Researchers at the Indian Institute of Technology (IIT) Kanpur in a new study detailed how cholesterol-lowering drugs like Niacin work at a molecular level.
Niacin is known for its ability to raise levels of “good” cholesterol or high-density lipoprotein cholesterol (HDL) in the body while flushing out the “bad” type or low-density lipoprotein cholesterol (LDL). However, it also raises risks of some skin issues.
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“Niacin is a commonly prescribed drug to lower bad cholesterol and triglycerides while increasing good cholesterol. However, in many patients, the drug causes side effects such as skin redness and itching, referred to as a flushing response. This leads to patients stopping their treatment with adverse effects on their cholesterol levels,” said Prof. Arun K. Shukla of the Department of Biological Sciences and Bioengineering, IIT Kanpur, in a statement.
To understand the side effects of Niacin, the team deployed the cutting-edge cryogenic-electron microscopy (cryo-EM) technology. Using the technology, they visualised the key receptor molecule — Hydroxycarboxylic acid receptor 2 (HCA2) — which Niacin and other related drugs activate.
The HCA2, also known as the niacin receptor or GPR109A, regulates fat-related and artery-clogging processes in the human body.
When the receptor gets activated, it can make the blood vessels widen. This explains why Niacin leads to some patients experiencing a red, flushing skin reaction.
The findings, published in the journal Nature Communications will lead to the development of new drugs to lower cholesterol with fewer side effects.
“The visualisation of the receptor molecule GPR109A’s interaction with Niacin at the molecular level lays the groundwork for creating new drugs that maintain efficacy while minimising undesirable reactions. The study results will also help in developing related drugs for cholesterol and drugs for other conditions such as multiple sclerosis,” Prof. Shukla said.
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