Humulus japonicus rescues autistic‑like behaviours in the BTBR T+ Itpr3tf/J mouse model of autism

Mol Med Rep. 2021 Jun;23(6):448. doi: 10.3892/mmr.2021.12087. Epub 2021 Apr 21.

Abstract

Humulus japonicus (HJ) is a traditional herbal medicine that exhibits anti‑inflammatory, antimicrobial and anti‑tumor effects that is used for the treatment of hypertension, pulmonary disease and leprosy. Recently, it has also been reported that HJ demonstrates neuroprotective properties in animal models of neurodegenerative diseases. The current study hypothesised that the administration of HJ would exhibit therapeutic effects in autism spectrum disorder (ASD), a neurodevelopmental disorder with lifelong consequences. The BTBR T+ Itpr3tf/J mouse model of ASD was used to investigate the anti‑autistic like behavioural effects of HJ. Chronic oral administration of the ethanolic extract of HJ significantly increased social interaction, attenuated repetitive grooming behaviour and improved novel‑object recognition in BTBR mice. Anti‑inflammatory effects of HJ in the brain were analysed using immunohistochemistry and reverse‑transcription quantitative PCR analysis. Microglia activation was markedly decreased in the striatum and hippocampus, and pro‑inflammatory cytokines, including C‑C Motif Chemokine Ligand 2, interleukin (IL)‑1β and IL‑6, were significantly reduced in the hippocampus following HJ treatment. Moreover, HJ treatment normalised the phosphorylation levels of: N‑methyl‑D‑aspartate receptor subtype 2B and calcium/calmodulin‑dependent protein kinase type II subunit α in the hippocampus of BTBR mice. The results of the present study demonstrated that the administration of HJ may have beneficial potential for ameliorating behavioural deficits and neuroinflammation in ASD.

Keywords: Humulus japonicus; Autism spectrum disorder; therapeutic effect; animal model.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Autism Spectrum Disorder / drug therapy
  • Autistic Disorder / drug therapy*
  • Autistic Disorder / genetics
  • Behavior, Animal / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Hippocampus / pathology
  • Humulus / chemistry*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Phosphorylation / drug effects
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use*

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Plant Extracts

Grants and funding

This study was supported by the KRIBB Research Initiative Program of the Republic of Korea and by the Development of Platform Technology for Innovative Medical Measurements Program (grant no. KRISS-2020-GP2020-0004) from the Korea Research Institute of Standards and Science.