Gardenia plants may hold chemical key to regenerating diseased human nerves

Gardenias are known for their rich, earthy fragrance, waxy petals and brilliant white color that contrasts with the deep emerald green of their leaves. The plant has long been prized by herbalists, seekers of food and fabric dyes, and even pharmaceutical companies.

Now, a collaborative team of scientists at several research centers in the United States has found that a compound known as genipin, derived from the gardenia plant called Cape jasmine, can prompt nerve regeneration. Neurons damaged and stunted by disease find new life in the lab when exposed to the plant-derived compound.

The chemical comes from the fruit of this extraordinarily versatile plant. Gardenia shrubs, in general, are native to tropical and subtropical regions of Asia. But the plants are propagated globally by horticulturists and amateur gardeners who are most familiar with the flower’s beauty and the intoxicating scent of their perfume.

Genipin is being studied as a potential treatment for a rare degenerative nervous system disorder that is caused by a gene mutation. The condition is known as familial dysautonomia, which becomes evident during infancy. The hypothesis of this relatively large cadre of regenerative medicine researchers is that genipin from the humble gardenia plant—known scientifically as Gardenia jasminoides—possesses the secret to effective treatment.

“Familial dysautonomia is a devastating disorder caused by a homozygous point mutation in the gene ELP1,” writes Dr. Kenyi Saito-Diaz in a study published in Science Translational Medicine. “Familial dysautonomia specifically affects development and causes degeneration of the peripheral nervous system.”

While the central nervous system is comprised of the brain and spinal cord, the peripheral nervous system is made up of all nerves branching off the spinal cord, extending to every part of the body.

Familial dysautonomia impacts the development and survival of the nervous system, including autonomic and sensory neurons. These critical nerve cells in affected patients don’t develop properly and degenerate over time, leading to serious neurological and cardiac symptoms.

To date, genipen has been tested only in lab dishes and animal models, but the compound appears capable of combating key hallmarks of the inherited condition. Saito-Diaz, a regenerative medicine researcher in the Center for Molecular Medicine at the University of Georgia in Athens, reports that findings so far suggest the team may be on the trail of a potential therapeutic. Currently, doctors have nothing curative to offer familial dysautonomia patients.

Finding a therapeutic that impacts nerve growth is a worldwide research priority, not only for familial dysautonomia, but because a “high percentage of the world’s population suffers from nerve degeneration or peripheral nerve damage,” Saito-Diaz added.

“Despite this, there are major gaps in the knowledge of human peripheral nervous system development and degeneration. Therefore, there are no available treatments,” Saito-Diaz declared.

Familial dysautonomia initially impacts breathing, the regulation of body temperature, blood pressure, and the ability to form tears. As the disease advances, patients can develop abnormal heart rhythms, spinal curvature, an inability to feel pain, vision loss, poor control of breathing, especially during sleep, and a heightened susceptibility to lung infections. A range of other severe symptoms are also associated with the condition, doctors say.

Geneticists at the Cleveland Clinic in Ohio report that, while rare, the condition is most prevalent among people of Ashkenazi Jewish heritage. In the United States, familial dysautonomia is estimated to affect 1 in 10,000 Ashkenazi Jews. In Israel, 1 in 3,700 people are diagnosed with the condition at birth, according to Cleveland Clinic data.

Gardenia-derived compounds, meanwhile, have played a long and storied role in folk and conventional medicine. For centuries, traditional healers in China have turned to gardenia plants as a source of medicinal compounds capable of treating depression, inflammation and insomnia. Gardenia plants were also long prized among the Chinese for the yellow dye from their seeds.

In the 1980s, Japanese scientists discovered a blue dye derived from a fruit, also produced by Gardenia jasminoides plants. The family of flowering shrubs includes the common gardenia, Cape jasmine and Gardenia Augusta, among others.

Isolation of the blue dye paved the way for a series of exciting discoveries, including genipin, which chemically is an iridoid glycoside. The compound is used to improve the texture and shelf life of certain foods. Additionally, it is being studied as a cancer medication because of its ability to prompt apoptosis, also known as programmed cell death.

Saito-Diaz and colleagues discovered genipin serendipitously while screening a library of 640 compounds for candidates that can protect sensory neurons from degeneration. They happened upon genipin, produced by the fruit of Gardenia jasminoides.

In the laboratory, the team found that it wasn’t apoptosis that genipin caused when neurons were exposed to it. In lab dishes, the compound not only restored proper development of sensory neurons from patients with familial dysautonomia, but it also prevented the cells’ early degeneration. Genipin also improved peripheral nerve formation in two mouse models of familial dysautonomia. The team surmised that genipin’s therapeutic effects are tied to the compound’s ability to promote cross-linking in the extracellular matrix.

Most important among its powerful activities, the team of U.S. researchers found that when added to cultures of nerve cells, genipin boosted the regeneration of severed axons into healthy sensory and cortical neurons.

Saito-Diaz and a large team of colleagues from the University of Georgia worked with collaborators at the University of Tennessee; Icahn School of Medicine’s Institute for Regenerative Medicine at The Mount Sinai Hospital; Weill Cornell Medical College, and the Center for Stem Cell Biology at Sloan Kettering Institute, all three in New York City.

These results “make [genipin] an interesting compound for future applications in nerve regeneration in the [peripheral nervous system] and possibly prevention of peripheral neuropathies,” Saito-Diaz concluded.

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