The AMPK-SIRT1-FoxO1-NF-κB signaling pathway participates in Hesperetin-mediated neuroprotective effects against traumatic brain injury via the NLRP3 inflammasome
机构：[1]Department of Neurosurgery, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.外科科室神经外科神经外一科（神经外科）昆明医科大学附属第一医院[2]Animal Zoology Department, Kunming Medical University, Kunming 650500, China.[3]Institute of Neuroscience, Basic Medical College, Kunming Medical University, No.1168 Chunrong West Road, Yuhua Street, Chenggong District, Kunming 650500, China.
Traumatic brain injury (TBI) induces inflammations that lead to secondary damage. Hesperetin (Hes) exerts anti-inflammatory activities against central nervous system (CNS) diseases. This article probes the possible neuroprotective effect and mechanism of Hes on TBI-induced acute cerebral damage.Male C57BL/6J mice were subjected to controlled cortical impingement (CCI) and Hes (50 mg/kg) treatment after the surgery. Short-term neurological deficits were assessed with the modified neurological severity score (mNSS) and the Rota-rod test. The brain edema was tested by the wet/dry method. Neuron apoptosis was evaluated by Nissl staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. The blood-brain barrier (BBB) integrity was measured by Evans' blue staining, and immunohistochemistry (IHC) was conducted to study BV2 microglial activation. BV2 microglia and HT22 neuronal cells were stimulated by oxygen-glucose deprivation followed by recovery (OGD/R) and processed with Hes. Quantitative real-time-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were implemented to gauge the expression of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-β (IL-1-β) and interleukin-6 (IL-6). Western blot (WB) was performed to check AMPK-SIRT1-FoxO1 both in vitro and in vivo.Hes eased neurological deficits, cerebral edema, and neuronal apoptosis in mice following TBI. Hes hampered microglial activation and pro-inflammatory cytokines production. Hes promoted AMPK and SIRT1 expression, whereas repressed the phosphorylation of FoxO1-NF-κB, and inhibited NLRP3 expression. The AMPK inhibitor Compound C markedly reversed Hes-mediated anti-inflammatory and neuron-protective effects.Hes curbs microglial activation-mediated inflammation via the AMPK-SIRT1-FoxO1-NF-κB axis, thereby improving neurobehavioral function after TBI.
第一作者机构：[1]Department of Neurosurgery, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
共同第一作者：
通讯作者：
通讯机构：[1]Department of Neurosurgery, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.[3]Institute of Neuroscience, Basic Medical College, Kunming Medical University, No.1168 Chunrong West Road, Yuhua Street, Chenggong District, Kunming 650500, China.[*1]Institute of Neuroscience, Basic Medical College, Kunming Medical University, No.1168 Chunrong West Road, Yuhua Street, Chenggong District, Kunming 650500, China[*2]Department of Neurosurgery, First Affiliated Hospital of Kunming Medical University, No.295 Xichang Road, Kunming 650032, China
推荐引用方式(GB/T 7714)：
Song Hai,Ding Zhongyun,Chen Jilin,et al.The AMPK-SIRT1-FoxO1-NF-κB signaling pathway participates in Hesperetin-mediated neuroprotective effects against traumatic brain injury via the NLRP3 inflammasome[J].IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY.2022,44(6):970-983.doi:10.1080/08923973.2022.2096464.
APA：
Song Hai,Ding Zhongyun,Chen Jilin,Chen Tingbao,Wang Tinghua&Huang Jin.(2022).The AMPK-SIRT1-FoxO1-NF-κB signaling pathway participates in Hesperetin-mediated neuroprotective effects against traumatic brain injury via the NLRP3 inflammasome.IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY,44,(6)
MLA：
Song Hai,et al."The AMPK-SIRT1-FoxO1-NF-κB signaling pathway participates in Hesperetin-mediated neuroprotective effects against traumatic brain injury via the NLRP3 inflammasome".IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY 44..6(2022):970-983
