1-Methyl-4-propan-2-ylbenzene from Thymus vulgaris Attenuates Cholinergic Dysfunction
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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.
KeywordsC. elegans Acetylcholine Acetylcholinesterase Thyme oil Para-cymene
Nicotinic acetylcholine receptor
Qualitative polymerase chain reaction
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.
Compliance with Ethical Standards
The authors declare that they have no conflict of Interest.
- 9.Mehta M, Adem A, Sabbagh M (2012) New acetylcholinesterase inhibitors for Alzheimer’s disease. Int J Alzheimers Dis Article ID 728983Google Scholar
- 14.Clevenger JF (1928) Apparatus for determination of volatile oils. J Am Pharmaceut Assoc 17:345–349Google Scholar
- 18.Kihara T, Shimohama S (2004) Alzheimer's disease and acetylcholine receptors. Acta Neurobiol Exp (Wars) 64:99–105Google Scholar
- 19.Chaudhaery SS, Roy KK, Shakya N, Saxena G, Sammi SR, Nazir A, Nath C, Saxena AK (2010) Novel carbamates as orally active acetylcholinesterase inhibitors found to improve scopolamine-induced cognition impairment: pharmacophore-based virtual screening, synthesis, and pharmacology. J Med Chem 9:6490–6505CrossRefGoogle Scholar
- 26.Culetto E, Combes D, Fedon Y, Roig A, Toutant JP, Arpagaus M (1999) Structure and promoter activity of the 5' flanking region of ace-1, the gene encoding acetylcholinesterase of class A in Caenorhabditis elegans. J Mol Biol 30:290 951-66Google Scholar