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ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Ethnopharmacology

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1658991

Selaginella Extracts Extend Lifespan and Mitigate Oxidative Stress in Caenorhabditis elegans

Provisionally accepted
Xueqing  ChenXueqing Chen1Bing  Jian YanBing Jian Yan2Yingmei  WuYingmei Wu2Wenjing  QuanWenjing Quan2Yu  LiuYu Liu2Yaning  HuangYaning Huang2yinjie  Shaoyinjie Shao2Yuan  WangYuan Wang1Qi  ZhouQi Zhou1Yifei  LiuYifei Liu2Songlin  LiuSonglin Liu2Jing  WangJing Wang3Pan  LiPan Li4Zhaohua  ShiZhaohua Shi2*Peng  ShuPeng Shu1*Junbo  GouJunbo Gou2*
  • 1Shenzhen Hujia Technology Co Ltd, Shenzhen, China
  • 2Hubei University of Chinese Medicine, Wuhan, China
  • 3Western Herbs (Hubei) Biotechnology Co., Ltd., Wuhan 430070, China, Wuhan, China
  • 4South China Agricultural University, Guangzhou, China

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

Selaginella species have been traditionally used in medicine and cosmetics, yet their potential lifespan-extending properties remain underexplored. In this study, two representative Selaginella extracts—S4 (high in amentoflavone) and S16 (low in amentoflavone)—were selected for evaluation in Caenorhabditis elegans. Both extracts extended lifespan under normal conditions and modulated conserved longevity pathways, such as MAPK and FOXO signaling, with daf-16 and egl-8 identified as key hub genes. Amentoflavone was further validated as a critical bioactive component, extending lifespan by 63.81% and enhancing stress resistance. It promoted DAF-16 nuclear translocation and upregulation of antioxidant genes (e.g., sod-3, gst-3/4, hsp-16.48/12.6), thereby reducing ROS levels. These results demonstrate that Selaginella extract and amentoflavone delay aging primarily via DAF-16/FOXO-mediated antioxidant mechanisms, highlighting their potential as natural lifespan-extending agents.

Keywords: Amentoflavone, Caenorhabditis elegans, DAF-16/FOXO pathway, Lifespan, Selaginella tamariscina, Transcriptome

Received: 03 Jul 2025; Accepted: 29 Sep 2025.

Copyright: © 2025 Chen, Jian Yan, Wu, Quan, Liu, Huang, Shao, Wang, Zhou, Liu, Liu, Wang, Li, Shi, Shu and Gou. 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:
Zhaohua Shi, zhshi78@hbucm.edu.cn
Peng Shu, shupeng@hbn.cn
Junbo Gou, junbogou@163.com

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