Natural Product Hederagenin: A Breakthrough in Pain Regulation Research

A recent breakthrough in pain research brings hope to chronic pain patients. A team led by Prof. Dr. Annette Beck-Sickinger at the Institute of Biochemistry, Leipzig University, has uncovered the potential of a natural compound, hederagenin, found in the medicinal plant ivy (Hedera helix), as a highly selective inhibitor of the neuropeptide FF receptor 1 (NPFFR1). This discovery, published in the prestigious journal Angewandte Chemie International Edition, marks a significant stride toward innovative pain therapy solutions. 

Understanding the Role of NPFFR1 in Pain Regulation

NPFFR1 is part of the G protein-coupled receptor (GPCR) family, a critical component in the human body’s signal transduction processes. This receptor is predominantly located in the spinal cord and specific brain areas responsible for pain perception. Scientists have long sought methods to block NPFFR1, as inhibiting this receptor could lead to effective treatments for chronic pain. However, challenges arose due to the receptor’s close similarity to other proteins within the GPCR family.

Hederagenin: A Natural Solution

The research team, in collaboration with Prof. Dr. Michael Schaefer from the Faculty of Medicine, tested thousands of substances using a robust pharmacology screening platform. Among these, hederagenin, a compound derived from ivy, emerged as a highly effective and selective antagonist for NPFFR1. This finding was validated through in vitro studies and sophisticated computer modeling performed by Prof. Dr. Jens Meiler’s group at the Institute of Drug Development.

These studies revealed the binding mode of hederagenin, shedding light on its mechanism as a selective antagonist. This knowledge could pave the way for designing future therapeutics to treat pain conditions with precision.

The Importance of Collaborative Research

The success of this study highlights the value of basic research and interdisciplinary collaboration. The work was conducted within the framework of the Collaborative Research Centre 1423, focusing on the structural dynamics of GPCR activation and signaling. According to Prof. Dr. Beck-Sickinger, “These findings contribute significantly to the understanding of the activation mechanism of NPFFR1 and may facilitate the rational design of future therapeutics for chronic pain.”

A Step Forward in Pain Therapy

Hederagenin’s discovery reinforces the importance of leveraging natural compounds in drug development. Ivy extracts have been historically recognized for their antispasmodic and analgesic properties in phytomedicine, and this research builds on that legacy to offer modern medical solutions.

Hederagenin: A New Frontier in Pain Management

This groundbreaking study exemplifies how basic research can lead to applications with transformative potential:

• Researchers are closer to developing targeted therapies for chronic pain by understanding NPFFR1 activation and inhibition mechanisms.
• The discovery of hederagenin expands knowledge about pain regulation

People all over the world continue to live with excruciating chronic pain. With the Hederagenin discovery, scientists are given the power to create technologically advanced and safer medicines for persistent pain.

Original Publication
Hannah Lentschat, Fabian Liessmann, Claiborne Tydings, Dr. Tina Schermeng, Dr. Jan Stichel, Nicole Urban, Prof. Dr. Michael Schaefer, Prof. Dr. Jens Meiler, Prof. Dr. Annette G. Beck-Sickinger
Journal: Angewandte Chemie (Wiley Online Library)
Article Title: Hederagenin is a Highly Selective Antagonist of the Neuropeptide FF Receptor 1 that Reveals Mechanisms for Subtype Selectivity
Article Publication Date: 06-Dec-2024
DOI: https://doi.org/10.1002/anie.202417786

More Information
https://research.uni-leipzig.de/sfb1423/

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