Neural Regeneration Research ›› 2019, Vol. 14 ›› Issue (9): 1536-1543.doi: 10.4103/1673-5374.255973

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Pretreated Oenanthe Javanica extract increases anti-inflammatory cytokines, attenuates gliosis, and protects hippocampal neurons following transient global cerebral ischemia in gerbils

Joon Ha Park 1 , In Hye Kim 2 , Ji Hyeon Ahn 1 , YooHun Noh 2 , Sung-Su Kim 2 , Tae-Kyeong Lee 3 , Jae-Chul Lee 3 , Bich-Na Shin 4 , Tae Heung Sim 4 , Hyun Sam Lee 4 , Jeong Hwi Cho 5 , In Koo Hwang 6 , Il Jun Kang 7 , Jong Dai Kim 8 , Moo-Ho Won 3   

  1. 1 Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon, Republic of Korea
    2 Famenity Company, Gwacheon, Geyonggi, Republic of Korea
    3 Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon, Republic of Korea
    4 Danchunok Company, Chuncheon, Gangwon, Republic of Korea
    5 Department of Histology, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeollabuk?do, Republic of Korea
    6 Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul, Republic of Korea
    7 Department of Food Science and Nutrition, Hallym University, Chuncheon, Gangwon, Republic of Korea
    8 Division of Food Biotechnology, School of Biotechnology, Kangwon National University, Chuncheon, Gangwon, Republic of Korea
  • Online:2019-09-15 Published:2019-09-15
  • Contact: Moo-Ho Won, DVM, PhD, mhwon@kangwon.ac.kr; Jong Dai Kim, PhD, jongdai@kangwon.ac.kr.
  • Supported by:

    This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2017R1D1A1B03033271, to JDK), and by the Bio-Synergy Research Project (NRF-2018M3A9C4076478, to IJK) of the Ministry of Science, ICT and Future Planning through the National Research Foundation.

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Abstract:

Recently, we have reported that Oenanthe javanica extract (OJE) displays strong neuroprotective effect      against ischemic damage after transient global cerebral ischemia. However, neuroprotective mechanisms of OJE have not been fully identified. Thus, this study investigated the neuroprotection of OJE in the hippocampal CA1 area and its anti-inflammatory activity in gerbils subjected to 5 minutes of transient global cerebral ischemia. We treated the animals by intragastrical injection of OJE (100 and 200 mg/kg) once daily for 1 week prior to transient global cerebral ischemia. Neuroprotection of OJE was observed by immunohistochemistry for neuronal nuclear antigen and histofluorescence staining for Fluoro-Jade B. Immunohistochemistry of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 was done for astrocytosis and microgliosis, respectively. To investigate the neuroprotective mechanisms of OJE, we performed immunohistochemistry of tumor necrosis factor-alpha and interleukin-2 for pro-inflammatory function and interleukin-4 and interleukin-13 for anti-inflammatory function. When we treated the animals by intragastrical administration of 200 mg/kg of OJE, hippocampal CA1 pyramidal neurons were protected from transient global cerebral ischemia and cerebral ischemia-induced gliosis was inhibited in the ischemic hippocampal CA1 area. We also found that interleukin-4 and -13 immunoreactivities were significantly increased in pyramidal neurons of the ischemic CA1 area after OJE pretreatment, and the increased immunoreactivities were sustained in the CA1 pyramidal neurons after transient global cerebral ischemia. However, OJE pretreatment did not increase interleukin-2 and tumor necrosis factor-alpha immunoreactivities in the CA1 pyramidal neurons. Our findings suggest that pretreatment with OJE can protect neurons and attenuate gliosis from transient global cerebral ischemia via increasing expressions of interleukin-4 and -13. The experimental plan of this study was reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) in Kangwon National University (approval No. KW-160802-1) on August 10, 2016.

Key words: Oenanthe javanica extract, transient global cerebral ischemia, hippocampus, ischemic damage, cerebral ischemia, neuroprotection, glial activation, pro-inflammatory cytokines, anti-inflammatory cytokines, inflammation, neural regeneration