Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, School of Pharmaceutical Sciences, Soochow University, Suzhou, China.
Department of Clinical Pharmacy, Nanjing Brain Hospital, Nanjing Medical University, Nanjing, China.
Toxicol Appl Pharmacol. 2019 Sep 15;379:114688. doi: 10.1016/j.taap.2019.114688. Epub 2019 Jul 21.
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 antidepressant 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-1β, IL-6 as well as TNF-α were measured in the prefrontal cortex using a reagent kit, ELISA and real-time PCR. NF-κB 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-1β, IL-6 and TNF-α), NF-κB signaling (p-p65, p-IκBα) 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.
抑郁症是世界上最常见的精神障碍之一。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测轻度应激（CUMS）诱导的抑郁样行为小鼠的抗抑郁作用。强迫游泳试验、蔗糖偏好试验、悬尾试验和 Y 迷宫试验的行为学测试结果显示，穿心莲内酯给药后得到改善。采用试剂盒、ELISA 和实时 PCR 测定前额叶皮质中的促炎介质 NO 和细胞因子 IL-1β、IL-6 和 TNF-α。采用 Western blot 检测前额叶皮质中的 NF-κB 信号转导、NLRP3 炎症小体组装和自噬过程。结果发现，5mg/kg 穿心莲内酯治疗明显改善了抑郁样行为。此外，5mg/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、COX-2、iNOS、IL-1β、IL-6 和 TNF-α）、NF-κB 信号转导（p-p65、p-IκBα）和 NLRP3 炎症小体组装（NLRP3、ASC 和 caspase-1）的表达。此外，穿心莲内酯治疗后自噬水平增加。最后，氯喹（CQ）的应用削弱了穿心莲内酯的抗抑郁和抗炎作用，这表明穿心莲内酯诱导的自噬主要受自噬起始而不是自噬流阻断的影响。综上所述，这些结果表明，穿心莲内酯在 CUMS 诱导的小鼠中产生抗抑郁和抗炎作用，可能是通过上调自噬介导的。
