A compound derived from Indian tobacco has the potential to ameliorate some symptoms of Alzheimer’s disease, a recent study by a group of Kerala scientists has found.
A study by researchers at the Jubilee Centre for Medical Research, Thrissur, under Kannur University and the Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, has revealed a promising compound named lobeline, extracted from a plant Lobelia inflata, commonly known as ‘Indian tobacco’.
Developing drugs for Alzheimer’s disease is challenging due to its complex pathology. Impaired glutamatergic signalling is considered to be an important cause of neurological and psychiatric disorders.
Prior evidence has suggested phytochemicals, or plant-derived molecules, could play an important role in protecting human health, and studies have shown their use can be effective at managing complex diseases such as Alzheimer’s, says Dileep Vijayan, one of the scientists in the team.
“Lobeline, an alkaloid, was identified as an inhibitor for certain proteins, including cholinesterase and the NMDA receptor. Cholinesterase is an enzyme that breaks down acetylcholine, a neurotransmitter in the brain, while the NMDA receptor is like a gate in the cell membrane, letting charged particles (ions) go in and out,” says Dr. Vijayan.
If one of the two chemicals, similar in structure, sticks to a protein, the other too is more likely to bind with that protein, causing similar effects. The researchers took advantage of this feature (which is known as chemical similarity assisted target fishing) in their study.
“We tested how well lobeline could protect neuronal cells from high levels of glutamate (known as glutamate mediated excitotoxicity), one of the key pathological events in Alzheimer’s disease. Typically, glutamate-mediated excitotoxicity leads to the deterioration of neuronal cells. Our study was conducted in neurons isolated from rat embryo brain. We found lobeline could protect the neurons from this harmful effect caused by too much glutamate,” Dr. Vijayan says.
The team attributed lobeline’s neuroprotection to its ability to block NMDA receptor activity, based on their studies in neuronal cells. Molecular docking and simulations provided detailed insights at the atomic level into the interaction of cholinesterase and NMDR with lobeline. With the help of computational biology, it was discovered that structural modifications to lobeline yielded novel chemical compounds with potential applications against Alzheimer’s, he says.
Remya Chandran and Dileep Vijayan from the Jubilee Centre for Medical Research; Jayadevi Variyar and Sadasivan from the Department of Biotechnology and Microbiology, Kannur University; and R.V. Omkumar, a former scientist at the Rajiv Gandhi Centre for Biotechnology, conducted these experiments.
The team’s findings were published in the journals IUBMB Life and Scientific Reports.
