Alpha-asarone improves cognitive function of aged rats by alleviating neuronal excitotoxicity via GABAA receptors

Chen, Yu; Gao, Xin; Liu, Qi; Zeng, Lili; Zhang, Kun; Mu, Keman; Zhang, Di; Zou, Huixi; Wu, Nan; Ou, Jierui; Wang, Qiantao; Mao, Shengjun

doi:10.1016/j.neuropharm.2019.107843

Cited by 25 publications

(27 citation statements)

References 49 publications

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“…Moreover, the protective effects of NMZM against scopolamine-induced depression of LTP was partly dependent on the potentiation of GABA A receptors (Jiang et al, 2018). Alpha-asarone (ASA) is an essential oil isolated from the traditional Chinese medicinal herb Acorus gramineus that has been used to treat respiratory diseases and neural disorders for centuries in traditional Chinese and Indian herbal medicine (Huang et al, 2013;Rajput et al, 2014;Chen et al, 2020). ASA has positive neuroprotective effects and improves cognition in rodent models (Gu et al, 2010;Kumar et al, 2012;Mao et al, 2015).…”

Section: Targeting Gaba Neurotransmittersmentioning

confidence: 99%

“…ASA has positive neuroprotective effects and improves cognition in rodent models (Gu et al, 2010;Kumar et al, 2012;Mao et al, 2015). Chen et al found that ASA had an anti-AD effect in aged rats with cognitive deficits by inhibiting neuronal injury and decreasing Aβ 1−42 levels in the hippocampus, ultimately rescuing the cognitive deficits (Chen et al, 2020). ASA also had neuroprotective effects on primary hippocampal neurons impaired by glutamate.…”

Section: Targeting Gaba Neurotransmittersmentioning

confidence: 99%

“…ASA also had neuroprotective effects on primary hippocampal neurons impaired by glutamate. Further computer modeling and whole-cell patch-clamp recording studies suggested that ASA, as a GABA A R-positive allosteric modulator, can bind to GABA A R and improve cognitive function by reducing neuronal overexcitation ( Chen et al, 2020 ). Therefore, these studies suggest that treatment with GABA A receptor agonists or positive allosteric regulators could be a potential strategy for improving cognitive function in the elderly and in AD patients.…”

Section: Targeting Gaba Neurotransmittersmentioning

confidence: 99%

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GABAergic Inhibitory Interneuron Deficits in Alzheimer’s Disease: Implications for Treatment

et al. 2020

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Alzheimer's disease (AD) is a neurodegenerative disorder characterized clinically by severe cognitive deficits and pathologically by amyloid plaques, neuronal loss, and neurofibrillary tangles. Abnormal amyloid β-protein (Aβ) deposition in the brain is often thought of as a major initiating factor in AD neuropathology. However, gammaaminobutyric acid (GABA) inhibitory interneurons are resistant to Aβ deposition, and Aβ decreases synaptic glutamatergic transmission to decrease neural network activity. Furthermore, there is now evidence suggesting that neural network activity is aberrantly increased in AD patients and animal models due to functional deficits in and decreased activity of GABA inhibitory interneurons, contributing to cognitive deficits. Here we describe the roles played by excitatory neurons and GABA inhibitory interneurons in Aβ-induced cognitive deficits and how altered GABA interneurons regulate AD neuropathology. We also comprehensively review recent studies on how GABA interneurons and GABA receptors can be exploited for therapeutic benefit. GABA interneurons are an emerging therapeutic target in AD, with further clinical trials urgently warranted.

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Section: Targeting Gaba Neurotransmittersmentioning

confidence: 99%

Section: Targeting Gaba Neurotransmittersmentioning

confidence: 99%

Section: Targeting Gaba Neurotransmittersmentioning

confidence: 99%

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GABAergic Inhibitory Interneuron Deficits in Alzheimer’s Disease: Implications for Treatment

et al. 2020

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“…Numerous in vivo studies have confirmed the positive effects of application of asarone derivatives, such as αor β-asarone, on cognitive function and alleviation of AD symptoms in animal models [296][297][298]. Anti-amyloidogenic properties of mentioned compounds have also been observed in the PC12 cell line, and likewise an anti-neuroinflammatory effect in BV2 microglial cells [299].…”

Section: β-Asaronementioning

confidence: 82%

The PERK-Dependent Molecular Mechanisms as a Novel Therapeutic Target for Neurodegenerative Diseases

Rozpędek‐Kamińska

Siwecka

Wawrzynkiewicz

et al. 2020

IJMS

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Higher prevalence of neurodegenerative diseases is strictly connected with progressive aging of the world population. Interestingly, a broad range of age-related, neurodegenerative diseases is characterized by a common pathological mechanism—accumulation of misfolded and unfolded proteins within the cells. Under certain circumstances, such protein aggregates may evoke endoplasmic reticulum (ER) stress conditions and subsequent activation of the unfolded protein response (UPR) signaling pathways via the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-dependent manner. Under mild to moderate ER stress, UPR has a pro-adaptive role. However, severe or long-termed ER stress conditions directly evoke shift of the UPR toward its pro-apoptotic branch, which is considered to be a possible cause of neurodegeneration. To this day, there is no effective cure for Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), or prion disease. Currently available treatment approaches for these diseases are only symptomatic and cannot affect the disease progression. Treatment strategies, currently under detailed research, include inhibition of the PERK-dependent UPR signaling branches. The newest data have reported that the use of small-molecule inhibitors of the PERK-mediated signaling branches may contribute to the development of a novel, ground-breaking therapeutic approach for neurodegeneration. In this review, we critically describe all the aspects associated with such targeted therapy against neurodegenerative proteopathies.

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“…The levels of γ-aminobutyric acid in the brain of patients with opioid addiction were significantly reduced, which was positively related to cognitive impairment [49]. Alpha-asarone, the major ingredient isolated from the Chinese medicinal herb Acorus tatarinowii Schott, can improve the cognitive function of AD rats by enhancing the γ-aminobutyric acid system, inhibiting the overexcitation of hippocampal neurons, and reducing the deposition of amyloid β-protein (Aβ) [50]. Therefore, γ-aminobutyric acid is involved in the development of cognitive impairment, and its specific mechanism in DCI needs further study.…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology Dissection of Multi-scale Mechanisms of Action of Tu-Xian Mixture for the Treatment of Diabetic Cognitive Impairment

Yan

Sun

et al. 2020

Preprint

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Background Traditional Chinese medicine (TCM) has long been used in the treatment of diabetic cognitive impairment (DCI), and Tu-Xian mixture is one of the prescriptions. This study used a network pharmacology method to predict the active ingredients, potential targets and pathways of Tu-Xian mixture in the treatment of DCI.Methods The potential active ingredients of Tu-xian mixture were obtained by querying databases such as TCMSP, drug targets were screened through Pharmmapper, ETCM, and UniProt databases, and disease target protein groups were collected using TTD, OMIM, and CTD databases. Therapeutic targets were obtained by comparative analysis. Then use WebGestalt to complete GO enrichment analysis and KEGG pathway analysis.Results A total of 51 active ingredients and 619 potential targets were obtained, among which there were 33 key targets for diabetes and 18 key targets for cognitive impairment. After GO analysis and KEGG pathway analysis, steroid hormone biosynthesis and γ-aminobutyric acid signaling pathway may be the important metabolic pathways for Tu-Xian mixture to perform therapeutic effects.Conclusions This work promoted the comprehension of Tu-Xian mixture in the treatment of DCI, and further experimental verification of the prediction results was still needed to support its clinical application.

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Alpha-asarone improves cognitive function of aged rats by alleviating neuronal excitotoxicity via GABAA receptors

Cited by 25 publications

References 49 publications

GABAergic Inhibitory Interneuron Deficits in Alzheimer’s Disease: Implications for Treatment

GABAergic Inhibitory Interneuron Deficits in Alzheimer’s Disease: Implications for Treatment

The PERK-Dependent Molecular Mechanisms as a Novel Therapeutic Target for Neurodegenerative Diseases

Network Pharmacology Dissection of Multi-scale Mechanisms of Action of Tu-Xian Mixture for the Treatment of Diabetic Cognitive Impairment

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