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Br J Pharmacol. 2012 Jul;166(5):1708-23. doi: 10.1111/j.1476-5381.2012.01869.x.
Natural triterpenes modulate immune-inflammatory markers of experimental autoimmune encephalomyelitis: therapeutic implications for multiple sclerosis.
Martín R, Hernández M, Córdova C, Nieto ML.
Source
Instituto de Biología y Genética Molecular, CSIC-Universidad de Valladolid, Spain.
Abstract
BACKGROUND AND PURPOSE:
Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are inflammatory demyelinating diseases that develop as a result of deregulated immune responses causing glial activation and destruction of CNS tissues. Oleanolic acid and erythrodiol are natural triterpenes that display strong anti-inflammatory and immunomodulatory activities. Oleanolic acid beneficially influences the course of established EAE. We now extend our previous observations to erythrodiol and address the efficacy of both compounds to protect against EAE, given under different regimens.
EXPERIMENTAL APPROACH:
The utility of both triterpenes in disease prevention was evaluated at a clinical and molecular level: in vivo through their prophylactic administration to myelin oligodendrocyte protein-immunized C57BL/6 mice, and in vitro through their addition to stimulated-BV2 microglial cells.
KEY RESULTS:
These triterpenes protected against EAE by restricting infiltration of inflammatory cells into the CNS and by preventing blood-brain barrier disruption. Triterpene-pretreated EAE-mice exhibited less leptin secretion, and switched cytokine production towards a Th2/regulatory profile, with lower levels of Th1 and Th17 cytokines and higher expression of Th2 cytokines in both serum and spinal cord. Triterpenes also affected the humoral response causing auto-antibody production inhibition. In vitro, triterpenes inhibited ERK and rS6 phosphorylation and reduced the proliferative response, phagocytic properties and synthesis of proinflammatory mediators induced by the addition of inflammatory stimuli to microglia.
CONCLUSIONS AND IMPLICATIONS:
Both triterpenes restricted the development of the characteristic features of EAE. We envision these natural products as novel helpful tools for intervention in autoimmune and neurodegenerative diseases including MS.
© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
PMID: 22260389 [PubMed - indexed for MEDLINE] PMCID: PMC3419913 [Available on 2013/7/1]

Sci Rep. 2011;1:201. doi: 10.1038/srep00201. Epub 2011 Dec 19.
Triterpenoid modulation of IL-17 and Nrf-2 expression ameliorates neuroinflammation and promotes remyelination in autoimmune encephalomyelitis.
Pareek TK, Belkadi A, Kesavapany S, Zaremba A, Loh SL, Bai L, Cohen ML, Meyer C, Liby KT, Miller RH, Sporn MB, Letterio JJ.
Source
Department of Pediatrics/Division of Pediatric Hematology-Oncology, University Hospitals Case Medical Center and The Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.
Abstract
Inflammatory cytokines and endogenous anti-oxidants are variables affecting disease progression in multiple sclerosis (MS). Here we demonstrate the dual capacity of triterpenoids to simultaneously repress production of IL-17 and other pro-inflammatory mediators while exerting neuroprotective effects directly through Nrf2-dependent induction of anti-oxidant genes. Derivatives of the natural triterpene oleanolic acid, namely CDDO-trifluoroethyl-amide (CDDO-TFEA), completely suppressed disease in a murine model of MS, experimental autoimmune encephalomyelitis (EAE), by inhibiting Th1 and Th17 mRNA and cytokine production. Encephalitogenic T cells recovered from treated mice were hypo-responsive to myelin antigen and failed to adoptively transfer the disease. Microarray analyses showed significant suppression of pro-inflammatory transcripts with concomitant induction of anti-inflammatory genes including Ptgds and Hsd11b1. Finally, triterpenoids induced oligodendrocyte maturation in vitro and enhanced myelin repair in an LPC-induced non-inflammatory model of demyelination in vivo. These results demonstrate the unique potential of triterpenoid derivatives for the treatment of neuroinflammatory disorders such as MS.

Toxicol Appl Pharmacol. 2013 Mar 13;269(1):72-80. doi: 10.1016/j.taap.2013.03.001. [Epub ahead of print]
Oleanolic acid acetate inhibits atopic dermatitis and allergic contact dermatitis in a murine model.
Choi JK, Oh HM, Lee S, Park JW, Khang D, Lee SW, Lee WS, Rho MC, Kim SH.
Source
CMRI, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
Abstract
Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are common allergic and inflammatory skin diseases caused by a combination of eczema, scratching, pruritus, and cutaneous sensitization with allergens. This paper examines whether oleanolic acid acetate (OAA) modulates AD and ACD symptoms by using an existing AD model based on the repeated local exposure of mite extract (Dermatophagoides farinae extract, DFE) and 2,4-dinitrochlorobenzene to the ears of BALB/c mice. In addition, the paper uses a 2,4-dinitrofluorobenzene-sensitized local lymph node assay (LLNA) for the ACD model. The oral administration of OAA over a four-week period attenuated AD symptoms in terms of decreased skin lesions, epidermal thickness, the infiltration of immune cells (CD4+ cells, eosinophils, and mast cells), and serum IgE, IgG2a, and histamine levels. The gene expression of Th1, Th2, Th17, and Th22 cytokines was reduced by OAA in the lymph node and ear tissue, and the LLNA verified that OAA suppressed ACD. The oral administration of OAA over a three-day period attenuated ACD symptoms in terms of ear thickness, lymphocyte proliferation, and serum IgG2a levels. The gene expression of Th1, Th2, and Th17 cytokines was reduced by OAA in the thymus and ear tissue. Finally, to define the underlying mechanism, this paper uses a TNF-α/IFN-γ-activated human keratinocyte (HaCaT) model. OAA inhibited the expression of cytokines and chemokines through the downregulation of NF-κB and MAPKs in HaCaT cells. Taken together, the results indicate that OAA inhibited AD and ACD symptoms, suggesting that OAA may be effective in treating allergic skin disorders.
Copyright © 2013 Elsevier Inc. All rights reserved.
PMID: 23499868 [PubMed - as supplied by publisher]