Naturally occurring hederagenin found to bind to the pain regulation receptor

A team of scientists led by Professor Annette Beck-Sickinger from the Institute of Biochemistry at Leipzig University has made an important advance in pain relief research. They discovered that hederagenin, a naturally occurring substance found in the medicinal plant ivy, binds to the pain regulation receptor. Extracts of ivy (Hedera helix) have antispasmodic and analgesic effects in phytomedicine.

In the search for selective inhibitors of the protein neuropeptide FF receptor 1, which is relevant for human pain regulation, the researchers discovered that hederagenin is well suited for this purpose. They have now published their findings in the journal Angewandte Chemie International Edition.

Neuropeptide FF receptor 1 (NPFFR1) is a G protein-coupled receptor (GPCR) involved in the signaling of various physiological processes in the human body. In recent years, it has been discovered that this protein is mainly found in the spinal cord and in areas of the brain involved in pain perception. Blocking this receptor could help treat chronic pain. This has not been possible until now because NPFFR1 has many similar relatives.

Two scientists from Beck-Sickinger’s research group tested thousands of substances. Michael Schaefer, Professor of Pharmacology at the Faculty of Medicine, provided a screening platform for this purpose. The researchers came across the naturally occurring substance hederagenin.

They characterized the binding mode of the inhibitor in detailed in vitro studies. Computer modeling of the three-dimensional receptor-inhibitor complex by Professor Jens Meiler’s group at the Institute for Drug Discovery confirmed this insight.

“These findings make a significant contribution to understanding the activation mechanism of NPFFR1 and may facilitate the rational design of future therapeutics for chronic pain. They demonstrate the importance of basic research in translating findings into applications,” says Professor Beck-Sickinger.