Ursolic acid, a compound found in some herbs and in the peels of certain fruits, promoted nerve cell repair and restored the myelin sheath covering and protecting nerve endings in a mouse model of multiple sclerosis (MS), a study reported.
Due to its strong anti-inflammatory and immunomodulatory properties, ursolic acid was seen to have “great potential” as a treatment candidate for MS, especially when the disease reaches its chronic, progressive stage, the researchers said.
These findings were reported in the study, “A dual effect of ursolic acid to the treatment of multiple sclerosis through both immunomodulation and direct remyelination,” published in the journal PNAS.
Many medications currently used to manage MS belong to a class of compounds known as immunomodulatory agents. These therapies focus on lowering the activity of the immune system, in an attempt to prevent immune cells from attacking nerve cells.
While quite useful in reducing the inflammation that marks acute phases of MS, these medications have no effect on neurodegeneration, and do not promote the repair of the myelin sheath that is progressively destroyed over the course of the disease. For these reasons, immunomodulatory agents are less suited to patients at a chronic-progressive stage of MS.
“An MS therapy that has both immunomodulatory and neurodegenerative effects would be highly beneficial,” the researchers wrote.
A team led by investigators at Thomas Jefferson University found that ursolic acid, a natural anti-inflammatory compound found in some herbs and fruit peels like apples and prunes, halted neurodegeneration and promoted myelin repair in mice with experimental autoimmune encephalomyelitis (EAE), a disease that mimics MS in humans.
In their experiments, the team treated sick EAE animals with a purified form of ursolic acid.
“Many experiments have looked at mice in the acute phase, when disease is just starting or at the peak. Instead, we tested whether this compound was effective in chronic disease, once there has already been chronic damage to tissues of central nervous system,” Guang-Xian Zhang, PhD, professor of neuroscience at the Sidney Kimmel Medical College at Thomas Jefferson University, and a co-senior study author, said in a press release.
Ursolic acid was administered orally to EAE mice at different doses.
“By administering different doses, we found that 25 mg/kg/d of UA [ursolic acid] is the optimal dose for suppressing EAE severity; this dose was therefore used in all subsequent in vivo [in a living organism] experiments,” the investigators wrote.
To assess the compound’s effectiveness, researchers started treating mice with ursolic acid at a daily dose of 25 mg/kg, 60 days after EAE onset. Treatment lasted for 60 days.
After 20 days of its use, they started noticing the first improvements in animals’ overall condition. Mice that were completely paralyzed and unable to move at the experiment’s start regained their ability to walk, despite still showing signs of weakness.
“It’s not a cure, but if we see a similar response in people, it would represent a significant change in quality of life. And most significantly, it’s a reversal, which we really haven’t seen before with other agents at such a late stage of disease,” Zhang said.
Ursolic acid’s use was also seen to lower the activity of a sub-class of T-helper cells, called Th17, that are one of the main drivers of autoimmunity and inflammation in MS. And it promoted the maturation of oligodendrocytes — the cells that produce myelin.
“This maturation effect is the most crucial,” Zhang said. “Myelin-sheath-making oligodendrocytes are depleted in MS. And the stem cells that produce new oligodendrocytes are dormant and unable to mature. This compound helps activate those stem cells into making new oligodendrocytes, and is likely responsible for the reversal of symptoms we saw.”
“Our data demonstrate that UA [ursolic acid] has great potential as an agent for MS, especially at the chronic-progressive stage, because of its capacity in both immunomodulation and neural repair,” the researchers concluded.
The team is now planning to test the safety of the compound, which is already available as a dietary supplement, to assess its toxicity when used at higher doses.
“There is additional work we must do to test the safety of this compound, ursolic acid” A.M. Rostami, MD, PhD, chair of the department of neurology at the Vickie and Jack Farber Institute for Neuroscience – Jefferson Health, and the study’s other co-senior author, said. “But this is a great new lead for disease treatment.”
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