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Allicin attenuated chronic social defeat stress induced depressive-like behaviors through suppression of NLRP3 inflammasome

  • Wenqi Gao
  • Wei Wang
  • Gang Liu
  • Jing Zhang
  • Jian Yang
  • Zhifang Deng
Original Article

Abstract

Allicin, one of the main biologically active compounds derived from garlic, was previously reported to possess multiple pharmacological activities. Whether allicin protected against chronic social defeat stress (CSDS) induced depressive-like behaviors remained unknown. Thus, our present study for the first time investigated the potential antidepressant effects and the mechanisms of allicin on the CSDS mice model. Thirty minutes before social defeat stress, allicin (2, 10, 50 mg/kg) was treated by intraperitoneal injection. The duration times of CSDS model establishment and allicin intervene were 10 days. Subsequently, the force swimming test (FST), social interaction test (SIT), and sucrose preference test (SPT) were applied for behavioral assessments. The levels of inflammation mediators were determined by commercial ELISA kits. The concentration of iron was tested, and relative protein expressions were measured by western blot. Oxidative stress and apoptosis markers were also detected by commercial kits and western blot. The behavioral defects induced by social defeat stress were obviously improved by allicin. Microglia activation, as well as inflammatory cytokines elevation in the hippocampus of CSDS also down-regulated by administration of allicin. Furthermore, content of iron and protein expressions of key components in iron metabolism were remarkably aberrant changed in the CSDS mice hippocampus, meanwhile, allicin ameliorated this phenomenon. Allicin decreased the production of reactive oxygen species (ROS), malondialdehyde (MDA), and protein carbonyl, and the protein expression of NOX4, as well as up-regulated the activities of superoxide dismutase (SOD) and Nrf2/HO-1 pathway. In addition, allicin attenuated the enhanced neuronal apoptosis. Finally, allicin supplementation inhibited the Nucleotide-binding oligomerization domain containing 3 (NLRP3) inflammasome hyperactivity, and the expressions of inflammasome components, such as ACS, caspase-1, and IL-1β in the hippocampus of CSDS mice. Allicin attenuated depressive-like behaviors of CSDS mice through reducing neuroinflammation, ameliorating iron abnromal accumulation, balacing oxidative stress, and attenuation neuronal apoptosis in the hippocampus via suppression of NLRP3 inflammasome.

Keywords

Allicin Chronic social defeat stress Depressive-like behavior Neuroinflammation Iron homeostasis NLRP3 

Abbreviations

CSDS

Chronic social defeat stress

SPT

Sucrose preference test

SIT

Social interaction test

FST

Force swimming test

Fpn1

Ferroportin

DMT-1

Divalent metal trasporter-1

Iba-1

Ionized calcium-binding adapter molecular 1

ROS

Reactive oxygen species

MDA

Malondialdehyde

SOD

Superoxide dismutase

NOX

NADPH oxidase

Nrf2

Nuclear factor erythroid 2-related factor 2

HO-1

Heme oxygenase-1

NLRP3

Nucleotide-binding oligomerization domain containing 3

IL-1β

Interleukin-1β

Notes

Acknowledgements

We gratefully acknowledge the National Natural Science Foundation of China (81470387) for the generous financial support.

Compliance with ethical standards

Competing interests

The authors declare that they have no competing interests.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Central Experimental Laboratory & Yichang Key Laboratory of Ischemic Cardiovascular and Cerebrovascular Disease Translational Medicine, The First College of Clinical Medical ScienceChina Three Gorges University & Yichang Central People’s HospitalYichangChina
  2. 2.Department of Pharmacology, School of Basic Medical SciencesGuizhou Medical UniversityGuiyangChina
  3. 3.Department of Pharmacy, The First College of Clinical Medical ScienceChina Three Gorges University & Yichang Central People’s HospitalYichangChina

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