Betula utilis extract prolongs life expectancy, protects against amyloid-β toxicity and reduces Alpha Synuclien in Caenorhabditis elegans via DAF-16 and SKN-1

Comp Biochem Physiol C Toxicol Pharmacol. 2020 Feb:228:108647. doi: 10.1016/j.cbpc.2019.108647. Epub 2019 Oct 25.

Abstract

Betula utilis (BU), an important medicinal plant that grows in high altitudes of the Himalayan region, has been utilized traditionally due to it's antibacterial, hepatoprotective, and anti-tumor properties. Here, we demonstrated the longevity and amyloid-β toxicity attenuating activity of B. utilis ethanolic extract (BUE) in Caenorhabditis elegans. Lifespan of the worms was observed under both the standard laboratory and stress (oxidative and thermal) conditions. Effect of BUE was also observed on the attenuation of age-dependent physiological parameters. Further, gene-specific mutants and green fluorescent protein (GFP)-tagged strains were used to investigate the molecular mechanism underlying the beneficial effects mediated by BUE supplementation. Our results showed that BUE (50 μg/ml) extended the mean lifespan of C. elegans by 35.99% and increased its survival under stress conditions. The BUE also reduced the levels of intracellular reactive oxygen species (ROS) by 22.47%. A delayed amyloid-β induced paralyses was observed in CL4176 transgenic worms. Interestingly, the BUE supplementation was also able to reduce the α-synuclein aggregation in NL5901 transgenic strain. Gene-specific mutant studies suggested that the BUE-mediated lifespan extension was dependent on daf-16, hsf-1, and skn-1 but not on sir-2.1 gene. Furthermore, transgenic reporter gene expression assay showed that BUE treatment enhanced the expression of stress-protective genes such as sod-3 and gst-4. Present findings suggested that ROS scavenging activity, together with multiple longevity mechanisms, were involved in BUE-mediated lifespan extension. Thus, BUE might have potential to increase the lifespan and to attenuate neuro-related disease progression.

Keywords: Anti-aging; Antioxidant; Betula utilis; Caenorhabditis elegans; Neuroprotective.

MeSH terms

  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Antioxidants / pharmacology*
  • Betula / chemistry*
  • Caenorhabditis elegans / drug effects*
  • Caenorhabditis elegans Proteins / metabolism
  • DNA-Binding Proteins / metabolism
  • Forkhead Transcription Factors / metabolism
  • Longevity*
  • Oxidative Stress / drug effects*
  • Plant Extracts / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Transcription Factors / metabolism
  • alpha-Synuclein / antagonists & inhibitors*
  • alpha-Synuclein / metabolism

Substances

  • Amyloid beta-Peptides
  • Antioxidants
  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • Forkhead Transcription Factors
  • Plant Extracts
  • Reactive Oxygen Species
  • Transcription Factors
  • alpha-Synuclein
  • daf-16 protein, C elegans
  • skn-1 protein, C elegans