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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Ethnopharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1408031

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

Provisionally accepted
Yongping Wen Yongping Wen 1Hai-Jun Fu Hai-Jun Fu 2Qin Chen Qin Chen 3Cai Lan Cai Lan 2Qin D. Lian Qin D. Lian 2Jianming Wu Jianming Wu 2An G. Wu An G. Wu 2Xiao-Gang Zhou Xiao-Gang Zhou 4*
  • 1 Chengdu University, Chengdu, Sichuan Province, China
  • 2 Southwest Medical University, Luzhou, Sichuan, China
  • 3 Nanchong Food and Drug Inspection Institute, Nanchong, China
  • 4 Drug Discovery Research Center, Southwest Medical University, Luzhou, China

The final, formatted version of the article will be published soon.

    Alzheimer's disease (AD) presents a global health crisis with limited therapeutic options, urging the exploration of alternative strategies. A pivotal pathology in AD involves amyloid beta (Aβ) aggregation, and addressing Aβ aggregation alongside oxidative stress is vital for effective intervention. Natural compounds from medicinal and food sources have emerged as potential preventive and therapeutic agents, among which Nelumbo nucifera leaf extract (NLE) shows promising properties. In this study, we investigated NLE's potential in countering AD and elucidated the underlying mechanisms using transgenic Caenorhabditis elegans (C. elegans) models. The results revealed that NLE significantly reduced paralysis rates in CL4176 and CL2006 worms while enhancing food-searching capabilities in CL2355 worms. Furthermore, NLE attenuated Aβ aggregate accumulation and mitigated Aβ-induced oxidative stress in C.elegans. Moreover, NLE extended lifespan of worms under oxidative and thermal stress conditions, concurrently elevating the expression of stress-resistance-related proteins (SOD-3, GST-4, HSP-4, and HSP-6). Additionally, NLE induced autophagy in C. elegans, as evidenced by reduced p62 levels in BC12921 worms and the formation ofLGG-1 + structures in DA2123 worms. However, RNAi-mediated inhibition of autophagy-related genes, including bec-1 and vps-34, negated the protective effects of NLE against Aβ-induced paralysis and aggregate accumulation, suggesting that NLE ameliorates Aβ-induced toxicity by activating autophagy in C. elegans. Together, these findings underscore NLE as a promising candidate for further investigation in AD management, offering multifaceted approaches to mitigate AD-related pathology and stress-related challenges.

    Keywords: Alzheimer's disease, Aβ, Nelumbo nucifera leaf extract, C. elegans, Autophagy

    Received: 28 Mar 2024; Accepted: 16 May 2024.

    Copyright: © 2024 Wen, Fu, Chen, Lan, Lian, Wu, Wu and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Xiao-Gang Zhou, Drug Discovery Research Center, Southwest Medical University, Luzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.