Andrographolide triggers autophagy-mediated inflammation inhibition and attenuates chronic unpredictable mild stress (CUMS)-induced depressive-like behavior in mice
Andrographolide triggers autophagy-mediated inflammation inhibition and attenuates chronic unpredictable mild stress (CUMS)-induced depressive-like behavior in mice
复制标题
穿心莲内酯触发自噬介导的炎症抑制并减轻慢性不可预测的轻度应激（CUMS）诱导的小鼠抑郁样行为
DOI：
10.1016/j.taap.2019.114688
复制
发表时间：
2019-09-15
影响因子：
3.8
通讯作者：
Guo, Wenjie
中科院分区：
文献类型：
--
作者：
Geng, Ji;Liu, Jia;Guo, Wenjie
抑郁症是世界上最常见的精神疾病之一。穿心莲内酯是一种天然产物，具有明显的抗炎活性。本研究旨在探讨穿心莲内酯对慢性不可预见性轻度应激（CHMS）诱导的小鼠抑郁样行为的抗抑郁作用。在强迫游泳试验、蔗糖偏好试验、悬尾试验和Y-迷宫等行为试验中，给予穿心莲内酯后，表现有所改善。促炎介质NO和细胞因子IL-1 β、IL-6以及TNF-α使用试剂盒、ELISA和实时PCR测量前额皮质中的促炎介质NO和细胞因子IL-1 β、IL-6以及TNF-α。采用免疫印迹法检测前额叶皮层NF-κ B信号转导、NLRP 3炎性小体组装和自噬过程。观察到5 mg/kg穿心莲内酯治疗明显改善抑郁样行为。此外，5 mg/kg穿心莲内酯治疗还降低了前额叶皮质中促炎介质和细胞因子（NO、考克斯-2、iNOS、IL-1 β、IL-6和TNF-α）、NF-κ B信号传导（p-p65、p-I κ B α）和NLRP 3炎性体组装（NLRP 3、ASC和半胱天冬酶-1）的表达。此外，自噬水平增加后，穿心莲治疗。最后，穿心莲内酯的抗抑郁和抗炎作用被氯喹（CQ）的应用所削弱，这表明穿心莲内酯诱导的自噬主要是通过启动而不是阻断自噬流来影响的。这些结果表明，穿心莲内酯在CNS诱导的小鼠中产生抗抑郁样和抗炎作用，这可能是通过上调自噬介导的。
Depression is one of the most common psychiatric disorders in the world. Andrographolide is a natural product that displays evident anti-inflammatory activities. The purpose of the present study was to explore the anti-depressant potential of andrographolide in chronic unpredictable mild stress (CUMS)-induced depressive-like behavior in mice. Performance in behavioral tests such as the forced swim test, sucrose preference test, tail suspension test and Y-maze was improved following andrographolide administration. The pro-inflammatory mediator NO and cytokines IL-1 beta, IL-6 as well as TNF-alpha were measured in the prefrontal cortex using a reagent kit, ELISA and real-time PCR. NF-kappa B signaling, NLRP3 inflammasome assembly and autophagy process were examined in the prefrontal cortex using western blotting. It was observed that 5 mg/kg andrographolide treatment obviously improved depressive-like behavior. In addition, 5 mg/kg andrographolide treatment also decreased the expression of pro-inflammatory mediators and cytokines (NO, COX-2, iNOS, IL-1 beta, IL-6 and TNF-alpha), NF-kappa B signaling (p-p65, p-I kappa B alpha) and NLRP3 inflammasome assembly (NLRP3, ASC and caspase-1) in the prefrontal cortex. Moreover, autophagy levels increased after andrographolide treatment. Finally, the antidepressant and anti-inflammatory effects of andrographolide were compromised by the application of chloroquine (CQ), which suggested that andrographolide-induced autophagy was mainly affected by the initiation rather than the blocking of autophagic flux. In conclusion, these results suggest that andrographolide produces antidepressant-like and anti-inflammatory effects in CUMS-induced mice which maybe mediated by the upregulation of autophagy.