Highly Oligomeric Procyanidins Ameliorate Experimental Autoimmune Encephalomyelitis via Suppression of Th1 Immunity

Abstract

Extracts of Jatoba, a South American herb, when injected i.p. into a mouse model of experimental autoimmune encephalomyelitis (EAE), inhibited the aggravation of clinical symptoms. At the same time, production of myelin oligodendrocyte glycoprotein Ag-specific IFN-γ and TNF-α by spleen cells was markedly suppressed. After administration of Jatoba there was minimal evidence of the demyelination that is characteristic of the EAE model. Decreases in clinical scores were observed when Jatoba extracts were injected just before Ag. The purified active compounds are likely to be polyphenols that are absorbable to polyvinylpolypyrrolidone. The active compounds were polymerized polyphenol polymers (procyanidins) and at least five degrees of polymerization were necessary for activity. In addition, extracts of other plant materials containing such procyanidins had similar activity. After administration of highly polymerized procyanidins, there was a decrease in both dendritic and CD4+ T cells. Although macrophages were increased in number, the expression of CD80 and MHC class II molecules was depressed indicating that the macrophages were immature. The results indicate that the suppression of development of EAE by the highly polymerized procyanidins resulted from an inhibition of Th1 and the effects might be associated with depression of Ag-presenting capability.

High-Performance Liquid Chromatographic Purification of Oligomeric Procyanidins, Trimers up to Nonamers, Derived from the Bark of Jatoba (Hymenaea courbaril)

“…We have recently reported that Jatoba bark could alleviate some of the clinical symptoms associated with experimental allergic encephalitis (EAE), an inflammatory demyelinating disease of the central nervous system. 39) We furthermore demonstrated that the active compounds responsible for the biological activity were procyanidins of Jatoba with DP of more than five. The DP value for each oligomer purified by using the present HPLC system corresponds to each mDP value based on thiolysis data.…”

“…The procyanidins from these plants were composed of a variety of flavan-3-ols. 39) In contrast, the profile of Jatoba procyanidins was extremely simple. Furthermore, the interflavanyl linkage was exclusively B-type; an A-type linkage resists thiolysis to give dimeric derivatives 16,18) which were not detected.…”

Epigallocatechin-3-Gallate Ameliorates Experimental Autoimmune Encephalomyelitis by Altering Balance among CD4+ T-Cell Subsets

“…Furthermore, Th17 cells are implicated in this model and in several other autoimmune diseases. Although some autoimmune responses formerly attributed to Th1 cells are now believed to be mediated by Th17 cells, recent studies [5][6][7][8][9] continue to emphasize the importance of Th1 cells in EAE development. In fact, EAE can be induced by transfer of either Th17 or Th1 cells.…”

Oral Administration of Highly Oligomeric Procyanidins of Jatoba Reduces the Severity of Collagen-Induced Arthritis

“…Fr3 was used as HOPC, because this fraction showed the strongest inhibitory activity toward EAE. 19) Thiolysis analysis. To estimate the degree of polymerization of the procyanidins, thiolysis assays were performed by using scaled down versions of previously published methods.…”

“…The inhibitory activity of polyphenols is dependent on their degree of polymerization, so that monomer catechin-like green tea polyphenols do not prevent EAE. 19) However, there are reports that green tea polyphenols can ameliorate CIA. 20) In this study, we examined whether procyanidins purified from Jatoba could inhibit CIA, and whether the inhibitory activity would be dependent on polymerization.…”