beta-elemene and Multiple-Sclerosis

Experimental autoimmune encephalomyelitis (EAE), an animal mode of multiple sclerosis (MS), was previously considered that is mediated by Th1 cells. However, a number of recent studies provided strong evidence that T helper cells that produce interleukin (IL)-17 (Th17) and anti-inflammatory CD4+ Foxp3+ regulatory T cells (Tregs) play a dominant role in the pathogenesis of EAE. β-elemene is a natural antitumor plant drug with the role of multiple target, and it has been found to pass through the blood-brain barrier easily. It also has been strongly implicated as an immune modulatory agent, but the precise mechanisms of its action are largely unknown. In the present study, we mainly investigated the efficacy and mechanism of β-elemene against EAE in vivo and vitro. The treatment of C57 mice with β-elemene significantly delayed the onset of EAE, markedly suppressed MOG-specific T cell proliferation in a dose-dependent manner, dramatically reduced the IL-17, IL-6, IL-23, and RORγt production and induced the Foxp3 expression in both the periphery and the inflamed spinal cord. These findings indicated that β-elemene amelioration EAE was, to a large extent, due to inhibit differentiation and development of Th17 cells depends on down-regulating expression of IL-6, IL-23, RORγt signaling, and promoting expansion in Treg cells. Suggesting it is useful in the control of MS and other Th17 cell-mediated inflammatory diseases.

Topics: Animals; Cell Proliferation; Encephalomyelitis, Autoimmune, Experimental; Female; Glycoproteins; Humans; Mice; Mice, Inbred C57BL; Multiple Sclerosis; Myelin-Oligodendrocyte Glycoprotein; Peptide Fragments; Sesquiterpenes; T-Lymphocytes, Regulatory; Th17 Cells

beta-elemene is a natural antitumor plant drug. Beneficial effects of beta-elemene therapy have been demonstrated in some kinds of tumor clinically. Especially, it has been found to pass through the blood brain barrier easily. Other reports have indicated that immune disorder that appeared in some tumors usually can be seen in demyelinating diseases including multiple sclerosis and experimental autoimmune encephalomyelitis. However, no information regarding the effects of beta-elemene therapy on the T helper cell subsets, Th1 or Th17 cells in experimental autoimmune encephalomyelitis has been found.. We first determined morphologically that beta-elemene therapy markedly suppressed the inflammation in experimental autoimmune encephalomyelitis optic nerve. We then determined the effect in vivo of beta-elemene on Treg cells and Th17 and Th1 cells. We found that beta-elemene treatment modulated immune balance in both the periphery and the inflamed optic nerve by promoting less downregulation in Treg cells, inhibiting Th17 and Th1 polarization.. Taken together, our finding reveals an important new locus where beta-elemene induces substantial protection in experimental autoimmune encephalomyelitis optic nerve through signaling to several critical subsets of immune cells that reside in the peripheral and central nervous system.

Topics: Animals; Disease Progression; Encephalomyelitis, Autoimmune, Experimental; Female; Glycoproteins; Humans; Interferon-gamma; Interleukin-17; Mice; Mice, Inbred C57BL; Multiple Sclerosis; Myelin-Oligodendrocyte Glycoprotein; Optic Nerve; Peptide Fragments; Phytotherapy; Plant Extracts; Sesquiterpenes