Eupatilin exerts neuroprotective effects in mice with transient focal cerebral ischemia by reducing microglial activation.
Microglial activation and its-driven neuroinflammation are characteristic pathogenetic features of neurodiseases, including focal cerebral ischemia. The Artemisia asiatica (Asteraceae) extract and its active component, eupatilin, are well-known to reduce inflammatory responses. But the therapeutic p...
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0171479&type=printable |
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| author | Arjun Sapkota Bhakta Prasad Gaire Kyu Suk Cho Se Jin Jeon Oh Wook Kwon Dae Sik Jang Sun Yeou Kim Jong Hoon Ryu Ji Woong Choi |
| author_facet | Arjun Sapkota Bhakta Prasad Gaire Kyu Suk Cho Se Jin Jeon Oh Wook Kwon Dae Sik Jang Sun Yeou Kim Jong Hoon Ryu Ji Woong Choi |
| author_sort | Arjun Sapkota |
| collection | DOAJ |
| description | Microglial activation and its-driven neuroinflammation are characteristic pathogenetic features of neurodiseases, including focal cerebral ischemia. The Artemisia asiatica (Asteraceae) extract and its active component, eupatilin, are well-known to reduce inflammatory responses. But the therapeutic potential of eupatilin against focal cerebral ischemia is not known, along with its anti-inflammatory activities on activated microglia. In this study, we investigated the neuroprotective effect of eupatilin on focal cerebral ischemia through its anti-inflammation, particularly on activated microglia, employing a transient middle cerebral artery occlusion/reperfusion (tMCAO), combined with lipopolysaccharide-stimulated BV2 microglia. Eupatilin exerted anti-inflammatory responses in activated BV2 microglia, in which it reduced secretion of well-known inflammatory markers, including nitrite, IL-6, TNF-α, and PGE2, in a concentration-dependent manner. These observed in vitro effects of eupatilin led to in vivo neuroprotection against focal cerebral ischemia. Oral administration of eupatilin (10 mg/kg) in a therapeutic paradigm significantly reduced brain infarction and improved neurological functions in tMCAO-challenged mice. The same benefit was also observed when eupatilin was given even within 5 hours after MCAO induction. In addition, the neuroprotective effects of a single administration of eupatilin (10 mg/kg) immediately after tMCAO challenge persisted up to 3 days after tMCAO. Eupatilin administration reduced the number of Iba1-immunopositive cells across ischemic brain and induced their morphological changes from amoeboid into ramified in the ischemic core, which was accompanied with reduced microglial proliferation in ischemic brain. Eupatilin suppressed NF-κB signaling activities in ischemic brain by reducing IKKα/β phosphorylation, IκBα phosphorylation, and IκBα degradation. Overall, these data indicate that eupatilin is a neuroprotective agent against focal cerebral ischemia through the reduction of microglial activation. |
| format | Article |
| id | doaj-art-c1294dcdbb104ef5b6864f315a5b8df6 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-c1294dcdbb104ef5b6864f315a5b8df62025-08-20T02:03:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01122e017147910.1371/journal.pone.0171479Eupatilin exerts neuroprotective effects in mice with transient focal cerebral ischemia by reducing microglial activation.Arjun SapkotaBhakta Prasad GaireKyu Suk ChoSe Jin JeonOh Wook KwonDae Sik JangSun Yeou KimJong Hoon RyuJi Woong ChoiMicroglial activation and its-driven neuroinflammation are characteristic pathogenetic features of neurodiseases, including focal cerebral ischemia. The Artemisia asiatica (Asteraceae) extract and its active component, eupatilin, are well-known to reduce inflammatory responses. But the therapeutic potential of eupatilin against focal cerebral ischemia is not known, along with its anti-inflammatory activities on activated microglia. In this study, we investigated the neuroprotective effect of eupatilin on focal cerebral ischemia through its anti-inflammation, particularly on activated microglia, employing a transient middle cerebral artery occlusion/reperfusion (tMCAO), combined with lipopolysaccharide-stimulated BV2 microglia. Eupatilin exerted anti-inflammatory responses in activated BV2 microglia, in which it reduced secretion of well-known inflammatory markers, including nitrite, IL-6, TNF-α, and PGE2, in a concentration-dependent manner. These observed in vitro effects of eupatilin led to in vivo neuroprotection against focal cerebral ischemia. Oral administration of eupatilin (10 mg/kg) in a therapeutic paradigm significantly reduced brain infarction and improved neurological functions in tMCAO-challenged mice. The same benefit was also observed when eupatilin was given even within 5 hours after MCAO induction. In addition, the neuroprotective effects of a single administration of eupatilin (10 mg/kg) immediately after tMCAO challenge persisted up to 3 days after tMCAO. Eupatilin administration reduced the number of Iba1-immunopositive cells across ischemic brain and induced their morphological changes from amoeboid into ramified in the ischemic core, which was accompanied with reduced microglial proliferation in ischemic brain. Eupatilin suppressed NF-κB signaling activities in ischemic brain by reducing IKKα/β phosphorylation, IκBα phosphorylation, and IκBα degradation. Overall, these data indicate that eupatilin is a neuroprotective agent against focal cerebral ischemia through the reduction of microglial activation.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0171479&type=printable |
| spellingShingle | Arjun Sapkota Bhakta Prasad Gaire Kyu Suk Cho Se Jin Jeon Oh Wook Kwon Dae Sik Jang Sun Yeou Kim Jong Hoon Ryu Ji Woong Choi Eupatilin exerts neuroprotective effects in mice with transient focal cerebral ischemia by reducing microglial activation. PLoS ONE |
| title | Eupatilin exerts neuroprotective effects in mice with transient focal cerebral ischemia by reducing microglial activation. |
| title_full | Eupatilin exerts neuroprotective effects in mice with transient focal cerebral ischemia by reducing microglial activation. |
| title_fullStr | Eupatilin exerts neuroprotective effects in mice with transient focal cerebral ischemia by reducing microglial activation. |
| title_full_unstemmed | Eupatilin exerts neuroprotective effects in mice with transient focal cerebral ischemia by reducing microglial activation. |
| title_short | Eupatilin exerts neuroprotective effects in mice with transient focal cerebral ischemia by reducing microglial activation. |
| title_sort | eupatilin exerts neuroprotective effects in mice with transient focal cerebral ischemia by reducing microglial activation |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0171479&type=printable |
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