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

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 regulatin...

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Main Authors: Fanny C F Ip, Yu Pong Ng, Terry C T Or, Peiran Sun, Guangmiao Fu, Jessica Y H Li, Wen-Cai Ye, Tom H Cheung, Nancy Y Ip
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5536310?pdf=render
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author Fanny C F Ip
Yu Pong Ng
Terry C T Or
Peiran Sun
Guangmiao Fu
Jessica Y H Li
Wen-Cai Ye
Tom H Cheung
Nancy Y Ip
author_facet Fanny C F Ip
Yu Pong Ng
Terry C T Or
Peiran Sun
Guangmiao Fu
Jessica Y H Li
Wen-Cai Ye
Tom H Cheung
Nancy Y Ip
author_sort Fanny C F Ip
collection DOAJ
description 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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spelling doaj.art-f93368bca7e549aa90f0b2917356011c2022-12-22T02:17:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01127e018206910.1371/journal.pone.0182069Anemoside A3 ameliorates experimental autoimmune encephalomyelitis by modulating T helper 17 cell response.Fanny C F IpYu Pong NgTerry C T OrPeiran SunGuangmiao FuJessica Y H LiWen-Cai YeTom H CheungNancy Y IpAnemoside 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.http://europepmc.org/articles/PMC5536310?pdf=render
spellingShingle Fanny C F Ip
Yu Pong Ng
Terry C T Or
Peiran Sun
Guangmiao Fu
Jessica Y H Li
Wen-Cai Ye
Tom H Cheung
Nancy Y Ip
Anemoside A3 ameliorates experimental autoimmune encephalomyelitis by modulating T helper 17 cell response.
PLoS ONE
title Anemoside A3 ameliorates experimental autoimmune encephalomyelitis by modulating T helper 17 cell response.
title_full Anemoside A3 ameliorates experimental autoimmune encephalomyelitis by modulating T helper 17 cell response.
title_fullStr Anemoside A3 ameliorates experimental autoimmune encephalomyelitis by modulating T helper 17 cell response.
title_full_unstemmed Anemoside A3 ameliorates experimental autoimmune encephalomyelitis by modulating T helper 17 cell response.
title_short Anemoside A3 ameliorates experimental autoimmune encephalomyelitis by modulating T helper 17 cell response.
title_sort anemoside a3 ameliorates experimental autoimmune encephalomyelitis by modulating t helper 17 cell response
url http://europepmc.org/articles/PMC5536310?pdf=render
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