Autophagy occurs within an hour of adenosine triphosphate treatment after nerve cell damage: the neuroprotective effects of adenosine triphosphate against apoptosis

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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Ethanol Extract of Maclura tricuspidata Fruit Protects SH-SY5Y Neuroblastoma Cells against H2O2-Induced Oxidative Damage via Inhibiting MAPK and NF-κB Signaling

International Journal of Molecular Sciences ◽

10.3390/ijms22136946 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6946

Author(s):

Weishun Tian ◽

Suyoung Heo ◽

Dae-Woon Kim ◽

In-Shik Kim ◽

Dongchoon Ahn ◽

...

Keyword(s):

Oxidative Stress ◽

Free Radical ◽

Oxidative Damage ◽

Cell Damage ◽

Antioxidant Properties ◽

Radical Scavenging ◽

Biologically Active ◽

Mitogen Activated Protein Kinase ◽

Protective Effects ◽

Neuroprotective Effects

Free radical generation and oxidative stress push forward an immense influence on the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Maclura tricuspidata fruit (MT) contains many biologically active substances, including compounds with antioxidant properties. The current study aimed to investigate the neuroprotective effects of MT fruit on hydrogen peroxide (H2O2)-induced neurotoxicity in SH-SY5Y cells. SH-SY5Y cells were pretreated with MT, and cell damage was induced by H2O2. First, the chemical composition and free radical scavenging properties of MT were analyzed. MT attenuated oxidative stress-induced damage in cells based on the assessment of cell viability. The H2O2-induced toxicity caused by ROS production and lactate dehydrogenase (LDH) release was ameliorated by MT pretreatment. MT also promoted an increase in the expression of genes encoding the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). MT pretreatment was associated with an increase in the expression of neuronal genes downregulated by H2O2. Mechanistically, MT dramatically suppressed H2O2-induced Bcl-2 downregulation, Bax upregulation, apoptotic factor caspase-3 activation, Mitogen-activated protein kinase (MAPK) (JNK, ERK, and p38), and Nuclear factor-κB (NF-κB) activation, thereby preventing H2O2-induced neurotoxicity. These results indicate that MT has protective effects against H2O2-induced oxidative damage in SH-SY5Y cells and can be used to prevent and protect against neurodegeneration.

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AC-YVAD-CMK Inhibits Pyroptosis and Improves Functional Outcome after Intracerebral Hemorrhage

BioMed Research International ◽

10.1155/2018/3706047 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 10

Author(s):

Xiao Lin ◽

Haotuo Ye ◽

Felix Siaw-Debrah ◽

Sishi Pan ◽

Zibin He ◽

...

Keyword(s):

Cell Death ◽

Intracerebral Hemorrhage ◽

Cell Damage ◽

Neuronal Cell ◽

Neurological Function ◽

Inflammatory Factors ◽

Neuroprotective Effects ◽

Caspase 1 ◽

Cell Death Pathways ◽

Cell Death Pathway

Intracerebral hemorrhage (ICH) refers to bleeding in the brain and is associated with the release of large amount of inflammasomes, and the activation of different cell death pathways. These cell death pathways lead to removal of inactivated and damaged cells and also result in neuronal cell damage. Pyroptosis is a newly discovered cell death pathway that has gained attention in recent years. This pathway mainly depends on activation of caspase-1-mediated cascades to cause cell death. We tested a well-known selective inhibitor of caspase-1, AC-YVAD-CMK, which has previously been found to have neuroprotective effects in ICH mice model, to ascertain its effects on the activation of inflammasomes mediated pyroptosis. Our results showed that AC-YVAD-CMK could reduce caspase-1 activation and inhibit IL-1β production and maturation, but has no effect on NLRP3 expression, an upstream inflammatory complex. AC-YVAD-CMK administration also resulted in reduction in M1-type microglia polarization around the hematoma, while increasing the number of M2-type cells. Furthermore, AC-YVAD-CMK treated mice showed some recovery of neurological function after hemorrhage especially at the hyperacute and subacute stage resulting in some degree of limb movement. In conclusion, we are of the view that AC-YVAD-CMK could inhibit pyroptosis, decrease the secretion or activation of inflammatory factors, and affect the polarization of microglia resulting in improvement of neurological function after ICH.

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Natural compounds attenuate heavy metal-induced PC12 cell damage

Journal of International Medical Research ◽

10.1177/0300060520930847 ◽

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.

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Rosmarinic acid mediated neuroprotective effects against H2O2-induced neuronal cell damage in N2A cells

Life Sciences ◽

10.1016/j.lfs.2014.07.010 ◽

2014 ◽

Vol 113 (1-2) ◽

pp. 7-13 ◽

Cited By ~ 51

Author(s):

Hadi Ghaffari ◽

M. Venkataramana ◽

Behrouz Jalali Ghassam ◽

S. Chandra Nayaka ◽

A. Nataraju ◽

...

Keyword(s):

Rosmarinic Acid ◽

Cell Damage ◽

Neuronal Cell ◽

Neuroprotective Effects ◽

N2a Cells

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Neuroprotective Effects of Mitochondria-Targeted Plastoquinone in a Rat Model of Neonatal Hypoxic–Ischemic Brain Injury

Molecules ◽

10.3390/molecules23081871 ◽

2018 ◽

Vol 23 (8) ◽

pp. 1871 ◽

Cited By ~ 14

Author(s):

Denis Silachev ◽

Egor Plotnikov ◽

Irina Pevzner ◽

Ljubava Zorova ◽

Anastasia Balakireva ◽

...

Keyword(s):

Oxidative Stress ◽

Targeted Delivery ◽

Cell Damage ◽

Brain Cell ◽

Neuroprotective Effects ◽

Neonatal Hypoxia ◽

Hypoxia Ischemia ◽

Causes Of Mortality ◽

High Production ◽

The Brain

Neonatal hypoxia–ischemia is one of the main causes of mortality and disability of newborns. To study the mechanisms of neonatal brain cell damage, we used a model of neonatal hypoxia–ischemia in seven-day-old rats, by annealing of the common carotid artery with subsequent hypoxia of 8% oxygen. We demonstrate that neonatal hypoxia–ischemia causes mitochondrial dysfunction associated with high production of reactive oxygen species, which leads to oxidative stress. Targeted delivery of antioxidants to the mitochondria can be an effective therapeutic approach to treat the deleterious effects of brain hypoxia–ischemia. We explored the neuroprotective properties of the mitochondria-targeted antioxidant SkQR1, which is the conjugate of a plant plastoquinone and a penetrating cation, rhodamine 19. Being introduced before or immediately after hypoxia–ischemia, SkQR1 affords neuroprotection as judged by the diminished brain damage and recovery of long-term neurological functions. Using vital sections of the brain, SkQR1 has been shown to reduce the development of oxidative stress. Thus, the mitochondrial-targeted antioxidant derived from plant plastoquinone can effectively protect the brain of newborns both in pre-ischemic and post-stroke conditions, making it a promising candidate for further clinical studies.

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Molecular Targets Involved in the Neuroprotection Mediated by Terpenoids

Planta Medica ◽

10.1055/a-0953-6738 ◽

2019 ◽

Vol 85 (17) ◽

pp. 1304-1315 ◽

Cited By ~ 4

Author(s):

Laura González-Cofrade ◽

Beatriz de las Heras ◽

Luis Apaza Ticona ◽

Olga M. Palomino

Keyword(s):

Therapeutic Potential ◽

Cell Damage ◽

Biological Activities ◽

Neuronal Cell ◽

Molecular Targets ◽

Research Activity ◽

Neuroprotective Effects ◽

Therapeutic Value ◽

Wide Range ◽

Drug Leads

AbstractNatural products and their derivatives represent the most consistently successful source of drug leads. Terpenoids, a structurally diverse group, are secondary metabolites widely distributed in nature, endowed with a wide range of biological activities such as antibacterial, anti-inflammatory, antitumoral, or neuroprotective effects, which consolidate their therapeutic value. During the last decades, and taking into consideration the prevalence of aging-related diseases, research activity into the neuroprotective effects of these types of compounds has increased enormously. Several signaling pathways involved in neuroprotection are targets of their mechanism of action and mediate their pleiotropic protective activity in neuronal cell damage. In the present review, molecular basis of the neuroprotection exerted by terpenoids is presented, focusing on preclinical evidence of the therapeutic potential of diterpenoids and triterpenoids on neurodegenerative disorders. By acting on diverse mechanisms simultaneously, terpenoids have been emphasized as promising multitarget agents.

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NEUROPROTECTIVE EFFECTS OF GUARANA (PAULLINIA CUPANA MART.) AGAINST VINCRISTINE IN VITRO EXPOSURE

Journal of Prevention of Alzheimer's Disease ◽

10.14283/jpad.2017.45 ◽

2017 ◽

pp. 1-6

Author(s):

C.F. Veloso ◽

A.K. Machado ◽

F.C. Cadoná ◽

V.F. Azzolin ◽

I.B.M. Cruz ◽

...

Keyword(s):

Cell Viability ◽

Monolayer Culture ◽

Cell Damage ◽

Neuroprotective Effect ◽

In Vitro Study ◽

Oxygen Species ◽

Neuroprotective Effects ◽

Hydroalcoholic Extract ◽

Mice Brain

Background: Vincristine (VCR) is not a specific chemotherapeutic drug, responsible for cause several side effects. In this sense, many natural products have been studied to reduce this problem. Objetives: To examine the guarana neuroprotective effect in mice brain and cerebellum cells against vincristine (VCR) exposition. Design: An in vitro study was performed using mice brain and cerebellum mice in monolayer culture. First, cells were exposed to VCR (0.009 µM for 24 hours and 0.0007 µM for 72 hours) to measure the cytotoxicity effect. Also, the cellular effect of hydroalcoholic extract of guarana (10; 30; 100 and 300 μg/mL) was evaluated in the same cells in 24 and 72 hours. After that, cells were exposed to VCR and guarana extract to evaluate the neuroprotective effect of guarana. Measurements: Cell viability was analyzed by MTT, Free dsDNA and LHD Assays. Moreover, metabolism oxidative profile was evaluated by reactive oxygen species (ROS), lipoperoxidation (LPO) and catalase (CAT) levels through DCFH-DA, TBARS and Catalase Activity Assays, respectively. Results: Our findings revealed that VCR caused neuronal cytotoxicity by reducing cell viability and increasing ROS and LPO levels. On the other hand, guarana did not cause cell damage in none of tested concentrations. In addition, guarana exhibited a notable protective effect on brain and cerebellum cells exposed to VCR by increasing cell viability, stimulating CAT activity, reducing levels of ROS and LPO. Conclusions: In this sense, guaraná is a remarkable antioxidant fruit that could be a target in new therapies development to reduce VCR neurotoxicity.

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