Ursolic acid restored the myelin sheath of neurons in mice with multiple sclerosis

Ursolic acid when ingested stops the development of an analogue of multiple sclerosis in mice, stimulates the maturation of oligodendrocytes and restores the myelin sheath of neurons in the Central nervous system. The acid interacts with proliferating peroxisome activated receptor gamma and via transcription factor CREB triggers the secretion of ciliary neurotrophic factor on differentiation of oligodendrocyte precursors. A study published in the journal Proceedings of the National Academy of Sciences.

Multiple sclerosis is an autoimmune disease that disrupts the myelin sheath of neurons throughout the Central nervous system. Modern approaches to the treatment of multiple sclerosis allow to stop the autoimmune reaction and effective in the early stages of the disease. However, there is no way to restore the myelin sheath of nerve cells and return them to functionality. The potential is there — in the demyelination accumulate precursors of oligodendrocytes (the cells that create the sheath of the neurons in the Central nervous system), but they do not develop.

Ursolic acid is found in many plants, including in the rind of the fruit. This substance has a range of pharmacological properties, it is used in the composition of the medicinal plants for the treatment of Parkinson’s disease, rheumatoid arthritis and diabetes. Introduction ursolic acid is also able to prevent the development of experimental autoimmune encephalomyelitis (EAE, a model of multiple sclerosis in mice).

Scientists from China and the United States headed by yuan Zhang (Yuan Zhang) from Thomas Jefferson University investigated the effect of ursolic acid on mice with EAE. The substance was administered orally, therapy started at the beginning of the development of the disease (11 days after starting the development of EAE), is at it’s peak (18 days) or chronic phase (60 days). 30 or 120 day got the spinal cord sections of mice and immunohistochemically stained them razlichnye markers (e.g., myelin, axons, oligodendrocytes).

To share antibacterially and milimetersi effects of ursolic acid, its effect was studied on mice, the destruction of myelin in the brain which was launched by cuprizone — in this case, inflammatory processes and the presence of T-cell immunity in the lesion is minimal. In addition, the effects of ursolic acid were tested on cultures of astrocytes — these cells secrete factors for the development of oligodendrocytes.

All studies described above were also conducted on animals, heterozygous for gene proliferation peroxisome activated receptor gamma (Ppary). Ursolic acid is an agonist of this receptor, and its activation soothes inflammation and triggers the protection mechanisms of neurons. The authors suggested that the interaction with Ppary is the main mechanism of action of ursolic acid.

Most effective dose of ursolic acid was the dose to 25 milligrams per kilogram of body weight per day. The drug significantly reduced the inflammation (p < 0.01) and demyelination (p < 0.001) in the brain, and infiltration of leukocytes (cells Th1 and Th17) in the affected area (p < 0.001). Acid suppressed EAE even when the treatment was started at the peak of development of the disease or in its chronic phase.

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