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In the southwest regions of China, particularly in Guizhou Province, this plant was used as a Miao ethnic medicine to prevent and treat dyspepsia, dysentery, hypoimmunity, and neurasthenia. In the present study, the neuroprotective effect of KF1 was evaluated against N-methyl-D-aspartate (NMDA)-induced neurotoxicity in vivo and in vitro. An NMDA-induced PC12 cell neurotoxicity assay showed that KF1 effectively improved cellular viability, inhibited the release of lactate dehydrogenase (LDH), and reduced cell apoptosis. Furthermore, KF1-treated NMDA-induced excitotoxicity mice displayed a remarkable capacity for improving spatial learning memory in the Y-maze and Morris water maze tests. In addition, KF1 increased the levels of the neurotransmitters 5-hydroxytryptamine, dopamine, and monoamine oxidase and reduced the calcium ion concentration in the hippocampus of mice. Hematoxylin and eosin and Nissl staining indicated that KF1 effectively reduced the impairment of neurons. Furthermore, Western blot assays showed that KF1 decreased NMDAR1 expression. In contrast, the NMDAR2B (NR2B), glutamate receptor (AMPA), TrkB, protein kinase B (AKT), mammalian target of rapamycin (mTOR), PSD95, and synapsin 1 were upregulated in NMDA-induced PC12 cells and an animal model. These results suggest that KF1 has a remarkable protective effect against NMDA-induced neurotoxicity, which is directly related to the regulation of the NMDA receptor and the activation of the \u03b1-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) and BDNF\/AKT\/mTOR signaling pathways.<\/jats:p>","DOI":"10.3390\/ijms232416150","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T05:25:46Z","timestamp":1671427546000},"page":"16150","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Neuroprotection of Kaji-Ichigoside F1 via the BDNF\/Akt\/mTOR Signaling Pathways against NMDA-Induced Neurotoxicity"],"prefix":"10.3390","volume":"23","author":[{"given":"Faju","family":"Chen","sequence":"first","affiliation":[{"name":"School of Basic Medicine, Guizhou Medical University, Guiyang 550025, China"},{"name":"State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China"},{"name":"Engineering Research Center of Natural Product Efficient Utilization in Guizhou, The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550014, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China"},{"name":"Engineering Research Center of Natural Product Efficient Utilization in Guizhou, The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550014, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengli","family":"Jin","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Natural Product Efficient Utilization in Guizhou, The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550014, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liangqun","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China"},{"name":"Engineering Research Center of Natural Product Efficient Utilization in Guizhou, The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550014, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Natural Product Efficient Utilization in Guizhou, The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550014, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China"},{"name":"Engineering Research Center of Natural Product Efficient Utilization in Guizhou, The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550014, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilang","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China"},{"name":"Engineering Research Center of Natural Product Efficient Utilization in Guizhou, The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550014, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China"},{"name":"Engineering Research Center of Natural Product Efficient Utilization in Guizhou, The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550014, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongsheng","family":"Lou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China"},{"name":"Engineering Research Center of Natural Product Efficient Utilization in Guizhou, The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550014, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China"},{"name":"Engineering Research Center of Natural Product Efficient Utilization in Guizhou, The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550014, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0710-4569","authenticated-orcid":false,"given":"Qiji","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China"},{"name":"Engineering Research Center of Natural Product Efficient Utilization in Guizhou, The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550014, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaosheng","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Guizhou Medical University, Guiyang 550025, China"},{"name":"State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China"},{"name":"Engineering Research Center of Natural Product Efficient Utilization in Guizhou, The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550014, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Cao, Y., Li, B., Ismail, N., Smith, K., Li, T., Dai, R., and Deng, Y. 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