The smell you love so much can actually promote nerve regeneration?

Compiled by: Gong Zixin

Known for its rich, earthy scent, waxy petals, and brilliant white color contrasting with its dark green leaves, the gardenia has long been prized by herbalists, food and fabric dyers, and pharmaceutical companies.

Familial dysautonomia is a rare genetic disease caused by a gene mutation that affects the development and survival of peripheral neurons. Recently, a collaborative team of scientists from several research centers in the United States found that a compound called "genipin" extracted from the Gardenia plant "Horn Jasmine" can promote nerve regeneration. Neurons that were damaged and stunted due to the disease were reborn after being exposed to this plant-derived compound in the laboratory.

"Familial dysautonomia is a devastating disease caused by homozygous point mutations in the ELP1 gene," Dr. Kenya Saito-Diaz wrote in the studies, published in Science Translational Medicine. "Familial dysautonomia specifically affects development and causes degeneration of the peripheral nervous system."

The central nervous system is made up of the brain and spinal cord, while the peripheral nervous system is made up of all the nerves that branch out from the spinal cord and extend to every part of the body. Familial dysautonomia affects the development and survival of the nervous system, including autonomic and sensory neurons. In affected patients, these critical nerve cells do not develop properly and degenerate over time, leading to severe neurological and cardiac symptoms.

Familial dysautonomia initially affects breathing, regulation of body temperature, blood pressure and the ability to form tears. As the disease progresses, patients may experience abnormal heart rhythms, spinal curvature, an inability to feel pain, decreased vision, poor breathing control (especially during sleep) and an increased susceptibility to lung infections. Doctors say a range of other serious symptoms have also been associated with the condition. So far, genipen has only been tested in lab dishes and animal models, but the compound appears to be able to combat key features of the inherited disease. Currently, doctors have no treatments for patients with familial dysautonomia, reports Saito-Diaz, a regenerative medicine researcher at the Center for Molecular Medicine at the University of Georgia in Athens. And the findings so far suggest that the team may be on to a potential treatment.

"Finding treatments that affect nerve growth is a global research priority, not only for familial dysautonomia, but also because a large portion of the world's population suffers from neurodegeneration or peripheral nerve damage. Despite this, there are still major gaps in the knowledge of the development and degeneration of the human peripheral nervous system." Saito-Diaz and colleagues stumbled upon genipin, derived from the fruit of the gardenia flower, while screening a library of 640 compounds for candidate compounds that could protect sensory neurons from degeneration. In the lab, the team found that when neurons were exposed to genipin, it did not cause cell death. In laboratory dishes, the compound not only restored normal development of sensory neurons in patients with familial dysautonomia, but also prevented the cells from early degeneration. Genipin also improved peripheral nerve formation in two mouse models of familial dysautonomia. The team hypothesized that genipin's therapeutic effects are related to the compound's ability to promote cross-linking of the extracellular matrix.

Most importantly, the team found that when genipin was added to cultured nerve cells, it promoted the regrowth of severed axons into healthy sensory and cortical neurons.

"These results make genipin an interesting compound for future applications in nerve regeneration in the peripheral nervous system and possibly in preventing peripheral neuropathy," concludes Saito-Diaz. Meanwhile, compounds derived from gardenia have a long and storied role in folk and traditional medicine. For centuries, traditional Chinese healers have used gardenia as a source of medicinal compounds for depression, inflammation and insomnia. Gardenia has also long been prized by the Chinese for the yellow dye in its seeds.

In the 1980s, Japanese scientists discovered a blue dye derived from the fruit, which is also produced from the gardenia family of flowering shrubs that includes the common gardenia, Cape jasmine and Augusta gardenia, among others.

The isolation of the blue dye paved the way for a host of exciting discoveries, including that genipins, chemically iridoid glycosides, are used to improve the texture and shelf life of certain foods and are being studied as anticancer drugs due to their ability to promote apoptosis, also known as programmed cell death.