• The study was using C. elegans AD models to explore the mechanism of SGHWE for the first time. • SGHWE relieved Aβ-induced cytotoxicity in body wall and neurocytotoxicity. • SGHWE reduced oxidative stress levels in C. elegans . • SGHWE exerted anti-AD effects partly through the SKN-1 pathway. • SGHWE prolonged the lifespan of C. elegans . Alzheimer's disease (AD) is a complex neurodegenerative disease leading to cognitive decline and behavioral changes. With known cure often aim to alleviate symptoms, it is crucial to find novel pharmacotherapies for AD treatment. The Shenrong Guben Huanshao Wan (SGHW) originated in the mid-Qing dynasty and was refined form 65 precious Chinese herbal ingredients. It was employed in the treatment of various diseases, including nephritis, neurasthenia, and Alzheimer's disease (AD). Nevertheless, the effectiveness and the underlying mechanisms of SGHW for AD therapy were not fully elucidated. Therefore, this study aimed to investigate the anti-AD activity and mechanism of SGHW using the Caenorhabditis elegans ( C. elegans ). We preliminarily assessed the anti-AD effect of SGHWE via evaluating the paralysis rate, amyloid-β (Aβ) plaques, lifespan, and behavioral indicators of C. elegans . Subsequently, to reveal the underlying mechanism, we measured the level of reactive oxygen species (ROS), Aβ expression, and green fluorescent protein (GFP) reporter. Additionally, quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis and RNA interference assays were employed to validate the role of relevant genes. It was found that the water extract of SGHW (SGHWE) not only delayed paralysis and aging but also enhanced stress resistance of AD model worms. Besides, it alleviated serotonin hypersensitivity induced by Aβ and reduced ROS level in vivo . Notably, SGHWE showed potent potential in reducing Aβ deposition, Aβ monomers and oligomers levels and Aβ mRNA expression. Further study demonstrated that SKN-1 was involved in the anti-AD effect of SGHWE. Specifically, the expression of skn-1 and its downstream genes gst-4 were upregulated while SKN-1 nuclear translocation was promoted with SGHWE treatment. Additionally, the anti-AD effect of SGHWE was diminished by silencing skn-1 , highlighting the role of SKN-1 in AD therapy. Meanwhile, our study demonstrated the potential role of HSF-1 pathway in anti-AD effect of SGHWE. It has been demonstrated that SGHWE has the potential for AD therapy via activation of SKN-1. Our findings provide ideas and references for further research on the anti-AD effects of SGHW.
Li et al. (2026) studied this question.