Natural compounds in flowers block the activity of enzymes linked to multiple sclerosis and cancer

Structure of flavonoids extracted from dahlia and coreopsis flowers. Red boxes indicate similarities between compound structures and sulfretin (A), and blue boxes indicate differences. Credit: Journal of Biological Chemistry (2024). DOI: 10.1016/j.jbc.2024.107916
Scientists have identified a natural compound that halts processes involved in the development of certain forms of cancer and demyelinating conditions, such as multiple sclerosis, that damage the sheaths surrounding neurons known as myelin.
A study published in the Journal of Biological Chemistry found that a plant-based flavonoid called sulfretin blocks the activity of enzymes involved in MS and cancer.
The discovery was made in cells tested in a lab at Oregon Health & Science University. The next step is to test the compound in animal models to confirm its efficacy and possible side effects in treating neurodegenerative conditions such as cancer and MS.
“We think this is a drug that has the potential to impact a variety of fields,” said Dr. Larry Sherman, professor in the Department of Neuroscience at OHSU Oregon National Primate Research Center.
Researchers found that sulfretin, along with a pair of synthetic compounds that were also tested in living cells, inhibited the activity of a particular type of enzyme known as hyaluronidase, which naturally breaks down hyaluronic acid. This is important because when hyaluronic acid breaks down into fragments, it is known to cause problems in at least two ways.
Pre-myelin repair: Prevents the maturation of oligodendrocytes, the cells that produce myelin. Myelin is a protective sheath that surrounds each nerve cell’s axon (the thread-like part of the cell that transmits electrical signals between cells). Myelin damage is associated with multiple sclerosis, stroke, brain injury, and some types of dementia. Additionally, delayed myelination affects premature infants and can lead to brain damage and cerebral palsy.
Allows cancer cells to proliferate: In cancerous tumors, hyaluronidase activity can allow cancer cells to proliferate unchecked by normal cell death. “Now we have inhibitors that can actually block it,” said Professor Sherman, who is also a professor of cell biology, developmental biology, and cancer biology in the OHSU School of Medicine.
The new research focuses on inhibiting a specific type of hyaluronidase known as cell migration-inducing hyaluronan-binding protein (CEMIP).
In addition to MS and cancer, CEMIP has also been implicated in a variety of disorders, including osteoarthritis, skin infections, brain damage from heavy alcohol use, and even other neurodevelopmental disorders including Alzheimer’s disease. It is thought that. This study shows that its activity appears to be inhibited by sulfretin.
flower molecule
The discovery comes after undergraduate students spent years painstakingly screening plant compounds in the lab of co-author Dr. Angela Hoffman, a longtime and now retired chemistry professor at the University of Portland. Obtained.
“For years, her students have been crushing these flowers, extracting molecules, and testing whether those molecules inhibit hyaluronidase activity,” Professor Sherman said. “Finally, a few years ago, they discovered a promising compound.”
Alec Peters, a graduate student in OHSU’s Sherman lab, discovered that the compound blocks CEMIP activity in tumor cell lines and oligodendrocyte progenitor cells. Oligodendrocytes produce myelin.
Hoffman, a nun and chemistry professor who retired earlier this year from the University of Portland, where she led the convent for 35 years, began working with Sherman 10 years ago. During that time, she said, hundreds of undergraduate students broke down dozens of plants to their molecular essence and worked on tests to see if any of the compounds worked to neutralize CEMIP.
She said this new publication is a testament to the students’ years of diligent research.
“Teaching students to do this type of research will help them in their careers,” Hoffman says. “This discovery could be useful for Alzheimer’s disease and other neurodegenerative diseases. As long as the underlying problem is related to the breakdown of hyaluronic acid, this could be useful for people.”
Further information: Alec Peters et al, “Distinct Chemical Structureshibit the CEMIP hyalronidase and promote oligodendrocyte progenitor cell maturation”, Journal of Biological Chemistry (2024). DOI: 10.1016/j.jbc.2024.107916
Provided by Oregon Health & Science University
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