Butanol Extract of Tinospora cordifolia Ameliorates Cognitive Deficits Associated with Glutamate-Induced Excitotoxicity: A Mechanistic Study Using Hippocampal Neurons

Sharma, Anuradha; Kalotra, Shikha; Bajaj, Payal; Singh, Harpal; Kaur, Gurcharan

doi:10.1007/s12017-019-08566-2

Cited by 23 publications

(7 citation statements)

References 73 publications

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“…It was found that the tested extract exerted protective effects against glutamate-induced toxicity by maintaining MAP-2 expression in the cells to near control levels and improves cognitive impairments resulted from glutamate‐induced neurotoxicity in Wistar strain albino rats models by targeting downstream NMDAR, ERK, PI3K/Akt pathways of synaptic plasticity. Tinosporicide (45) was isolated from the extract, which was potent under in-vitro condition, at a low dose (25 ng/mL) as compared to crude extract (20 μg/mL) [ 167 ].…”

Section: Medicinal Plants and Their Isolated Phytochemicals In Managi...mentioning

confidence: 99%

Potential of Medicinal Plants as Neuroprotective and Therapeutic Properties Against Amyloid-β-Related Toxicity, and Glutamate-Induced Excitotoxicity in Human Neural Cells

Lobine

Sadeer

Jugreet

et al. 2021

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: Alzheimer’s disease (AD) and Parkinson disease (PD) are notorious neurodegenerative diseases amongst the general population. Being age-associated diseases, the prevalence of AD and PD is forecasted to rapidly escalate with the progressive aging population of the world. These diseases are complex and multifactorial. Among the different events, amyloid β peptide (Aβ) induced toxicity is a well‐established pathway of neuronal cell death which plays a vital function in AD. Glutamate, the major excitatory transmitter, acts a neurotoxin when present in excess at the synapses; this latter mechanism is termed as excitotoxicity. It is hypothesised that glutamate-induced excitotoxicity contributes to the pathogenesis of AD and PD. No cure for AD and PD is currently available and the currently approved drugs available to treat these diseases have limited effectiveness and pose adverse effects. Indeed, plants have been a major source for the discovery of novel pharmacologically active compounds for distinct pathological conditions. Diverse plant species employed for brain related disorders in the traditional medicine are being explored to determine them scientific rationale behind their uses. Herein, we present a comprehensive review of plants and their constituents have shown promise in reversing the (i) amyloid-β -related toxicity in AD models and (ii) glutamate-induced excitotoxicity in AD and PD models. This review summarizes information with regard to the phytochemistry, biological and cellular activities as well as clinical trials of several plant species in view to provide adequate scientific baseline information that could be used in drug development process, thereby providing effective leads for AD and PD.

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Section: Medicinal Plants and Their Isolated Phytochemicals In Managi...mentioning

confidence: 99%

Potential of Medicinal Plants as Neuroprotective and Therapeutic Properties Against Amyloid-β-Related Toxicity, and Glutamate-Induced Excitotoxicity in Human Neural Cells

Lobine

Sadeer

Jugreet

et al. 2021

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“…In our previous study, we demonstrated that Tc has neuroprotective as well as anti-neuroin ammatory activity in mice brain mainly due to inhibition of NF-kB and other proin ammatory molecule such as TNF-α, IL-12, IL-1β, and restoration of Tyrosine hydroxylase levels, a key enzyme in the synthesis of DA [19]. reported that butanolic extract of Tc has reversed the glutamate-induced neurodegeneration in hippocampus region of rat brain [20].…”

Section: Introductionmentioning

confidence: 95%

Unraveling the neuroprotective effect of Tinospora cordifolia in Parkinsonian mouse model through proteomics Approach.

Birla

Keswani

Singh

et al. 2021

Preprint

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Stress-induced dopaminergic (DAergic) neuronal death in the midbrain region is the primary cause of Parkinson’s disease (PD). From the discovery of L-dopa, multiple drugs were discovered to improve lifestyle of PD patients, but they failed due to their multiple side effects. Tinospora cordifolia (Tc), a medicinal herb has been used in traditional medicines to treat neurodegenerative diseases. In our previous study, the neuroprotective role of Tc against MPTP intoxicated Parkinsonian mice was reported. Here, we further explore the neuroprotective molecular mechanisms of Tc in Rotenone (ROT) intoxicated mouse model through proteomics approach. Mice were pretreated with Tc extract by oral administration, followed by ROT-intoxication. Behavioral tests were performed to check motor functions of mice. Protein was isolated, and label free quantification (LFQ) was carried out to identify differentially expressed protein (DEPs) in control vs. PD and PD vs. treatment group. In this study, we report 800 DEPs in control vs. PD and 133 in PD vs. Treatment group. In silico tools clearly demonstrate significant enrichment of biochemical and molecular pathways with DEPs which are known to be important for PD progression including mitochondrial gene expression, PD pathways, TGF-β signaling, Alzheimer’s disease etc. This results were further validated by qRT-PCR and found that the expression of target gene were identical to the proteomics data. This study provides a novel insight for the disease progression as well new therapeutic tagets. More importantly, it demonstrates that Tc exerts the therapeutic effects through the regulation of multiple pathways to protect DAergic neurons.

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“…19 Additionally, Sharma et al reported that the butanolic extract of Tc reversed glutamate-induced neurodegeneration in the hippocampal region of the rat brain. 20 By employing proteomics, we can identify novel molecular pathways involved in the progression of PD. Identifying these pathways can serve to aid in early disease diagnosis and prognosis and to monitor the stage of disease development as well as recognition of advanced drug targets.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Tc also exhibits anti-inflammatory activity in PD mice, owing to its ability to inhibit NF-κB and associated proinflammatory cytokines including TNF-α, IL-12, and IL-1β . Additionally, Sharma et al reported that the butanolic extract of Tc reversed glutamate-induced neurodegeneration in the hippocampal region of the rat brain …”

Section: Introductionmentioning

confidence: 99%

Unraveling the Neuroprotective Effect of Tinospora cordifolia in a Parkinsonian Mouse Model through the Proteomics Approach

Birla

Keswani

Singh

et al. 2021

ACS Chem. Neurosci.

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Stress-induced dopaminergic (DAergic) neuronal death in the midbrain region is the primary cause of Parkinson’s disease (PD). Following the discovery of l-dopa, multiple drugs have been developed to improve the lifestyle of PD patients; however, none have been suitable for clinical use due to their multiple side effects. Tinospora cordifolia has been used in traditional medicines to treat neurodegenerative diseases. Previously, we reported the neuroprotective role of Tc via inhibition of NF-κB-associated proinflammatory cytokines against MPTP-intoxicated Parkinsonian mice. In the present study, we investigated the neuroprotective molecular mechanism of Tc in a rotenone (ROT)-intoxicated mouse model, using a proteomics approach. Mice were pretreated with Tc extract by oral administration, followed by ROT intoxication. Behavioral tests were performed to check motor functions of mice. Protein was isolated, and label-free quantification (LFQ) was carried out to identify differentially expressed protein (DEP) in control vs PD and PD vs treatment groups. Results were validated by qRT-PCR with the expression of target genes correlating with the proteomics data. In this study, we report 800 DEPs in control vs PD and 133 in PD vs treatment groups. In silico tools demonstrate significant enrichment of biochemical and molecular pathways with DEPs, which are known to be important for PD progression including mitochondrial gene expression, PD pathways, TGF-β signaling, and Alzheimer’s disease. This study provides novel insights into the PD progression as well as new therapeutic targets. More importantly, it demonstrates that Tc can exert therapeutic effects by regulating multiple pathways, resulting in neuroprotection.

show abstract

Butanol Extract of Tinospora cordifolia Ameliorates Cognitive Deficits Associated with Glutamate-Induced Excitotoxicity: A Mechanistic Study Using Hippocampal Neurons

Cited by 23 publications

References 73 publications

Potential of Medicinal Plants as Neuroprotective and Therapeutic Properties Against Amyloid-β-Related Toxicity, and Glutamate-Induced Excitotoxicity in Human Neural Cells

Potential of Medicinal Plants as Neuroprotective and Therapeutic Properties Against Amyloid-β-Related Toxicity, and Glutamate-Induced Excitotoxicity in Human Neural Cells

Unraveling the neuroprotective effect of Tinospora cordifolia in Parkinsonian mouse model through proteomics Approach.

Unraveling the Neuroprotective Effect of Tinospora cordifolia in a Parkinsonian Mouse Model through the Proteomics Approach

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