Ribozyme-mediated inhibition of caspase-3 activity reduces apoptosis induced by 6-hydroxydopamine in PC12 cells

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.

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Luteolin Modulates 6-Hydroxydopamine-Induced Transcriptional Changes of Stress Response Pathways in PC12 Cells

PLoS ONE ◽

10.1371/journal.pone.0097880 ◽

2014 ◽

Vol 9 (5) ◽

pp. e97880 ◽

Cited By ~ 26

Author(s):

Ling-Wei Hu ◽

Jui-Hung Yen ◽

Yi-Ting Shen ◽

Kuan-Yi Wu ◽

Ming-Jiuan Wu

Keyword(s):

Stress Response ◽

Pc12 Cells ◽

Transcriptional Changes ◽

6 Hydroxydopamine

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Curcumin I Mediates Neuroprotective Effect Through Attenuation of Quinoprotein Formation, p-p38 MAPK Expression, and Caspase-3 Activation in 6-Hydroxydopamine Treated SH-SY5Y Cells

Phytotherapy Research ◽

10.1002/ptr.5036 ◽

2013 ◽

Vol 28 (4) ◽

pp. 611-616 ◽

Cited By ~ 17

Author(s):

Benjawan Meesarapee ◽

Anusorn Thampithak ◽

Yamaratee Jaisin ◽

Pimtip Sanvarinda ◽

Apichart Suksamrarn ◽

...

Keyword(s):

P38 Mapk ◽

Caspase 3 ◽

Neuroprotective Effect ◽

6 Hydroxydopamine ◽

Curcumin I

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Protective Effects of Crataegus pinnatifida Extracts and Crataegolic Acid Against Neurotoxicity of Paraquat in PC12 Cells

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.20:76-83 ◽

2021 ◽

Vol 20 (1) ◽

pp. 76-83

Author(s):

Chi-Sen Chang ◽

Yuh-Chiang Shen ◽

Chi-Wen Juan ◽

Chia-Lin Chang ◽

Po-Kai Lin

Keyword(s):

Reactive Oxygen Species ◽

Pc12 Cells ◽

Cell Apoptosis ◽

Active Component ◽

Caspase 3 ◽

Reactive Oxygen ◽

B Cell Lymphoma ◽

Oxygen Species ◽

Protein Levels ◽

Crataegus Pinnatifida

The neuroprotective mechanisms of Crataegus pinnatifida extracts and crataegolic acid were studied using paraquat induced cytotoxicity in PC12 cells. C. pinnatifida extracts were prepared using hexane, ethyl acetate, and 95% ethanol. Additionally, crataegolic acid (also known as maslinic acid) was found in C. pinnatifida extracts. Assessment methods included the examinations of cytotoxicity, intracellular reactive oxygen species and calcium changes, activity of caspase-3 and α-synuclein, apoptotic cell death, and the expression levels of the B-cell lymphoma 2 (Bcl-2) and BCL2-associated X (Bax) proteins to investigate the neuroprotective mechanisms of C. pinnatifida extracts and its active component, crataegolic acid. The three extracts and crataegolic acid exhibited potent neuroprotective actions against paraquat induced PC12 cell apoptosis at 5–20µg/mL and 80–100µM concentrations, respectively. The key protective mechanisms included decreasing cell apoptosis, upregulating Bcl-2 protein levels, and downregulating Bax protein levels. The 95% ethanol extract also decreased paraquat induced reactive oxygen species production, calcium overloading, and caspase-3 and α-synuclein activities. The beneficial effects of these extracts could be explained by the active component, crataegolic acid that also inhibited paraquat-induced apoptosis through the suppression of reactive oxygen species generation and the caspase-3 signaling pathway.

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Phytic Acid Protects against 6-Hydroxydopamine-Induced Dopaminergic Neuron Apoptosis in Normal and Iron Excess Conditions in a Cell Culture Model

Parkinson s Disease ◽

10.4061/2011/431068 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6 ◽

Cited By ~ 8

Author(s):

Qi Xu ◽

Anumantha G. Kanthasamy ◽

Manju B. Reddy

Keyword(s):

Dna Fragmentation ◽

Phytic Acid ◽

Caspase 3 ◽

Fold Increase ◽

Iron Chelator ◽

Culture Model ◽

A Cell ◽

Induced Apoptosis ◽

6 Hydroxydopamine ◽

Stress Dependent

Iron may play an important role in Parkinson's disease (PD) since it can induce oxidative stress-dependent neurodegeneration. The objective of this study was to determine whether the iron chelator, phytic acid (IP6) can protect against 6-hydroxydopamine- (6-OHDA-) induced apoptosis in immortalized rat mesencephalic dopaminergic cells under normal and iron-excess conditions. Caspase-3 activity was increased about 6-fold after 6-OHDA treatment (compared to control; ) and 30 μmol/L IP6 pretreatment decreased it by 38% (). Similarly, a 63% protection () against 6-OHDA induced DNA fragmentation was observed with IP6 pretreatment. Under iron-excess condition, a 6-fold increase in caspase-3 activity () and a 42% increase in DNA fragmentation () with 6-OHDA treatment were decreased by 41% () and 27% (), respectively, with 30 μmol/L IP6. Together, our data suggest that IP6 protects against 6-OHDA-induced cell apoptosis in both normal and iron-excess conditions, and IP6 may offer neuroprotection in PD.

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