The goal of the study is to find an alternative to commonly used synthetic opioids. Gruber explains the background: “Morphine was one of the first plant-based medicines and was isolated from the dried latex of poppies more than 200 years ago. It binds to opioid receptors in the brain and is still regarded as the main pillar of pain therapy.
But there is high chance of opioid addiction, and an overdose, which can cause respiratory depression and, in the worst case, in death.”
So, researchers throughout the world are trying to make analgesics safer and to find active drug molecules that do not have the typical opioid side-effects.
Sunflower extracts were used in traditional medicine for their anti-inflammatory and analgesic properties. In this study, researchers of Austria and Australia, including Edin, isolated the plant molecule that is responsible for this effect.
Sunflower trypsin inhibitor-1 (SFTI-1) was optimized by ‘grafting’ an endogenous opioid peptide into its scaffold. Around 19 peptides were chemically synthesized based on the original SFTI-1 blueprint and pharmacologically tested.
“One of these variants turned out to be our lead candidate for as potential innovative analgesic molecule, especially for pain in the gastrointestinal tract or in the peripheral organs. This peptide is extremely stable, highly potent and its action is restricted to the body’s periphery.
Its use is therefore expected to produce fewer of the typical side-effects associated with opioids,” point out Gruber and Muratspahi.
It acts by affecting opioid receptor, but is often associated with mood disorders and depression. The sunflower peptide does not act in the brain, hence there is much less risk of dependency or addiction.
It also activates only the molecular signaling pathway that influences pain transmission but does not cause the typical opioid side-effects.
Scientists see great potential for using this peptide in the future to develop a safe medication – which could be administered orally in tablet form – to treat pain in the gastrointestinal tract, and this drug could potentially also be used for related painful conditions, e.g. for inflammatory bowel disease.
The research of this MedUni Vienna laboratory led by Christian Gruber exploits the concept of using Nature’s blueprint to develop optimized drugs.
“We are searching through large databases containing genetic information of plants and animals, decoding new types of peptide molecules and studying their structure, with a view to testing them pharmacologically on enzymes or membrane receptors and ultimately utilizing them in the disease model,” explains Gruber.
Potential drug candidates are synthesized in a modified form based on the natural blueprint, to obtain optimized pharmacological properties.