The Protective Effects of Reineckia carnea Ether Fraction against Alzheimer’s Disease Pathology: An Exploration in Caenorhabditis elegans Models

Abstract

Alzheimer’s disease (AD) presents a significant challenge to global healthcare systems, with current treatments offering only modest relief and often bringing unwanted side effects, necessitating the exploration of more effective and safer drugs. In this study, we employed the Caenorhabditis elegans (C. elegans) model, specifically the AD-like CL4176 strain expressing the human Aβ(1–42) protein, to investigate the potential of Reineckia carnea extract and its fractions. Our results showed that the Reineckia carnea ether fraction (REF) notably diminished the paralysis rates of CL4176 worms. Additionally, REF also attenuated the neurotoxicity effects prompted by Tau proteins in the BR5270 worms. Moreover, REF was observed to counteract the accumulation of Aβ and pTau proteins and their induced oxidative stress in C. elegans AD-like models. Mechanistic studies revealed that REF’s benefits were associated with the induction of autophagy in worms; however, these protective effects were nullified when autophagy-related genes were suppressed using RNAi bacteria. Together, these findings highlight Reineckia carnea ether fraction as a promising candidate for AD treatment, warranting further investigation into its autophagy-inducing components and their molecular mechanisms.

4,4′-methylenediphenol reduces Aβ-induced toxicity in a Caenorhabditis elegans model of Alzheimer’s disease

“…Under normal conditions, the body of CL4176 transgenic worms is curved (i.e., C-shaped), and the worms can move normally in culture medium. However, when the culture temperature is increased, CL4176 worms express large quantities of the Aβ 1–42 peptide, which exerts toxic effects on the muscle cells of the animals through aggregation ( Sola et al, 2015 ; Fu et al, 2023 ). To investigate the potential effect of 4,4′-methylenediphenol on the progression of Aβ toxicity-induced paralysis, we administered different concentrations (0.125, 0.25, 0.5, 1, 2, and 4 mM) of the drug to CL4176 worms and undertook a paralysis assay.…”