Summary: Anacardic acid, a compound found in cashew shells, promotes the repair of myelin. The findings could have positive implications for the treatment of diseases, such as multiple sclerosis, that are characterized by demyelination.
Source: Vanderbilt University Medical Center
In laboratory experiments, a chemical compound found in the shell of the cashew nut promotes the repair of myelin, a team from Vanderbilt University Medical Center reports today in the Proceedings of the National Academy of Sciences.
“We see this as an exciting finding, suggesting a new avenue in the search for therapies to correct the ravages of MS and other demyelinating diseases,” said the paper’s senior author, Subramaniam Sriram, MBBS, William C. Weaver III Professor of Neurology and chief of the Division of Neuroimmunology.
Previous work led by Sriram showed that a protein called interleukin 33, or IL-33, induced myelin formation. IL-33 is, among other things, an immune response regulator, and multiple sclerosis is an autoimmune disorder.
The cashew shell compound is called anacardic acid. Sriram and team grew interested in it because it’s known to inhibit an enzyme involved in gene expression called histone acetyltransferase, or HAT, and the team had discovered that whatever inhibits HAT induces production of IL-33.
The report includes a range of new findings that point to potential therapeutic use of anacardic acid for demyelinating diseases:
In vitro, the addition of the compound to rat cells most responsible for myelination — oligodendrocyte precursor cells, or OPCs — spurred induction of IL-33 and rapidly increased the expression of myelin genes and proteins, including dose-dependent increases in myelin basic protein;
In two animal models of demyelination, treatment with the compound increased the relative presence of IL-33-expressing OPCs and led to reduced paralysis;
In an animal model of demyelination treated with the compound, dissection and electron microscopy showed dose-dependent increases in myelination.
“These are striking results that clearly urge further study of anarcardic acid for demyelinating diseases,” Sriram said.
Anacardic acid induces IL-33 and promotes remyelination in CNS
Given the known neuroreparative actions of IL-33 in experimental models of central nervous system (CNS) injury, we predicted that compounds which induce IL-33 are likely to promote remyelination. We found anacardic acid as a candidate molecule to serve as a therapeutic agent to promote remyelination. Addition of anacardic acid to cultured oligodendrocyte precursor cells (OPCs) rapidly increased expression of myelin genes and myelin proteins, suggesting a direct induction of genes involved in myelination by anacardic acid. Also, when added to OPCs, anacardic acid resulted in the induction of IL-33. In vivo, treatment of with anacardic acid in doses which ranged from 0.025 mg/kg to 2.5 mg/kg, improved pathologic scores in experimental allergic encephalitis (EAE) and in the cuprizone model of demyelination/remyelination. Electron microscopic studies performed in mice fed with cuprizone and treated with anacardic acid showed lower g-ratio scores when compared to controls, suggesting increased remyelination of axons. In EAE, improvement in paralytic scores was seen when the drug was given prior to or following the onset of paralytic signs. In EAE and in the cuprizone model, areas of myelin loss, which are likely to remyelinate, was associated with a greater recruitment of IL-33–expressing OPCs in mice which received anacardic acid when compared to controls.