AUTHOR=Wen Yong-Ping , Fu Hai-Jun , Chen Qin , Lan Cai , Qin Da-Lian , Wu Jian-Ming , Wu An-Guo , Zhou Xiao-Gang 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1408031

DOI=10.3389/fphar.2024.1408031

ISSN=1663-9812

ABSTRACT=<p><bold>Introduction:</bold> Alzheimer’s disease (AD) represents a critical global health challenge with limited therapeutic options, prompting the exploration of alternative strategies. A key pathology in AD involves amyloid beta (Aβ) aggregation, and targeting both Aβ aggregation and oxidative stress is crucial for effective intervention. Natural compounds from medicinal and food sources have emerged as potential preventive and therapeutic agents, with <italic>Nelumbo nucifera</italic> leaf extract (NLE) showing promising properties.</p><p><bold>Methods:</bold> In this study, we utilized transgenic <italic>Caenorhabditis elegans</italic> (<italic>C. elegans</italic>) models to investigate the potential of NLE in countering AD and to elucidate the underlying mechanisms. Various assays were employed to assess paralysis rates, food-searching capabilities, Aβ aggregate accumulation, oxidative stress, lifespan under stress conditions, and the expression of stress-resistance-related proteins. Additionally, autophagy induction was evaluated by measuring P62 levels and the formation of LGG-1<sup>+</sup> structures, with RNAi-mediated inhibition of autophagy-related genes to confirm the mechanisms involved.</p><p><bold>Results:</bold> The results demonstrated that NLE significantly reduced paralysis rates in CL4176 and CL2006 worms while enhancing food-searching capabilities in CL2355 worms. NLE also attenuated Aβ aggregate accumulation and mitigated Aβ-induced oxidative stress in <italic>C. elegans</italic>. Furthermore, NLE extended the lifespan of worms under oxidative and thermal stress conditions, while concurrently increasing the expression of stress-resistance-related proteins, including SOD-3, GST-4, HSP-4, and HSP-6. Moreover, NLE induced autophagy in <italic>C. elegans</italic>, as evidenced by reduced P62 levels in BC12921 worms and the formation of LGG-1<sup>+</sup> structures in DA2123 worms. The RNAi-mediated inhibition of autophagy-related genes, such as <italic>bec-1</italic> and <italic>vps-34</italic>, negated the protective effects of NLE against Aβ-induced paralysis and aggregate accumulation.</p><p><bold>Discussion:</bold> These findings suggest that NLE ameliorates Aβ-induced toxicity by activating autophagy in <italic>C. elegans</italic>. The study underscores the potential of NLE as a promising candidate for further investigation in AD management, offering multifaceted approaches to mitigate AD-related pathology and stress-related challenges.</p>