Kukoamine A Prevents Radiation-Induced Neuroinflammation and Preserves Hippocampal Neurogenesis in Rats by Inhibiting Activation of NF-κB and AP-1.
Impaired hippocampal neurogenesis and neuroinflammation are involved in the pathogenesis of radiation-induced brain injury. Kukoamine A (KuA) was demonstrated to have neuroprotective effects through inhibiting oxidative stress and apoptosis after whole-brain irradiation (WBI) in rats. The aim of this study was to investigate whether administration of KuA would prevent radiation-induced neuroinflammation and the detrimental effect on hippocampal neurogenesis. For this study, male Wistar rats received either sham irradiation or WBI (30 Gy single dose of X-rays) followed by the immediate injection of either KuA or vehicle intravenously. The dose of KuA was 5, 10, and 20 mg/kg, respectively. The levels of pro-inflammatory cytokines were assayed by ELISA kits. The newborn neurons were detected by 5-bromo-2-deoxyuridine (BrdU)/neuronal nuclei (NeuN) double immunofluorescence. Microglial activation was measured by Iba-1 immunofluorescence. The expression of Cox-2 and the activation of nuclear factor κB (NF-κB), activating protein 1(AP-1), and PPARδ were evaluated by western blot. WBI led to a significant increase in the level of TNF-α, IL-1β, and Cox-2, and it was alleviated by KuA administration. KuA attenuated microglial activation in rat hippocampus after WBI. Neurogenesis impairment induced by WBI was ameliorated by KuA. Additionally, KuA alleviated the increased translocation of NF-κB p65 subunit and phosphorylation of c-jun induced by WBI and elevated the expression of PPARδ. These data indicate that KuA could ameliorate the neuroinflammatory response and protect neurogenesis after WBI, partially through regulating the activation of NF-κB, AP-1, and PPARδ.
School of Life Sciences and Biopharmaceutis, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, People's Republic of China.
Yaqiong
Y
Zhang
Department of Pharmacy, General Hospital of Shenyang Military Area Command, 83 Wenhua Road, Shenyang, Liaoning, 110016, People's Republic of China.
Lingyue
L
Gao
Department of Radiation Oncology, General Hospital of Shenyang Military Area Command, 83 Wenhua Road, Shenyang, Liaoning, 110016, People's Republic of China.
Zhihua
Z
Cheng
School of Life Sciences and Biopharmaceutis, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, People's Republic of China.
Jiayi
J
Cai
Department of Pharmacy, General Hospital of Shenyang Military Area Command, 83 Wenhua Road, Shenyang, Liaoning, 110016, People's Republic of China.
Yixuan
Y
Niu
Department of Pharmacy, General Hospital of Shenyang Military Area Command, 83 Wenhua Road, Shenyang, Liaoning, 110016, People's Republic of China.
Weihong
W
Meng
School of Life Sciences and Biopharmaceutis, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, People's Republic of China. zhaoqingchun1967@163.com.
Qingchun
Q
Zhao
D000818:Animals; D001921:Brain / Q000528:radiation effects; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology / Q000528:radiation effects*; D007249:Inflammation / Q000517:prevention & control*; D008297:Male; D017628:Microglia / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D055495:Neurogenesis / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D047494:PPAR delta / Q000096:biosynthesis; D010766:Phosphorylation / Q000187:drug effects; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000517:prevention & control; D051381:Rats; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D016207:Cytokines; D016328:NF-kappa B; D018696:Neuroprotective Agents; D047494:PPAR delta; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; C096274:kukoamine A; D013096:Spermine; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2
Ionizing radiation; Kukoamine A; Neurogenesis; Neuroinflammation; Radiation-induced brain injury