{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T17:16:38Z","timestamp":1787850998169,"version":"build-2784847793"},"reference-count":30,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,29]],"date-time":"2021-12-29T00:00:00Z","timestamp":1640736000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81803856"],"award-info":[{"award-number":["81803856"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Traumatic nerve injury activates cell stress pathways, resulting in neuronal death and loss of vital neural functions. To date, there are no available neuroprotectants for the treatment of traumatic neural injuries. Here, we studied three important flavanones of citrus components, in vitro and in vivo, to reveal their roles in inhibiting the JNK (c-Jun N-terminal kinase)-JUN pathway and their neuroprotective effects in the optic nerve crush injury model, a kind of traumatic nerve injury in the central nervous system. Results showed that both neural injury in vivo and cell stress in vitro activated the JNK-JUN pathway and increased JUN phosphorylation. We also demonstrated that naringenin treatment completely inhibited stress-induced JUN phosphorylation in cultured cells, whereas nobiletin and hesperidin only partially inhibited JUN phosphorylation. Neuroprotection studies in optic nerve crush injury mouse models revealed that naringenin treatment increased the survival of retinal ganglion cells after traumatic optic nerve injury, while the other two components had no neuroprotective effect. The neuroprotection effect of naringenin was due to the inhibition of JUN phosphorylation in crush-injured retinal ganglion cells. Therefore, the citrus component naringenin provides neuroprotection through the inhibition of the JNK-JUN pathway by inhibiting JUN phosphorylation, indicating the potential application of citrus chemical components in the clinical therapy of traumatic optic nerve injuries.<\/jats:p>","DOI":"10.3390\/ijms23010385","type":"journal-article","created":{"date-parts":[[2021,12,29]],"date-time":"2021-12-29T23:31:35Z","timestamp":1640820695000},"page":"385","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Citrus Naringenin Increases Neuron Survival in Optic Nerve Crush Injury Model by Inhibiting JNK-JUN Pathway"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5388-7993","authenticated-orcid":false,"given":"Jie","family":"Chen","sequence":"first","affiliation":[{"name":"Beijing Advanced Innovation Center for Intelligent Robots and Systems, Beijing Institute of Technology, Beijing 100081, China"},{"name":"School of Life Sciences, Peking University, Beijing 100871, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changming","family":"Yang","sequence":"additional","affiliation":[{"name":"Beijing Advanced Innovation Center for Intelligent Robots and Systems, Beijing Institute of Technology, Beijing 100081, China"},{"name":"School of Mechatronical Engineering, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinjia","family":"He","sequence":"additional","affiliation":[{"name":"Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuo","family":"Arai","sequence":"additional","affiliation":[{"name":"Beijing Advanced Innovation Center for Intelligent Robots and Systems, Beijing Institute of Technology, Beijing 100081, China"},{"name":"School of Mechatronical Engineering, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Huang","sequence":"additional","affiliation":[{"name":"Beijing Advanced Innovation Center for Intelligent Robots and Systems, Beijing Institute of Technology, Beijing 100081, China"},{"name":"School of Mechatronical Engineering, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7424-6829","authenticated-orcid":false,"given":"Xiaodong","family":"Liu","sequence":"additional","affiliation":[{"name":"Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1489-0548","authenticated-orcid":false,"given":"Linqing","family":"Miao","sequence":"additional","affiliation":[{"name":"Beijing Advanced Innovation Center for Intelligent Robots and Systems, Beijing Institute of Technology, Beijing 100081, China"},{"name":"School of Mechatronical Engineering, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e13965","DOI":"10.1097\/MD.0000000000013965","article-title":"Herbal medicine (zhishi xiebai guizhi decoction) for unstable angina: Protocol for a systematic review and meta-analysis","volume":"97","author":"Tang","year":"2018","journal-title":"Medicine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/S2221-1691(13)60079-9","article-title":"Cardioprotective and hepatoprotective effects of Citrus hystrix peels extract on rats model","volume":"3","author":"Putri","year":"2013","journal-title":"Asian Pac. 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