1-Methyl-4-propan-2-ylbenzene from Thymus vulgaris Attenuates Cholinergic Dysfunction.
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.
Department of Microbial Technology and Nematology, CSIR-Central Institute of Medicinal and Aromatic Plants, Near Kukrail Picnic Spot, Lucknow, 226015, India.
Shreesh Raj
SR
Sammi
Department of Microbial Technology and Nematology, CSIR-Central Institute of Medicinal and Aromatic Plants, Near Kukrail Picnic Spot, Lucknow, 226015, India.
Shalini
S
Trivedi
Division of Toxicology, CSIR-Central Drug Research Institute, Lucknow, 226031, India.
Srikanta Kumar
SK
Rath
Department of Process Chemistry, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, India.
Abhishek
A
Nagar
Department of Process Chemistry, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, India.
Sudeep
S
Tandon
Microbiology and Entomology, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, India.
Alok
A
Kalra
Department of Microbial Technology and Nematology, CSIR-Central Institute of Medicinal and Aromatic Plants, Near Kukrail Picnic Spot, Lucknow, 226015, India. r.pandeycimap@gmail.com.
Rakesh
R
Pandey
D000110:Acetylcholinesterase / Q000235:genetics; D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D001555:Benzene Derivatives / Q000494:pharmacology*; D017173:Caenorhabditis elegans; D059329:Cholinergic Neurons / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D011407:Propane / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D046930:Thymus Plant / Q000737:chemistry*
D001555:Benzene Derivatives; D002800:Cholinesterase Inhibitors; D010936:Plant Extracts; D011978:Receptors, Nicotinic; D000110:Acetylcholinesterase; D011407:Propane
Acetylcholine; Acetylcholinesterase; C. elegans; Para-cymene; Thyme oil