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

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.

Download Full-text

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.

Download Full-text

Sodium Butyrate Protects N2a Cells against Aβ Toxicity In Vitro

Mediators of Inflammation ◽

10.1155/2020/7605160 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Jingxuan Sun ◽

Boyu Yuan ◽

Yancheng Wu ◽

Yuhong Gong ◽

Wenjin Guo ◽

...

Keyword(s):

Sodium Butyrate ◽

Cell Injury ◽

Cell Damage ◽

Protective Effects ◽

Neuroprotective Effects ◽

Fatty Acid Salt ◽

Cognitive Improvement ◽

N2a Cells ◽

Underlying Mechanisms

Alzheimer’s disease (AD) is a common neurodegenerative disease. Aβ plays an important role in the pathogenesis of AD. Sodium butyrate (NaB) is a short-chain fatty acid salt that exerts neuroprotective effects such as anti-inflammatory, antioxidant, antiapoptotic, and cognitive improvement in central nervous system diseases. The aim of this study is to research the protective effects of NaB on neurons against Aβ toxicity and to uncover the underlying mechanisms. The results showed that 2 mM NaB had a significant improvement effect on Aβ-induced N2a cell injury, by increasing cell viability and reducing ROS to reduce injury. In addition, by acting on the GPR109A receptor, NaB regulates the expression of AD-related genes such as APP, NEP, and BDNF. Therefore, NaB protects N2a cells from Aβ-induced cell damage through activating GPR109A, which provides an innovative idea for the treatment of AD.

Download Full-text

Contribution of ginsenosides Rg1, Rb1 to the neuroprotective effect of Panax notoginseng in mouse organotypic hippocampal slice cultures exposed to oxygen and glucose deprivation

Vietnam Journal of Science Technology and Engineering ◽

10.31276/vjste.63(2).64-69 ◽

2021 ◽

Vol 63 (2) ◽

pp. 64-69

Author(s):

Nguyen Thi Thanh Loan ◽

◽

Le Thi Xoan ◽

Pham Thi Nguyet Hang ◽

Nguyen Van Tai ◽

...

Keyword(s):

Hippocampal Slice ◽

Cell Damage ◽

Neuroprotective Effect ◽

Neuronal Cell ◽

Glucose Deprivation ◽

Panax Notoginseng ◽

Ginsenoside Rg1 ◽

Neuroprotective Effects ◽

Oxygen And Glucose Deprivation ◽

Mk 801

We previously demonstrated that Panax notoginseng (pNG) root extract treatments exertedneuroprotective effects on brain injuries using middle cerebral artery occlusion in mice. The present study aims to investigate the neuroprotective effects of PNG extract and its ginsenosides Rg1 and Rb1 on ischemic neuronal damage caused by oxygen and glucose deprivation (OGD) in mouse organotypic hippocampal slice cultures (OHSCs). Before the experiments, hippocampal slices collected from 7-day-old Swiss mice were cultured for 7 days. OGD was triggered in OHSCs for 30, 60, or 90 min with the aim of finding the optimal period of OGD for drug testing. PNG extract (10, 30 μg/ml), ginsenosides Rg1 and Rb1 (5, 25 μM), or MK-801 25 μM, a reference drug, was added to the culture medium 24 h before OGD and these treatments were continued for 24 h after the optimum 60-min period of OGD. After 24 h of OGD exposure, the measurement of propidium iodide uptake was analysed in OHSCs to evaluate neuronal cell damage. The results showed that OGD time-dependently increased PI uptake of the OHSCs. PNG 30 μg/ml treatment reduced the OGD-induced neuronal cell damage in OHSCs. Ginsenosides Rg1 25 μM, Rb1 (5, 25 μM), as well as MK-801 (25 μM) significantly inhibited PI uptake 24 h after OGD exposure. However, ginsenoside Rg1 5 μM did not show any significant effects on the OGD-induced neuronal cell damage. These findings indicated that ginsenosides Rg1 and Rb1 contributed to the neuroprotective effects of PNG against ischemic damage in OHSCs and the neuroprotective effect of ginsenoside Rb1 was stronger than that of ginsenoside Rg1.

Download Full-text

Protective Effects of p-Coumaric Acid Isolated from Vaccinium bracteatum Thunb. Leaf Extract on Corticosterone-Induced Neurotoxicity in SH-SY5Y Cells and Primary Rat Cortical Neurons

Processes ◽

10.3390/pr9050869 ◽

2021 ◽

Vol 9 (5) ◽

pp. 869

Author(s):

Dool-Ri Oh ◽

Moon-Jong Kim ◽

Eun-Jin Choi ◽

Yujin Kim ◽

Hak-Sung Lee ◽

...

Keyword(s):

Cortical Neurons ◽

Cell Damage ◽

Primary Cultures ◽

Water Extract ◽

Neuronal Cell ◽

Protective Effects ◽

Coumaric Acid ◽

Cortical Cells ◽

Neuroprotective Effects ◽

Creb Phosphorylation

Corticosterone (CORT)-induced oxidative stress and neurotoxicity can cause neuronal dysfunction and mental disorders. In the present study, we investigated the effects and mechanism of the HP-20 resin fraction of the water extract of Vaccinium bracteatum leaves (NET-D1602) and its bioactive compound p-coumaric acid on neuronal cell damage in SH-SY5Y cells and primary culture of rat cortical cells. NET-D1602 and p-coumaric acid significantly improved cell viability in CORT-induced neurotoxicity in SH-SY5Y cells and primary cultures of rat cortical cells, and increased the activities of antioxidant enzymes (superoxide dismutase and catalase) against CORT-induced neurotoxicity in SH-SY5Y cells. NET-D1602 and p-coumaric acid increased the phosphorylation levels of ERK1/2 and cAMP response element-binding protein (CREB) in cortical neurons. In addition, CREB phosphorylation by NET-D1602 and p-coumaric acid was dramatically reversed by PKA, c-Raf/ERK, PI3K, and mTOR inhibitors. Lastly, we demonstrated the neuroprotective effects of NET-D1602 (3 and 10 μg/mL) and p-coumaric acid (3 and 10 μM) via increased CREB phosphorylation in CORT-induced neurotoxicity mediated via the ERK1/2, Akt, and mTOR pathways. These results suggest that p-coumaric acid is a potential neuroprotective component of NET-D1602, with the ability to protect against CORT-induced neurotoxicity by regulating ERK1/2, Akt, and mTOR-mediated CREB phosphorylation.

Download Full-text

Neuroprotection Comparison of Rosmarinic Acid and Carnosic Acid in Primary Cultures of Cerebellar Granule Neurons

Molecules ◽

10.3390/molecules23112956 ◽

2018 ◽

Vol 23 (11) ◽

pp. 2956 ◽

Cited By ~ 7

Author(s):

Faten Taram ◽

Elizabeth Ignowski ◽

Nathan Duval ◽

Daniel Linseman

Keyword(s):

Rosmarinic Acid ◽

Nitrosative Stress ◽

Primary Cultures ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Carnosic Acid ◽

Cerebellar Granule Neurons ◽

Granule Neurons ◽

Neuroprotective Effects ◽

Cerebellar Granule

Neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, and Parkinson’s disease, are characterized by the progressive loss of neurons in specific regions of the brain and/or spinal cord. Neuronal cell loss typically occurs by either apoptotic or necrotic mechanisms. Oxidative stress and nitrosative stress, along with excitotoxicity and caspase activation, have all been implicated as major underlying causes of neuronal cell death. Diverse nutraceuticals (bioactive compounds found in common foods) have been shown to have neuroprotective effects in a variety of in vitro and in vivo disease models. In the current study, we compared the neuroprotective effects of two polyphenolic compounds, rosmarinic acid and carnosic acid, which are both found at substantial concentrations in the herb rosemary. The capacity of these compounds to rescue primary cultures of rat cerebellar granule neurons (CGNs) from a variety of stressors was investigated. Both polyphenols significantly reduced CGN death induced by the nitric oxide donor, sodium nitroprusside (nitrosative stress). Rosmarinic acid uniquely protected CGNs from glutamate-induced excitotoxicity, while only carnosic acid rescued CGNs from caspase-dependent apoptosis induced by removal of depolarizing extracellular potassium (5K apoptotic condition). Finally, we found that carnosic acid protects CGNs from 5K-induced apoptosis by activating a phosphatidylinositol 3-kinase (PI3K) pro-survival pathway. The shared and unique neuroprotective effects of these two compounds against diverse modes of neuronal cell death suggest that future preclinical studies should explore the potential complementary effects of these rosemary polyphenols on neurodegenerative disease progression.

Download Full-text

Neuroprotective Effects of Hydroalcoholic Extract of Ocimum sanctum Against H2O2 Induced Neuronal Cell Damage in SH-SY5Y Cells via Its Antioxidative Defence Mechanism

Neurochemical Research ◽

10.1007/s11064-013-1128-7 ◽

2013 ◽

Vol 38 (10) ◽

pp. 2190-2200 ◽

Cited By ~ 33

Author(s):

M. P. Venuprasad ◽

Kandikattu Hemanth Kumar ◽

Farhath Khanum

Keyword(s):

Cell Damage ◽

Neuronal Cell ◽

Ocimum Sanctum ◽

Defence Mechanism ◽

Neuroprotective Effects ◽

Hydroalcoholic Extract ◽

Antioxidative Defence

Download Full-text

Chrysin Protects against Memory and Hippocampal Neurogenesis Depletion in D-Galactose-Induced Aging in Rats

Nutrients ◽

10.3390/nu12041100 ◽

2020 ◽

Vol 12 (4) ◽

pp. 1100

Author(s):

Ram Prajit ◽

Nataya Sritawan ◽

Kornrawee Suwannakot ◽

Salinee Naewla ◽

Anusara Aranarochana ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Survival ◽

Brain Aging ◽

Cell Damage ◽

Neuronal Cell ◽

Hippocampal Neurogenesis ◽

Neuroprotective Effects ◽

Ki 67 ◽

Novel Object ◽

Immature Neurons

The interruption of hippocampal neurogenesis due to aging impairs memory. The accumulation of D-galactose (D-gal), a monosaccharide, induces brain aging by causing oxidative stress and inflammation, resulting in neuronal cell damage and memory loss. Chrysin, an extracted flavonoid, has neuroprotective effects on memory. The present study aimed to investigate the effect of chrysin on memory and hippocampal neurogenesis in brains aged using D-gal. Male Sprague-Dawley rats received either D-gal (50 mg/kg) by i.p. injection, chrysin (10 or 30 mg/kg) by oral gavage, or D-gal (50 mg/kg) and chrysin (10 or 30 mg/kg) for 8 weeks. Memory was evaluated using novel object location (NOL) and novel object recognition (NOR) tests. Hippocampal neurogenesis was evaluated using Ki-67, 5-bromo-2′-deoxyuridine (BrdU), and doublecortin (DCX) immunofluorescence staining to determine cell proliferation, cell survival, and number of immature neurons, respectively. We found that D-gal administration resulted in memory impairment as measured by NOL and NOR tests and in depletions in cell proliferation, cell survival, and immature neurons. However, co-treatment with chrysin (10 or 30 mg/kg) attenuated these impairments. These results suggest that chrysin could potentially minimize memory and hippocampal neurogenesis depletions brought on by aging.

Download Full-text