Mangiferin reduces stress induced depressive-like behavior and exerts a neuroprotective effect by inhibition of the NLRP3 inflammasome

doi:10.3969/j.issn.1000-1565.2021.03.007

Abstract

Abstract: The therapeutic effect of mangiferin on chronic unpredictability mild stress depression in rats and its mechanism were studied. Rats were randomly given unpredictable stimuli for 6 consecutive weeks to prepare a depression model. The test group was given mangiferin(MGF, 20, 40, 80 mg/kg)one time through gastric perfusion from week 4 to week 6, while the intragastric administration of fluoxetine(Flu, 10 mg/kg, qd)from week4 to week6 was used as a positive control. At the end of the experiment, biochemical analysis, histopathological examination, and expression of inflammasome related proteins were performed on the serum and brain of the rats.The expression of related inflammatory factor protein in serum of rats was detected. MGF had a significant alleviating effect on the rat behavior of CUMS-induced- DOI:10.3969/j.issn.1000-1565.2021.03.007芒果苷通过作用于NLRP3炎症小体发挥抗抑郁和神经保护作用张蕾^1,2,赵国发^1,2,李楠^1,2,乔晓强³,贾友超^1,2(1.河北大学附属医院肿瘤内科河北省肿瘤放化疗机制与规程研究重点实验室,河北保定 071002;2.河北大学医学院,河北保定 071000;3.河北大学药学院河北省药物质量分析控制重点实验室,河北保定 071002)摘要:研究了芒果苷对慢性不可预测性轻度应激抑郁症大鼠的治疗作用以及作用机制.大鼠随机给予不可预测性刺激,连续6周,制备抑郁症模型.实验组在第4至第6周给予芒果苷(MGF,20、40、80 mg/kg)灌胃治疗,氟西汀(Flu,10 mg/kg)灌胃作为阳性对照.实验结束时对大鼠大脑进行生化分析、组织病理学检查以及炎症小体相关蛋白表达,检测大鼠血清中相关炎症因子蛋白的表达.实验表明MGF对慢性不可预测的轻度应激(CUMS)诱导的大鼠抑郁症行为有明显的改善作用;MGF可以抑制CUMS大鼠NLRP3、Caspase-1和ASC蛋白以及mRNA的表达水平;抑制CUMS大鼠血清中相关炎症因子的蛋白表达水平;MGF同时可以降低NLRP3炎症小体的表达水平,缓解CUMS引起的大脑病理损害,对CUMS大鼠引起的脑损伤起到保护作用.关键词:抑郁症;炎症小体;芒果苷;氟西汀中图分类号:R9 文献标志码:A 文章编号:1000-1565(2021)03-0265-08Mangiferin reduces stress induced depressive-like behavior and exerts a neuroprotective effect by inhibition of the NLRP3 inflammasomeZHANG Lei^1,2, ZHAO Guofa^1,2, LI Nan^1,2, QIAO Xiaoqiang³, JIA Youchao^1,2(1.Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy,Department of Medical Oncology,Affiliated Hospital of Hebei University,Baoding 071002,China;2.Medical College,Hebei University,Baoding 071000,China;3.Key Laboratory of Public Health Safety of Hebei Province,College of Pharmaceutical Sciences,Hebei University,Baoding 071002,China)Abstract: The therapeutic effect of mangiferin on chronic unpredictability mild stress depression in rats and its mechanism were studied. Rats were randomly given unpredictable stimuli for 6 consecutive weeks to prepare a depression model. The test group was given mangiferin(MGF, 20, 40, 80 mg/kg)one time through gastric perfusion from week 4 to week 6, while the intragastric administration of fluoxetine(Flu, 10 mg/kg, qd)from week4 to week6 was used as a positive control. At the end of the experiment, biochemical analysis, histopathological examination, and expression of inflammasome related proteins were performed on the serum and brain of the rats.The expression of related inflammatory factor protein in serum of rats was detected. MGF had a significant alleviating effect on the rat behavior of CUMS-induced- 收稿日期:2020-11-20 基金项目:国家自然科学基金面上项目(21675039);河北大学优秀青年科研创新团队项目(605020521007) 第一作者:张蕾(1995—),女,安徽宿州人,河北大学在读硕士研究生,主要从事外泌体研究.E-mail:945344068@qq.com 通信作者:贾友超(1981—),男,满族,河北保定人,河北大学附属医院副教授,博士,主要从事肿瘤基础研究.E-mail: youchaojia@163.com第3期张蕾等:芒果苷通过作用于NLRP3炎症小体发挥抗抑郁和神经保护作用depression model. MGF can inhibit the expression of protein and mRNA in NLRP3, Caspase-1 and ASC in rats induced by CUMS.The expression of inflammatory factors in the serum of rats was significantly reduced. MGF also reduced the pathological damage of the brain caused by CUMS. MGF can relieve CUMS-induced depression behavior in rats, and at the same time can reduce the expression level of NLRP3 inflammasomes, and play a protective effect on brain damage caused by CUMS rats.

Key words: depression, inflammasome, mangiferin, fluoxetine

CLC Number:

ZHANG Lei, ZHAO Guofa, LI Nan, QIAO Xiaoqiang, JIA Youchao. Mangiferin reduces stress induced depressive-like behavior and exerts a neuroprotective effect by inhibition of the NLRP3 inflammasome[J]. Journal of Hebei University(Natural Science Edition), 2021, 41(3): 265-272.

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