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.

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 Shenmai Injection Exerts Neuroprotective Functions by Down-regulating MicroRNA-19a in H 2 O 2 -induced PC12 Cells

2022 ◽  
Author(s):  
Jing Wu ◽  
zhonghao li ◽  
xiaoke dong ◽  
siyuan yuan ◽  
jinmin liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Western Blot ◽  
Pc12 Cells ◽  
Ischemia Reperfusion ◽  
Reperfusion Therapy ◽  
Pathological Process ◽  
Cell Viability Assay ◽  
Shenmai Injection ◽  
Oxidative Markers ◽  
Viability Assay

Abstract Background: Acute ischemic stroke (AIS) and following reperfusion therapy-induced cerebral ischemia reperfusion (I/R) injury have been recognized as an important subject of cerebrovascular disease with high mortality. Oxidative stress is an important pathological process of cerebral I/R injury. microRNA-19a (miR-19a) is involved in I/R. As the organ protectant agent, Shenmai Injection (SMI) is widely used in the clinical treatment of cerebral infarction. Purpose: This study aims to explore whether SMI can reduce oxidative stress by regulating miR-19a, thereby treating I/R injury. Methods: The oxidative stress state of PC12 cells was induced by H2O2, and then the cells were cultured with SMI. The therapeutic effect of SMI was evaluated by detecting cellular superoxide dismutase (SOD), malondialdehyde (MDA) and other oxidative markers with the kit. Western blot, PCR, immunofluorescence and other techniques were used to elucidate the potential mechanism of SMI. Results: Cell viability assay results showed that SMI could improve the viability of PC12 cells stimulated by H2O2. Compared with the H2O2 group, after SMI treatment, the contents of MDA and reactive oxygen species (ROS) were significantly reduced, while the activity of SOD was significantly increased, and SMI could reduce apoptosis by increasing the content of adenosine 5'-triphosphate (ATP) in cells and enhancing the mitochondrial membrane potential (∆Ψm). Western blot and qRT-PCR results showed that these effects were partially achieved through the AMPK/Sirt1/PGC-1α pathway. The level of miR-19a was significantly increased in H2O2 group, and SMI could protect the cells by reducing miR-19a. Further investigated the target of miR-19a, and transfected cells with miR-19a mimic and inhibitor respectively. We found that AdipoR2 was a direct target of miR-19a, and miR-19a could inhibit AdipoR2/PI3K/Akt/mTOR pathway. Conclusion:SMI can activate AMPK/Sirt1/PGC-1α and AdipoR2/PI3K/Akt/mTOR pathways by reducing miR-19a levels, and protect PC12 cells stimulated by H2O2.

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.

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.

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

Activation of Nrf2 by costunolide provides neuroprotective effect in PC12 cells

2019 ◽  
Vol 10 (7) ◽  
pp. 4143-4152 ◽  
Author(s):  
Shoujiao Peng ◽  
Yanan Hou ◽  
Juan Yao ◽  
Jianguo Fang
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Sesquiterpene Lactone ◽  
Pc12 Cells ◽  
Neuroprotective Effect ◽  
Neuroprotective Effects ◽  
Inula Helenium ◽  
Activating Transcription Factor

Costunolide (COS), a natural sesquiterpene lactone originally isolated from Inula helenium (Compositae), shows potent neuroprotective effects against oxidative stress-mediated injuries of PC12 cells via activating transcription factor Nrf2.

scholarly journals Neuroprotective Effects of Coreopsis lanceolata Flower Extract against Oxidative Stress-Induced Apoptosis in Neuronal Cells and Mice

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 951
Author(s):  
Hyung Don Kim ◽  
Ji Yeon Lee ◽  
Jeong-Yong Park ◽  
Dong Hwi Kim ◽  
Min Hye Kang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Pc12 Cells ◽  
Caspase 3 ◽  
Antioxidant Activities ◽  
Neuronal Cells ◽  
Water Extract ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Induced Apoptosis

(1) Background: Coreopsis lanceolata L. is a perennial plant of the family Asteraceae, and its flower is known to contain flavonoids with various bioactivities. We evaluated the effect of Coreopsis lanceolata L. flower (CLF) extracts on H2O2-induced oxidative stress (OS) in neuronal cells and mouse neurons. (2) Methods: The flowering part of CL was used as CLF1 (70% ethanol extract) and CLF2 (water extract), and 10 types of phenolic compounds were quantified using high-performance liquid chromatography. To evaluate the neuroprotective effects of CLF, the antioxidant activities of the extracts were measured, and the expression levels of antioxidant enzymes and proteins related to OS-induced apoptosis in neuronal cells and mouse neurons treated with the extracts were investigated. (3) Results: In the in vitro study, CLF ameliorated H2O2-induced oxidative stress and induced the expression of antioxidant enzymes in PC12 cells. Furthermore, CLF1 enhanced the expression of the Bcl-xL protein but reduced the expression of Bax and the cleavage of caspase-3. In the same manner, CLF1 showed neuroprotective effects against OS in vivo. Pretreatment with CLF1 (200 mg/kg) increased the Bcl-2 protein and decreased Bax compared with the 1-methyl-4-phenylpyridinium ion (MPP+)-treated C57BL/6 mice model group. Our results suggest that the protective effects of CLF1 on MPP+-induced apoptosis may be due to its anti-apoptotic activity, through regulating the expression of the Bcl-2 family. (4) Conclusions: CLF1 exerts neuroprotective effects against OS-induced apoptosis in PC12 cells in a Parkinson’s disease model mouse. This effect may be attributable to the upregulation of Bcl-2 protein expression, downregulation of Bax expression, and inhibition of caspase-3 activation. These data indicate that CLF may provide therapeutic value for the treatment of progressive neurodegenerative diseases.

scholarly journals Erratum: Rodriguez et al. Substance P Antagonism as a Novel Therapeutic Option to Enhance Efficacy of Cisplatin in Triple Negative Breast Cancer and Protect PC12 Cells against Cisplatin-Induced Oxidative Stress and Apoptosis. Cancers 2021, 13, 3871

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5178
Author(s):  
Emma Rodriguez ◽  
Guangsheng Pei ◽  
Zhongming Zhao ◽  
Sang T. Kim ◽  
Alexis German ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Substance P ◽  
Pc12 Cells ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Therapeutic Option ◽  
Original Version ◽  
Novel Therapeutic

One contributor’s name was missing in the original version of the authorship of the paper [...]

scholarly journals Silymarin versus Silibinin: Differential Antioxidant and Neuroprotective Effects against H2O2-induced Oxidative Stress in PC12 Cells

2016 ◽  
Vol 11 (5) ◽  
pp. 1934578X1601100 ◽  
Author(s):  
Hui-Hui Jiang ◽  
Fa-Shun Yan ◽  
Liang Shen ◽  
Hong-Fang Ji
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Pc12 Cells ◽  
Superoxide Anion ◽  
Active Component ◽  
Antioxidant Activities ◽  
Neuroprotective Effect ◽  
Neuroprotective Effects ◽  
Future Studies ◽  
Pheochromocytoma Pc12

The present study assessed comparatively the antioxidant activities of silymarin and its major active component silibinin and their neuroprotective effects against hydrogen peroxide (H2O2)-induced oxidative stress in rat pheochromocytoma PC12 cells. It was found that despite newly prepared silymarin and silibinin solution possessing comparable superoxide anion (O2.–)-scavenging activities, with time the activity of silymarin lowered slightly, but that of silibinin decreased dramatically. Both silymarin and silibinin suppressed H2O2-induced oxidative stress and apoptosis, and the neuroprotective effect of silymarin was overall relatively stronger than that of silibinin. The findings provided clues for future studies on therapeutic potentials of the whole silymarin or purified silibinin for neurodegenerative diseases.

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