Deer antler extracts reduce amyloid-beta toxicity in a Caenorhabditis elegans model of Alzheimer's disease

Abstract

Ethnopharmacological relevance: Velvet antler extracts (VAE) are composed of a variety of active substances and growth factors, and have been reported to improve sleep quality and memory.

Aim of the study: We aimed to explore the protective effects and mechanism of action for VAE on Alzheimer's disease (AD) using a transgenic Caenorhabditis elegans model.

Materials and methods: C. elegans were cultivated at 40% relative humidity on solid nematode growth medium (NGM) containing live E. coli (OP50) as the food source, with Strain N2 (normal) held at 20 °C and the CL4176s (transgenic) held at 16 °C. AD-like aggregation of Aβ peptide in the CL4176s strain is induced by lifting the temperature to 25 °C. Nematodes were treated with three types of VAEs and Resveratrol (positive control). Analyses included qRT-PCR for quantification of gene transcripts of interest; ELISA for measuring levels of amyloid-β protein; Thioflavin T fluorescent staining for localizing Aβ depositions; assays for reactive oxygen species (ROS) and superoxide dismutase activity (SOD).

Results: VAEs reduced β-amyloid peptide (Aβ) toxicity in the transgenic C. elegans model. An enzymatically-digested VAE (EDVAE) was superior to both a cold-water VAE (CWVAE) and a hot-water VAE (HWVAE) from the same velvet antler. EDVAE treatment reduced the severity of the Aβ-induced paralysis phenotype and decreased the amount of Aβ deposits in the AD model nematodes, and these effects were found to be significantly better than that of the positive control Resveratrol. In addition, EDVAE treatment reduced production of ROS (induced by Aβ), enhanced SOD activity, and elevated expression levels of antioxidant-related transcription factors, although it is not known whether these effects were achieved directly or indirectly.

Conclusion: EDVAE had a protective role in Aβ-induced toxicity in the transgenic AD nematodes, possibly through reducing accumulation of toxic Aβ and enhancing the ability of nematodes to resist oxidative stress. Thus, EDVAE has potential to be an effective treatment to relieve the symptoms of AD.

Keywords: Alzheimer's disease; Amyloid-beta; C. elegans; Oxidative stress; Velvet antler extract.