scholarly journals Icariin Inhibits AGE-Induced Injury in PC12 Cells by Directly Targeting Apoptosis Regulator Bax

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Shao-Yang Zhao ◽  
Li-Xi Liao ◽  
Peng-Fei Tu ◽  
Wei-Wei Li ◽  
Ke-Wu Zeng
Keyword(s):  
Oxidative Stress ◽  
Pc12 Cells ◽  
Pc12 Cell ◽  
Cell Apoptosis ◽  
Diabetic Patients ◽  
Neuroprotective Effects ◽  
Apoptosis Pathway ◽  
Bax Protein ◽  
Pulldown Assay ◽  
And Migration

Diabetic encephalopathy (DE) is a serious complication caused by long-term cognitive impairment in diabetic patients. At present, there is no effective treatment for DE. Icariin (ICA) is a bioactive ingredient isolated from Epimedium. Previous research indicated that ICA was neuroprotective against Aβ-induced PC12 cell insult; however, the effect of ICA on an advanced glycosylation end product- (AGE-) induced neural injury model has not been studied. In this study, we investigated the neuroprotective effects of ICA on AGE-induced injury in PC12 cells. Our findings revealed that ICA could effectively protect PC12 cells from AGE-induced cell apoptosis by suppressing oxidative stress. Moreover, we observed that ICA could significantly protect against mitochondrial depolarization following AGE stimulation and inactivate the mitochondria-dependent caspase-9/3 apoptosis pathway. Most notably, we identified the direct target protein of ICA as apoptosis regulator Bax by a pulldown assay. We found that ICA could specifically target Bax protein and inhibit Bax dimer formation and migration to mitochondria. Furthermore, a siRNA knockdown experiment revealed that ICA could inhibit PC12 cell apoptosis and oxidative stress through targeting Bax. Taken together, our findings demonstrated that ICA could attenuate AGE-induced oxidative stress and mitochondrial apoptosis by specifically targeting Bax and further regulating the biological function of Bax on mitochondria.

Neuroprotective Effects of Extracts from the Radix Curcuma aromatica on H2O2-induced Damage in PC12 Cells

2018 ◽  
Vol 21 (8) ◽  
pp. 571-582 ◽  
Author(s):  
Juxiang Liu ◽  
Lianli Zhang ◽  
Dan Liu ◽  
Baocai Li ◽  
Mi Zhang
Keyword(s):  
Oxidative Stress ◽  
Pc12 Cells ◽  
Caspase 3 ◽  
Cell Damage ◽  
Positive Control ◽  
Neuroprotective Activity ◽  
Antioxidant Enzyme Activities ◽  
Morphologic Change ◽  
Neuroprotective Effects ◽  
Etoh Extract

Aim & Objectives: Curcuminoids are characteristic constituents in Curcuma, displaying obviously neuroprotective activities against oxidative stress. As one of the Traditional Chinese Medicines from Curcuma, the radix of Curcuma aromatica is also rich in those chemicals, but its neuroprotective activity and mechanism remain unknown. The aim of the current study is to evaluate the neuroprotective effects of extracts from the radix of C. aromatica (ECAs) on H2O2-damaged PC12 cells. Material and Methods: The model of oxidative stress damage was established by treatment of 400 µM H2O2 on PC12 to induce cell damage. After the treatment of ECWs for 24 h, the cell viability, LDH, SOD, CAT and GSH were measured to evaluate the neuroprotection of ECAs on that model. The potential action mechanism was studied by measurement of level of ROS, cell apoptosis rate, mitochondrial membrane potential (MMP), morphologic change, the intracellular Ca2+ content (F340/F380) and the expressions of Bcl-2, Bax and Caspase-3. Additionally, the constituents from tested extracts were analyzed by HPLC-DAD-Q-TOF-MS method. Results: Compared with a positive control, Vitamin E, 10 µg/ml of 95% EtOH extract (HCECA) and 75% EtOH extract (MCECA) can markedly increase the rate of cell survival and enhance the antioxidant enzyme activities of SOD, CAT, increase the levels of GSH, decrease LDH release and the level of ROS, attenuate the intracellular Ca2+ overloading, reduce the cell apoptotic rate and stabilize MMP, down-regulate Bcl-2 expression, up-regulate Bax and caspase-3 expression, and improve the change of cell morphology. The chemical analysis showed that diarylheptanoids and sesquiterpenoids are the major chemicals in tested extracts and the former were richer in HCECA and MCECA than others. Conclusions: These findings indicated that the effects of HCECA and MCECA on inhibiting the cells damage induced by H2O2 in PC12 are better than other extracts from the radix of C. aromatica, and the active constituents with neuroprotective effects consisting in those two active extracts are diarylheptanoids.

scholarly journals Artemisinin attenuated oxidative stress and apoptosis by inhibiting autophagy in MPP+-treated SH-SY5Y cells

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Junqiang Yan ◽  
Hongxia Ma ◽  
Xiaoyi Lai ◽  
Jiannan Wu ◽  
Anran Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Membrane Potential ◽  
Protein Expression ◽  
Mitochondrial Membrane Potential ◽  
Western Blotting ◽  
Cell Apoptosis ◽  
Mitochondrial Membrane ◽  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Neuroprotective Effects

Abstract Background Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. The oxidative stress is an important component of the pathogenesis of PD. Artemisinin (ART) has antioxidant and neuroprotective effects. The purpose of this study is to explore the neuroprotective effect of ART on 1-methyl-4-phenyliodine iodide (MPP +)-treated SH-SY5Y cells and underlying mechanism. Methods We used MPP+-treated SH-SY5Y cells to study the neuroprotective effect of ART. Cell viability was measured by MTT assay after incubating the cells with MPP+ and/or ART for 24 h. DCFH-DA was used to detect the level of intracellular reactive oxygen species (ROS), and WST-8 was used to detect the level of superoxide dismutase (SOD). The level of intracellular reduced glutathione (GSH) was detected with 5,5΄-dithiobis-(2-nitrobenzoic acid), and the level of malondialdehyde (MDA) was assessed based on the reaction of MDA and thiobarbituric acid. A mitochondrial membrane potential detection kit (JC-1) was used to detect changes in the mitochondrial membrane potential (MMP), and an Annexin V-FITC cell apoptosis kit was used to detect cell apoptosis. The expression levels of caspase-3, cleaved caspase-3 and the autophagy-related proteins LC3, beclin-1, and p62 were detected by Western blotting. In addition, to verify the change in autophagy, we used immunofluorescence to detect the expression of LC3 and p62. Results No significant cytotoxicity was observed at ART concentrations up to 40 μM. ART could significantly increase the viability of SH-SY5Y cells treated with MPP+ and reduce oxidative stress damage and apoptosis. In addition, the Western blotting and immunofluorescence results showed that MPP+ treatment could increase the protein expression of beclin1 and LC3II/LC3I and decrease the protein expression of p62, indicating that MPP+ treatment could induce autophagy. Simultaneous treatment with ART and MPP+ could decrease the protein expression of beclin1 and LC3II/LC3I and increase the protein expression of p62, indicating that ART could decrease the level of autophagy induced by MPP+. Conclusion Our results indicate that ART has a protective effect on MPP+-treated SH-SY5Y cells by the antioxidant, antiapoptotic activities and inhibition of autophagy. Our findings may provide new hope for the prevention and treatment of PD.

scholarly journals Natural compounds attenuate heavy metal-induced PC12 cell damage

2020 ◽  
Vol 48 (6) ◽  
pp. 030006052093084
Author(s):  
Lina Yang ◽  
Keshu Shen ◽  
Dongping Ji
Keyword(s):  
Heavy Metal ◽  
Pc12 Cells ◽  
Pc12 Cell ◽  
Therapeutic Potential ◽  
Cell Damage ◽  
Mitochondrial Protein ◽  
Natural Compounds ◽  
Alpha Tocopherol ◽  
Neuroprotective Effects

Objectives To investigate the neuroprotective effects of six natural compounds (caffeine, gallic acid, resveratrol, epigallocatechin gallate [EGCG], L-ascorbic acid and alpha tocopherol [Vitamin E] on heavy metal-induced cell damage in rat PC12 cells. Methods In this in vitro experiment, rat PC12 cells were exposed to four heavy metals (CdCl2, HgCl2, CoCl2 and PbCl2) at different concentrations and cell apoptosis, necrosis and oxidative stress were assessed with and without the addition of the six natural compounds. Results The metals decreased cell viability but the natural compounds attenuated their effects on apoptosis, necrosis and reactive oxygen species (ROS) levels. Mitochondrial protein changes were involved in the regulation. Conclusion Overall, the natural compounds did provide protection against the metal-induced PC12 cell damage. These data suggest that natural compounds may have therapeutic potential against metal-induced neurodegenerative disease.

scholarly journals Amarogentin from Gentiana rigescens Franch Exhibits Antiaging and Neuroprotective Effects through Antioxidative Stress

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Dejene Disasa ◽  
Lihong Cheng ◽  
Majid Manzoor ◽  
Qian Liu ◽  
Ying Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Antioxidant Activity ◽  
Natural Products ◽  
Survival Rate ◽  
Pc12 Cells ◽  
Neuroprotective Effects ◽  
Replicative Lifespan ◽  
Antioxidative Stress ◽  
Gentiana Rigescens

In the present study, the replicative lifespan assay of yeast was used to guide the isolation of antiaging substance from Gentiana rigescens Franch, a traditional Chinese medicine. A compound with antiaging effect was isolated, and the chemical structure of this molecule as amarogentin was identified by spectral analysis and compared with the reported data. It significantly extended the replicative lifespan of K6001 yeast at doses of 1, 3, and 10 μM. Furthermore, amarogentin improved the survival rate of yeast under oxidative stress by increasing the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx), and these enzymes’ gene expression. In addition, this compound did not extend the replicative lifespan of sod1, sod2, uth1, and skn7 mutants with K6001 background. These results suggested that amarogentin exhibited antiaging effect on yeast via increase of SOD2, CAT, GPx gene expression, enzyme activity, and antioxidative stress. Moreover, we evaluated antioxidant activity of this natural products using PC12 cell system, a useful model for studying the nervous system at the cellular level. Amarogentin significantly improved the survival rate of PC12 cells under H2O2-induced oxidative stress and increased the activities of SOD and SOD2, and gene expression of SOD2, CAT, GPx, Nrf2, and Bcl-x1. Meanwhile, the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) of PC12 cells were significantly reduced after treatment of the amarogentin. These results indicated that antioxidative stress play an important role for antiaging and neuroprotection of amarogentin. Interestingly, amarogentin exhibited neuritogenic activity in PC12 cells. Therefore, the natural products, amarogentin from G. rigescens with antioxidant activity could be a good candidate molecule to develop drug for treating neurodegenerative diseases.

scholarly journals A combination of curcumin, vorinostat and silibinin reverses Aβ-induced nerve cell toxicity via activation of AKT-MDM2-p53 pathway

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6716 ◽  
Author(s):  
Jia Meng ◽  
Yan Li ◽  
Mingming Zhang ◽  
Wenjing Li ◽  
Lin Zhou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pc12 Cells ◽  
Nerve Cell ◽  
Drug Combination ◽  
Therapeutic Option ◽  
Oxidative Stress Marker ◽  
Cell Toxicity ◽  
Neuroprotective Effects ◽  
Cell Viability Assay ◽  
P53 Pathway

Alzheimer’s disease (AD) is a significant health issue for the elderly and becoming increasingly common as the global population ages. Although many efforts have been made to elucidate its pathology, there is still a lack of effective clinical anti-AD agents. Previous research has shown the neuroprotective properties of a combination of curcumin and vorinostat. In this study, nine other neuroprotective agents were investigated to examine whether a three-drug combination of curcumin, vorinostat, and a new drug is more advantageous than the previous two-drug combination in alleviating amyloid beta (Aβ)-induced nerve cell toxicity. Cell viability assay was performed to screen these agents, and further validation tests, including determination of cellular oxidative stress, apoptosis, and activity of the AKT/MDM2/p53 pathway, were performed. Among the nine candidate compounds, only silibinin at 1 µM reduced Aβ25–35-induced toxicity in PC12 cells. The neuroprotective effects of 1 µM silibinin in combination with 5 µM curcumin and 0.5 µM vorinostat (CVS) was shown in PC12 cells, in which it decreased apoptosis and oxidative stress marker levels that were increased by 20 µM Aβ25–35. Western blotting results showed that CVS pretreatment significantly increased the phosphorylation of AKT, BAD, and MDM2, which resulted in decreased intracellular expression of p53. Further, immunofluorescence results showed reduced p53 levels in the nuclei of PC12 cells following CVS pretreatment, indicating a reduction in the p53-mediated transcriptional activity associated with Aβ25–35 exposure. In conclusion, our findings suggested that pretreatment with CVS protected PC12 cells from Aβ25–35-induced toxicity through modulation of the AKT/MDM2/p53 pathway. Thus, CVS may present a new therapeutic option for treating AD.

scholarly journals Fraxinellone Has Anticancer Activity by Inducing Osteosarcoma Cell Apoptosis via Promoting Excessive Autophagy Flux

2021 ◽  
Vol 12 ◽  
Author(s):  
Bin He ◽  
Wenkan Zhang ◽  
Jiaming He
Keyword(s):  
Cell Apoptosis ◽  
Early Stage ◽  
Osteosarcoma Cell ◽  
Dependent Manner ◽  
Orthotopic Model ◽  
Autophagy Flux ◽  
Neuroprotective Effects ◽  
Anti Cancer ◽  
And Migration

Osteosarcoma is a malignant bone tumor that is easy to metastasize in the early stage and has a very poor prognosis. Fraxinellone (FRA) is one of the main components isolated from the D. dasycarpus plant. Its anti-inflammatory and neuroprotective effects have been confirmed, but the research on the anti-cancer effect of FRA and its potential mechanism is relatively scarce. In this study, we found that FRA inhibited the proliferation and migration of osteosarcoma cells HOS and MG63 in a dose-dependent manner. Immunofluorescence, fluorescence staining and western blotting analysis showed that FRA could simultaneously induce osteosarcoma cell apoptosis and increase autophagy flux. Subsequent turnaround experiments suggested that the pro-apoptotic effect of FRA was achieved through excessive autophagy flux. The results of the xenograft orthotopic model further supported the anti-cancer effects of FRA, indicating that FRA treatment inhibited the growth of osteosarcoma, and the pro-apoptotic and autophagy effects of FRA were also proved in vivo. These studies provide new ideas for the future treatment of osteosarcoma and offer theoretical support for the anti-cancer mechanism of FRA.

Protective effect of nitronyl nitroxide against hypoxia-induced damage in PC12 cells

2020 ◽  
Vol 98 (3) ◽  
pp. 345-353 ◽  
Author(s):  
Hongbo Luo ◽  
Wei Sun ◽  
Jin Shao ◽  
Huiping Ma ◽  
Zhengping Jia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pc12 Cells ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Morphological Changes ◽  
Radical Scavenging ◽  
Protective Effects ◽  
Nitronyl Nitroxide ◽  
Promising Candidate ◽  
Radical Scavenging Properties

Hypoxia induces cellular oxidative stress that is associated with neurodegenerative diseases. HPN (4′-hydroxyl-2-substituted phenyl nitronyl nitroxide), a stable nitronyl nitroxide, has excellent free radical scavenging properties. The purpose of this study was to investigate the protective effects of HPN on hypoxia-induced damage in PC12 cells. It was shown that HPN significantly attenuated hypoxia-induced loss of cell viability, release of lactate dehydrogenase (LDH), and morphological changes in PC12 cells. Moreover, hypoxic PC12 cells had increased levels of reactive oxygen species (ROS), malondialdehyde (MDA), and expression of HIF-1α and VEGF, but had reduced levels of superoxide dismutase (SOD) and catalase (CAT), and HPN reversed these changes. HPN also inhibited hypoxia-induced cell apoptosis via suppressing the expression of Bax, cytochrome c, and caspase-3, and inducing the expression of Bcl-2. These results indicate that the protective effects of HPN on hypoxia-induced damage in PC12 cells is associated with the suppression of hypoxia-induced oxidative stress and cell apoptosis. HPN could be a promising candidate for the development of a novel neuroprotective agent.

scholarly journals P90RSK and Nrf2 Activation via MEK1/2-ERK1/2 Pathways Mediated by Notoginsenoside R2 to Prevent 6-Hydroxydopamine-Induced Apoptotic Death in SH-SY5Y Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Xiang-Bao Meng ◽  
Gui-Bo Sun ◽  
Min Wang ◽  
Jing Sun ◽  
Meng Qin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Panax Notoginseng ◽  
Neuroprotective Effects ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Downstream Target ◽  
Nrf2 Activation ◽  
Mitochondrial Membrane Depolarization ◽  
Activity Enhancement ◽  
6 Hydroxydopamine

6-Hydroxydopamine (6-OHDA) is known to contribute to neuronal death in Parkinson's disease. In this study, we found that the preincubation of SH-SY5Y cells for 24 h with 20 μM notoginsenoside R2 (NGR2), which is a newly isolated notoginsenoside fromPanax notoginseng, showed neuroprotective effects against 6-OHDA-induced oxidative stress and apoptosis. NGR2 incubation successively resulted in the activation of P90RSK, inactivation of BAD, and inhibition of 6-OHDA-induced mitochondrial membrane depolarization, thus preventing the mitochondrial apoptosis pathway. NGR2 incubation also led to the activation of Nrf2 and subsequent activity enhancement of phase II detoxifying enzymes, thus suppressing 6-OHDA-induced oxidative stress, and these effects could be removed by Nrf2 siRNA. We also found that the upstream activators of P90RSK and Nrf2 were the MEK1/2–ERK1/2 pathways but not the JNK, P38, or PI3K/Akt pathways. Interestingly, NGR2 incubation could also activate MEK1/2 and ERK1/2. Most importantly, NGR2-mediated P90RSK and Nrf2 activation, respective downstream target activation, and neuroprotection were reversed by the genetic silencing of MEK1/2 and ERK1/2 by using siRNA and PD98059 application. These results suggested that the neuroprotection elicited by NGR2 against 6-OHDA-induced neurotoxicity was associated with NGR2-mediated P90RSK and Nrf2 activation through MEK1/2-ERK1/2 pathways.

Neuroprotective Effects of SG-168 Against Oxidative Stress-Induced Apoptosis in PC12 Cells

2011 ◽  
Vol 14 (1-2) ◽  
pp. 120-127 ◽  
Author(s):  
Mi-Young Yoon ◽  
Ji-Hwan Hwang ◽  
Jae-Hee Park ◽  
Mi-Ra Lee ◽  
Hyun-Jung Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pc12 Cells ◽  
Neuroprotective Effects ◽  
Induced Apoptosis

scholarly journals Apoptotic Inducement of Neuronal Cells by Aluminium Chloride and the Neuroprotective Effect of Eugenol in Wistar Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Samuel Bolaji Mesole ◽  
Okpanachi Omachonu Alfred ◽  
Uthman Ademola Yusuf ◽  
Lwiindi Lukubi ◽  
Dailesi Ndhlovu
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Wistar Rats ◽  
Caspase 3 ◽  
Anaesthetic Agent ◽  
Neuroprotective Effect ◽  
Aluminium Chloride ◽  
Neuroprotective Effects ◽  
Stress Markers ◽  
Bax Protein

Aluminium is known to accelerate oxidative stress, amyloid beta (Aβ) deposition, and plaque formation in the brain of rats. Objective. The present study is aimed at studying the neuroprotective effects of eugenol following aluminium-induced neurotoxicity on caspase-3, apoptotic proteins (Bcl-2 and Bax), and oxidative stress markers in Wistar rats such as superoxide dismutase (SOD), glutathione peroxidase (GPx), nitric oxide (NO), and assay oxidative stress to mitochondrial DNA (mtDNA) by measuring the levels of 8-hydroxy-2-deoxyguanosine (8-OHdG). Materials and methods. Twenty (20) adult Wistar rats were randomly divided into four (4) groups with five animals in each group. Route of administration was oral throughout the duration of this study and this study lasted for 21 days. Rats were sacrificed 24 hours after administration of the last dose (i.e., day 22) with 0.8 mg/kg ketamine as an anaesthetic agent. Results. Exposure to AlCl3 resulted in a significant (p<0.01) elevation in the levels of nitric oxide and 8-hydroxy-2-deoxyguanosine (8-OHdG), enhanced the activity of caspase-3, increased the level of proapoptotic protein Bax and reduced the levels of antiapoptotic protein Bcl-2, and significantly (p<0.01) reduced the levels of SOD and GPx. However, treatment with eugenol resulted in a significant reduction (p<0.01) in the levels of nitric oxide (NO) and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, inhibited the activity of caspase-3, increased levels of Bcl-2 and significantly (p<0.05) reduced levels of Bax protein, respectively, and also significantly (p<0.05) increased the levels of SOD and GPx. Our results would hereby suggest that eugenol would provide a therapeutic value against aluminium-induced oxidative stress as related to antioxidant and antiapoptotic activities.

Sign in / Sign up

Export Citation Format

Share Document