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Andrographolide triggers autophagy-mediated inflammation inhibition and attenuates chronic unpredictable mild stress (CUMS)-induced depressive-like behavior in mice.

Abstract：

: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.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Geng J,Liu J,Yuan X,Liu W,Guo W

doi

10.1016/j.taap.2019.114688

subject

Has Abstract

pub_date

2019-09-15 00:00:00

pages

114688

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(19)30296-0

journal_volume

379

pub_type

杂志文章

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Andrographolide triggers autophagy-mediated inflammation inhibition and attenuates chronic unpredictable mild stress (CUMS)-induced depressive-like behavior in mice.