Astragalus injection ameliorates lipopolysaccharide-induced cognitive decline via relieving acute neuroinflammation and BBB damage and upregulating the BDNF-CREB pathway in mice

作者全名："Liu, Ke; Wan, Guoran; Jiang, Ruhong; Zou, Li; Wan, Dong; Zhu, Huifeng; Feng, Shan"

作者地址："[Liu, Ke; Zou, Li; Zhu, Huifeng; Feng, Shan] Southwest Univ, Coll Pharmaceut Sci & Tradit Chinese Med, Dept Tradit Chinese Med, 2 Tiansheng Rd, Chongqing 400715, Peoples R China; [Wan, Guoran] Chongqing Med Univ, Dept Emergency & Crit Care Med, Affiliated Hosp 1, Chongqing, Peoples R China; [Jiang, Ruhong] Chongqing Med Univ, Dept Psychiat, Clin Coll 1, Chongqing, Peoples R China; [Wan, Dong] Chongqing Med Univ, Dept Gen Practice, Clin Coll 5, Chongqing, Peoples R China"

通信作者："Zhu, HF; Feng, S (通讯作者)，Southwest Univ, Coll Pharmaceut Sci & Tradit Chinese Med, Dept Tradit Chinese Med, 2 Tiansheng Rd, Chongqing 400715, Peoples R China."

来源：PHARMACEUTICAL BIOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000798129200001

JCR分区：Q1

影响因子：3.8

年份：2022

卷号：60

期号：1

开始页：825

结束页：839

文献类型：Article

关键词：Astragaloside IV; TrkB; neurodegeneration; tight junction; post-sepsis cognitive impairment

摘要："Context Post-sepsis cognitive impairment is one of the major sequelae observed in survivors of sepsis. Astragalus injection is the normally preferred treatment in sepsis in clinical settings. Objective This study evaluated the benefits and related mechanism of Astragalus injection on post-sepsis cognitive impairment. Materials and methods C57BL/6J mice were divided into three groups: Control, LPS (2.5 mg/kg, i.p.), and LPS + Astragalus injection (5.0 mL/kg). The surviving mice from sepsis were injected with material named Astragalus injection continuously for 13 days. Behavioural tests were first conducted to evaluate the benefits. Second, inflammatory cytokines secretion, BBB integrity, neurodegeneration, and protein expression was evaluated in vivo and in vitro. Results Compared with the LPS group, mice in Astragalus injection group exhibited shorter escape latency (34.6 s versus 24.5 s) in the Morris water maze test. Treatment with Astragalus injection could reverse LPS-induced neuroinflammation in mice and BV2 cells. Continuous Astragalus injection treatment not only prevented blood-brain barrier dysfunction, but also prevented neurodegeneration. Further molecular docking tests and western blot results reflected that the main constituents of Astragalus injection could interact with TrkB (the estimated binding energy values were -7.0 to -5.0 kcal/mol) and upregulate the protein expression of BDNF/TrkB/CREB signalling pathway during the chronic stage in mice. Discussion Astragalus injection treatment could reduce neuroinflammation, reverse BBB dysfunction, prevent neurodegeneration, and upregulate BDNF-CREB pathway during LPS-induced sepsis, ultimately preventing the development of cognitive decline. Conclusion Astragalus injection could be a potential preventive and therapeutic strategy for sepsis survivors in clinical settings."

基金机构："National Natural Science Foundation of China (NSFC) [NSFC-81903817, 81873034]; Fundamental Research Funds for the Central Universities [XDJK2017D154, XDJK2019C113]"

基金资助正文："This study was funded by National Natural Science Foundation of China (NSFC) [NSFC-81903817 and -81873034]; Fundamental Research Funds for the Central Universities [XDJK2017D154, XDJK2019C113]."