anticancer effects on several cancers Objectives: The present study investigated the cytotoxic effect of flubendazole on A549 human lung cancer cells. Methods: The A549 cells were treated with flubendazole at 1, 2, 5, and 10 µM concentrations for three days. Cell viability was measured by the MTT assay and Acridine orange staining. Also, the expressions of P62 and Beclin -1 were analyzed by qRT-PCR analysis. Results: Cell viability of A549 cells, in a concentration-dependent manner, showed significant differences between the treatment and control groups, and the IC50 value was determined to be 2 µM. Also, flubendazole reduced the expression of P62 and increased the expression of Beclin 1 in treated cells. Conclusions: Flubendazole induces cell death in A549 cells in a dose and time-dependent manner and can offer new factors in lung cancer therapeutic strategies.


2020 ◽  
Vol 10 (1) ◽  
pp. 61-67
Author(s):  
Hassan Sadraei ◽  
Sabihe Tabesh

Introduction: Quercetin is a flavonoid compound found in many medicinal plants. Antispasmodic effect of quercetin has been reported in ileum and uterus smooth muscles but not in bladder. Therefore, the objective of this research was to investigate relaxant effect of quercetin in rabbit isolated bladder. Methods: Male rabbit was asphyxiated with carbon dioxide and then sacrificed. The whole bladder was dissected out and placed in oxygenated Tyrode’s solution. Isolated bladder was cut into longitudinal strips and placed in an organ bath for contraction studies. Contractions were induced with KCl (20mM), acetylcholine (5μM) and electrical field stimulation (EFS). Full inhibitory concentration–response curve was constructed for quercetin following addition of above spasmogens. Quercetin was added into the organ bath with 2 fold increments in concentration until maximum response was achieved. Nifedipine was used as positive control group and equivalent volume of quercetin vehicle (water + DMSO) was used as negative control group.Results: Quercetin (4 μg/mL to 640 μg/mL) in a concentration dependent manner inhibited isolated bladder strips contracted by KCl (IC50=159±25 μg/mL), acetylcholine (IC50=43±9.1 μg/mL) and EFS (IC50=38±9.3 μg/mL). In the highest used concentration, quercetin completely removed contractile responses to KCl, acetylcholine and electrical filed stimulation (EFS). Nifedipine totally inhibited KCl response (IC50=115±36 ng/mL) but only partially inhibited acetylcholine and EFS responses. Conclusion: These results confirm the relaxant effect of quercetin on rabbit bladder and if similar effects are seen in human studies, then quercetin would be a suitable drug candidate to be investigated for bladder incontinence.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Prisca Bustamante Alvarez ◽  
Alexander Laskaris ◽  
Alicia A. Goyeneche ◽  
Yunxi Chen ◽  
Carlos M. Telleria ◽  
...  

Abstract Background Uveal melanoma (UM), the most prevalent intraocular tumor in adults, is a highly metastatic and drug resistant lesion. Recent studies have demonstrated cytotoxic and anti-metastatic effects of the antiprogestin and antiglucocorticoid mifepristone (MF) in vitro and in clinical trials involving meningioma, colon, breast, and ovarian cancers. Drug repurposing is a cost-effective approach to bring approved drugs with good safety profiles to the clinic. This current study assessed the cytotoxic effects of MF in human UM cell lines of different genetic backgrounds. Methods The effects of incremental concentrations of MF (0, 5, 10, 20, or 40 μM) on a panel of human UM primary (MEL270, 92.1, MP41, and MP46) and metastatic (OMM2.5) cells were evaluated. Cells were incubated with MF for up to 72 h before subsequent assays were conducted. Cellular functionality and viability were assessed by Cell Counting Kit-8, trypan blue exclusion assay, and quantitative label-free IncuCyte live-cell analysis. Cell death was analyzed by binding of Annexin V-FITC and/or PI, caspase-3/7 activity, and DNA fragmentation. Additionally, the release of cell-free DNA was assessed by droplet digital PCR, while the expression of progesterone and glucocorticoid receptors was determined by quantitative real-time reverse transcriptase PCR. Results MF treatment reduced cellular proliferation and viability of all UM cell lines studied in a concentration-dependent manner. A reduction in cell growth was observed at lower concentrations of MF, with evidence of cell death at higher concentrations. A significant increase in Annexin V-FITC and PI double positive cells, caspase-3/7 activity, DNA fragmentation, and cell-free DNA release suggests potent cytotoxicity of MF. None of the tested human UM cells expressed the classical progesterone receptor in the absence or presence of MF treatment, suggesting a mechanism independent of the modulation of the cognate nuclear progesterone receptor. In turn, all cells expressed non-classical progesterone receptors and the glucocorticoid receptor. Conclusion This study demonstrates that MF impedes the proliferation of UM cells in a concentration-dependent manner. We report that MF treatment at lower concentrations results in cell growth arrest, while increasing the concentration leads to lethality. MF, which has a good safety profile, could be a reliable adjuvant of a repurposing therapy against UM.


Author(s):  
Berenice Aranda-Cuevas ◽  
Jorge Tamayo- Cortez ◽  
Lourdes Vargas y Vargas ◽  
Ignacio Islas- Flores ◽  
Víctor Arana- Argáez ◽  
...  

The present study evaluates the immunomodulatory effect of high molecular weight fractions of Aloe vera polysaccharides harvested during the dry season (March-April) and the rainy season (August-September). Peritoneal macrophages (MΦs) secluded from Balb/c mice underwent treatment with A. vera leaves extract and acemannan standard (the major component found in A. vera) and stimulated with lipopolysaccharides (LPS). Macrophage cell viability was assessed by the 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide method. Phagocytic activity was also evaluated in peritoneal macrophages, such as the production of nitric oxide and interleukin 6 (IL-6). In the results, found that the A. vera polysaccharides harvested during the rainy season stimulated the phagocytic activity with greater intensity than dry season and improvement NO and IL-6 production. No cytotoxic effect was found on cell viability and they cause a significant proliferative effect on macrophages in a concentration-dependent manner. It can be concluded that the A. vera polysaccharides harvested during the rainy season possessed a stronger immunostimulatory effect compared to the extracts from leaves obtained during dry seasons in a concentration-dependent manner without aff at the cell viability of macrophages.


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