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1-Methyl-4-propan-2-ylbenzene from Thymus vulgaris Attenuates Cholinergic Dysfunction

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Abstract

Cholinergic dysfunction is manifested in a plethora of neurodegenerative and psychiatric disorders such as Alzheimer’s, Parkinson’s, and Huntington’s diseases. The extent of cholinergic affliction is maximum in Alzheimer’s disease which is a progressive neurodegenerative disorder involving death of cholinergic neurons. To this date, the therapeutic management of cholinergic dysfunction is limited to provide symptomatic relief through the use of acetylcholinesterase (Ache) inhibitors only. The present study elaborates the potential of thyme oil and its individual components in curtailing cholinergic deficits. We found that thyme oil augments neurotransmission by modulating synaptic acetylcholine (Ach) levels and nicotinic acetylcholine receptor activity, being orchestrated through upregulation of genes cho-1, unc-17 and unc-50. Studies on individual components revealed para-cymene (1-methyl-4-propan-2-ylbenzene) as the active component of thyme oil, contributing its effects through upregulation of cho-1, cha-1, unc-17 and unc-50, while downregulating ace-1 and ace-2. Interestingly, thymol and gamma-terpinene which although were devoid of any activity individually, exhibited significantly enhanced synaptic Ach levels and nicotinic acetylcholine receptor (nAchR) responsiveness, when administered in combination. Our findings advocate thyme oil and its constituents as potential candidates for amelioration of cholinergic dysfunction. The study is speculated to make a way for a new line of “phytomolecules-based drugs” from the diverse pool of natural compounds.

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Abbreviations

Ach:

Acetylcholine

Ache:

Acetylcholinesterase

nAchR:

Nicotinic acetylcholine receptor

T:

Thymol (5-methyl-2-propan-2-ylphenol)

GT:

Gamma-terpinene (1-methyl-4-propan-2-ylcyclohexa-1,4-diene)

PC:

Para-cymene (1-methyl-4-propan-2-ylbenzene)

qPCR:

Qualitative polymerase chain reaction

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Acknowledgment

Authors are highly grateful to Director CSIR-CIMAP, Lucknow for his encouragement. Nematode strains employed in this study were provided by the C.elegans Genetics Center (CGC), University of Minnesota, MN, USA, funded by the NIH National Center for Research Resources (NCRR). We are also thankful to CSIR, New Delhi, for providing vital monetary support under the project–BSC-0117.

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Correspondence to Rakesh Pandey.

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Sammi, S.R., Trivedi, S., Rath, S.K. et al. 1-Methyl-4-propan-2-ylbenzene from Thymus vulgaris Attenuates Cholinergic Dysfunction. Mol Neurobiol 54, 5468–5481 (2017). https://doi.org/10.1007/s12035-016-0083-0

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