Experts from the University of South Florida School of Medicine found the compound fenchol in thyme can reduce neurotoxicity in the brain.
In a report in the journal Frontiers in Aging Neuroscience on October 5, the team led by Dr Hariom Yadav reported that fenchol acts similarly to the intestinal-derived SCFA metabolite in reducing amyloid- beta (Aβ), a toxic protein that accumulates in the brain causing memory loss.
SCFAs are short-chain fatty acids produced by beneficial bacteria that provide the main source of nutrients for cells in the large intestine and contribute to improved brain health. Scientists have long recognized that the decline in SCFAs in the elderly is often associated with the neurodegenerative disease Alzheimer’s disease, but its specific causes and effects remain poorly understood.
“SCFAs from the gut that travel through the bloodstream to the brain can bind to and activate free fatty acid receptor 2 (FFAR2), a signaling molecule expressed on neurons. Our study is the first to uncover found that stimulation of FFAR2 sensing by SCFAs may be beneficial in protecting brain cells against the accumulation of Aβ associated with Alzheimer’s disease,” emphasized Yadav.
The hallmark pathology of Alzheimer’s disease is the accumulation of two proteins. One is Aβ, which causes plaques, and the other is the tau protein, which creates plexuses inside brain cells. These two proteins contribute to the loss and death of neurons, ultimately causing a decline in memory, thinking skills, and other cognitive abilities.
Dr. Yadav and his colleagues delve into the molecular mechanisms to explain how interactions between the gut microbiome and the brain can influence brain health and the associated cognitive decline. related to age. This study sets out to explore the “previously unknown” function of FFAR2 in the brain.
Yadav showed for the first time that inhibition of the FFAR2 receptor, which leads to the blocking of its ability to sense SCFAs in the environment outside the neuron and signal transduction inside the cell, contributes to abnormal accumulation. of the Aβ protein, causing Alzheimer’s-associated neurotoxicity.
They then screened more than 144,000 natural compounds to find potential candidates that could mimic the beneficial effects of SCFAs in activating FFAR2 signaling. Dr Yadav notes that it is important to identify a natural compound that substitutes for SCFAs to optimally target the FFAR2 receptor on neurons, as cells in the gut and other organs consume it. absorbs most of this microbial metabolite before they reach the brain via the bloodstream.
The team eventually found that the compound fenchol, which gives thyme its aroma, was best able to bind to FFAR2 to stimulate its signaling.
Further experiments in human neuronal cultures, as well as the nematode worm Caenorhabditis elegans and mice with Alzheimer’s disease demonstrated that fenchol significantly reduces excess Aβ accumulation by stimulating FFAR2 signaling. microbial sensing. Upon closer examination of how fenchol regulates Aβ-induced neurotoxicity, the team found that the compound reduced the number of senile neurons, also known as “zombie” cells, that normally found in the brains of Alzheimer’s patients.
Zombie cells stop regenerating and slowly die. They accumulate in diseased and aging organs, creating a harmful inflammatory environment and sending stress or death signals to neighboring healthy cells. Finally, healthy cells also transform into zombie cells.
“Fenchol actually affects two mechanisms related to aging and proteolysis. It reduces the formation of zombie neurons, while also stimulating the degradation of Aβ and thus the mined amyloid protein. cleared from the brain much faster,” Yadav explains.
Even so, Yadav notes that more human studies are needed to evaluate the actual effects of consuming thyme, as well as to find an appropriate approach to treating Alzheimer’s disease.
“An important question is whether fenchol consumed directly from thyme will be more or less biologically active than isolating it and using it in a pill. We also wanted to know whether a single dose Strong fenchol, if delivered by nasal spray, could be a faster option for delivering the compound to the brain,” Yadav added.
