Protective effect of xanthohumol against age-related brain damage

J Nutr Biochem. 2017 Nov:49:133-140. doi: 10.1016/j.jnutbio.2017.07.011. Epub 2017 Jul 27.

Abstract

It has been recently shown that xanthohumol, a flavonoid present in hops, possesses antioxidant, anti-inflammatory and chemopreventive properties. However, its role in the aging brain has not been addressed so far. Therefore, this study aimed to investigate the possible neuroprotective activity of xanthohumol against age-related inflammatory and apoptotic brain damage in male senescence-accelerated prone mice (SAMP8). Animals were divided into 4 groups: Untreated young mice, untreated old mice and old mice treated either with 1 mg kg-1 day-1 or 5 mg kg-1 day-1 xanthohumol. Young and old senescence accelerated resistant mice (SAMR1) were used as controls. After 30 days of treatment, animals were sacrificed and their brains were collected and immediately frozen in liquid nitrogen. mRNA (GFAP, TNF-α, IL-1β, AIF, BAD, BAX, XIAP, NAIP and Bcl-2) and protein (GFAP, TNF-α, IL-1β, AIF, BAD, BAX, BDNF, synaptophysin and synapsin) expressions were measured by RT-PCR and Western blotting, respectively. Significant increased levels of pro-inflammatory (TNF-α, IL-1β) and pro-apoptotic (AIF, BAD, BAX) markers were observed in both SAMP8 and SAMR1 old mice compared to young animals (P<.05) and also in SAMP8 untreated old mice compared to SAMR1 (P<.05). These alterations were significantly less evident in animals treated with both doses of xanthohumol (P<.05). Also, a reduced expression of synaptic markers was observed in old mice compared to young ones (P<.05) but it significantly recovered with 5 mg kg-1 day-1 xanthohumol treatment (P<.05). In conclusion, xanthohumol treatment modulated the inflammation and apoptosis of aged brains, exerting a protective effect on damage induced by aging.

Keywords: Aging; Apoptosis; Brain; Inflammation; Xanthohumol.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Apoptosis
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Biomarkers / metabolism
  • Brain / immunology
  • Brain / metabolism*
  • Cognitive Dysfunction / immunology
  • Cognitive Dysfunction / metabolism
  • Cognitive Dysfunction / prevention & control*
  • Dietary Supplements*
  • Encephalitis / immunology
  • Encephalitis / metabolism
  • Encephalitis / prevention & control
  • Flavonoids / administration & dosage
  • Flavonoids / therapeutic use*
  • Gene Expression Regulation, Developmental
  • Glial Fibrillary Acidic Protein / genetics
  • Glial Fibrillary Acidic Protein / metabolism
  • Inflammation Mediators / metabolism
  • Male
  • Mice, Inbred Strains
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurons / immunology
  • Neurons / metabolism*
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / therapeutic use*
  • Propiophenones / administration & dosage
  • Propiophenones / therapeutic use*
  • Synaptophysin / genetics
  • Synaptophysin / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Apoptosis Regulatory Proteins
  • Biomarkers
  • Flavonoids
  • Glial Fibrillary Acidic Protein
  • Inflammation Mediators
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Propiophenones
  • Synaptophysin
  • Syp protein, mouse
  • glial fibrillary astrocytic protein, mouse
  • xanthohumol