2. Academic Validation
  3. Anemoside A3 ameliorates experimental autoimmune encephalomyelitis by modulating T helper 17 cell response

Anemoside A3 ameliorates experimental autoimmune encephalomyelitis by modulating T helper 17 cell response

  • PLoS One. 2017 Jul 31;12(7):e0182069. doi: 10.1371/journal.pone.0182069.
Fanny C F Ip 1 2 3 4 5,  Yu Pong Ng 1 2 3,  Terry C T Or 1 2 3,  Peiran Sun 1 2 3,  Guangmiao Fu 1 2 3,  Jessica Y H Li 1,  Wen-Cai Ye 5 6 7,  Tom H Cheung 1 2 3,  Nancy Y Ip 1 2 3 4 5
Affiliations

Affiliations

  • 1 Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
  • 2 Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
  • 3 State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
  • 4 Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development, HKUST Shenzhen Research Institute, Shenzhen, Guangdong, China.
  • 5 HKUST-Jinan Joint Laboratory of Innovative Drug Discovery, Jinan University, Guangzhou, China.
  • 6 Institute of Traditional Chinese Medicine and Natural Products College of Pharmacy, Jinan University, Guangzhou, China.
  • 7 Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, Jinan University, Guangzhou, China.
PMID: 28759648 DOI: 10.1371/journal.pone.0182069
Abstract

Anemoside A3 (AA3) is a natural triterpenoid glycoside isolated from the root of Pulsatilla chinensis (Bunge) Regel. We previously showed that AA3 exhibits cognitive-enhancing and neuroprotective properties. In the present study, we demonstrated that AA3 modulates inflammatory responses by regulating prostaglandin E receptor 4 signaling. Because prostaglandin E receptor 4 is involved in the pathophysiology of experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS), we assessed the beneficial effect of AA3 in EAE mice. AA3 treatment significantly reduced clinical severity and inflammatory infiltrates in the spinal cord of EAE mice. In vitro studies revealed that AA3 inhibited the T cell response toward the encephalitogenic epitope of myelin oligodendrocyte glycoprotein (MOG). AA3 significantly downregulated the expressions of certain Th1 and Th17 cytokines in activated T cells re-stimulated by MOG. Moreover, AA3 inhibited the activation of STAT4 and STAT3, which are the transcription factors pivotal for Th1 and Th17 lineage differentiation, respectively, in activated T cells. Pharmacological analysis further suggested that AA3 reduced Th17 cell differentiation and expansion. In conclusion, AA3 exerts an immunomodulatory effect in EAE, demonstrating its potential as a therapeutic agent for MS in humans.

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