Ameliorative effect ofLuffa cylindricafruits onCaenorhabditis elegansand cellular models of Alzheimer's disease‐related pathology via autophagy induction

Abstract

BackgroundAlzheimer's disease (AD) is a prevalent neurodegenerative disorder without an effective cure. Natural products, while showing promise as potential therapeutics for AD, remain underexplored.AimsThis study was conducted with the goal of identifying potential anti‐AD candidates from natural sources using Caenorhabditis elegans (C. elegans) AD‐like models and exploring their mechanisms of action.Materials & MethodsOur laboratory's in‐house herbal extract library was utilized to screen for potential anti‐AD candidates using the C. elegans AD‐like model CL4176. The neuroprotective effects of the candidates were evaluated in multiple C. elegans AD‐like models, specifically targeting Aβ‐ and Tau‐induced pathology. In vitro validation was conducted using PC‐12 cells. To investigate the role of autophagy in mediating the anti‐AD effects of the candidates, RNAi bacteria and autophagy inhibitors were employed.ResultsThe ethanol extract of air‐dried fruits of Luffa cylindrica (LCE), a medicine‐food homology species, was found to inhibit Aβ‐ and Tau‐induced pathology (paralysis, ROS production, neurotoxicity, and Aβ and pTau deposition) in C. elegans AD‐like models. LCE was non‐toxic and enhanced C. elegans' health. It was shown that LCE activates autophagy and its anti‐AD efficacy is weakened with the RNAi knockdown of autophagy‐related genes. Additionally, LCE induced mTOR‐mediated autophagy, reduced the expression of AD‐associated proteins, and decreased cell death in PC‐12 cells, which was reversed by autophagy inhibitors (bafilomycin A1 and 3‐methyladenine).DiscussionLCE, identified from our natural product library, emerged as a valuable autophagy enhancer that effectively protects against neurodegeneration in multiple AD‐like models. RNAi knockdown of autophagy‐related genes and cotreatment with autophagy inhibitors weakened its anti‐AD efficacy, implying a critical role of autophagy in mediating the neuroprotective effects of LCE.ConclusionOur findings highlight the potential of LCE as a functional food or drug for targeting AD pathology and promoting human health.

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

“…For CL4176, worms were initially incubated at 16 • C for 36 h on NGM plates, with or without REF. Aβ expression and aggregation were induced by elevating the incubation temperature to 25 • C for an additional 36 h. Paralysis was evaluated as described in previous studies [36]. For CL2006, synchronized larvae at the late L4 or early adult stage were moved to NGM/FUDR plates, in the presence or absence of REF.…”

Exploring the therapeutic potential of Nelumbo nucifera leaf extract against amyloid-beta-induced toxicity in the Caenorhabditis elegans model of Alzheimer’s disease

“…Natural compounds, particularly those with medicinal and food properties, are gaining prominence as prospective preventive and therapeutic agents for neurodegenerative diseases like AD owing to their diverse components and targets, notable safety profiles, and minimal clinical side effects ( Atlante et al, 2020 ). For instance, Luffa cylindrica fruit extracts have been proven to alleviate AD-associated pathologies by stimulating autophagy in various Caenorhabditis elegans and cellular models ( Long et al, 2023a ; Iranshahy and Javadi, 2019 ). Additionally, Ligusticum chuanxiong Hort that is recognized as both a medicinal and an edible plant has exhibited potent antiaging, antioxidant, and neuroprotective properties in C. elegans ( Qin et al, 2022 ).…”