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Asparagus Saponin Officinalisnin-II Alleviates Fluoride-Induced Neurotoxicity Via Activation of the SIRT1/BDNF Signaling Pathway.
| | Cheng J, Liu Y, Li Y, Yang B, Yang X, Chen X, Zhou Y, Li B, Guo L, Wang F, Tang D. |
Mitigating F toxicity Neurotoxicity Zebrafish Apoptosis Brain Oxidative Stress Animal Study Cell Study

Abstract

Original abstract online at
https://link.springer.com/article/10.1007/s12011-026-05116-3

Excessive fluoride exposure induces oxidative stress, inflammation, and neuronal damage, leading to cognitive dysfunction. This study investigated the neuroprotective mechanism of asparagus saponin Officinalisnin-II against fluoride-induced brain injury through modulation of the Silent Information Regulator 1 (SIRT1) / Brain Derived Neurotrophic Factor (BDNF) signaling pathway. Cytotoxicity and protective effects were evaluated in BV2 microglial cells treated with sodium fluoride (NaF) and various concentrations of Officinalisnin-II using cell viability, crystal violet, and EdU assays. Flow cytometry and Western blotting were employed to assess cell cycle, apoptosis, oxidative stress, and inflammatory markers. Expression of SIRT1/BDNF-related proteins was analyzed by Western blotting and immunofluorescence. The neurobehavioral effects were further examined in zebrafish using a T-maze test and quantitative real-time PCR (qRT-PCR). Officinalisnin-II markedly restored the proliferative activity of NaF-exposed BV2 cells, reduced apoptosis, and normalized cell-cycle progression. It significantly decreased intracellular reactive oxygen species and malondialdehyde levels, enhanced superoxide dismutase, glutathione peroxidase, and total antioxidant capacity, and suppressed interleukin-1 and interleukin-6 expression. The treatment upregulated SIRT1, BDNF, tropomyosin receptor kinase B (TrkB), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), while downregulating forkhead box protein O1A (FOXO1A), indicating activation of the SIRT1/BDNF pathway. In zebrafish, Officinalisnin-II improved learning and memory performance and increased expression of neuroprotective genes. These findings demonstrate that asparagus saponin Officinalisnin-II effectively mitigates fluoride-induced neurotoxicity by enhancing antioxidant capacity, reducing inflammation, and activating the SIRT1/BDNF signaling cascade, providing experimental evidence for its potential use in preventing fluorosis-related brain injury.

Data Availability

All data supporting the findings of this study are included in the article and its Supplementary Material. Further inquiries can be directed to the corresponding author upon reasonable request.

Electronic Supplementary Material

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Supplementary Material 1 (TIFF 22.8MB) (download TIFF )

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Acknowledgements

Not applicable.

Funding

This work was supported by the Natural Science Foundation of Guizhou Province (Nos. Qiankehe Cooperation Platform talents [2021] Postdoctoral Station 007, QianKeHe Support [2026]312, QianKeHe Support [2025]127); the Science and Technology Innovation Talent Team Project (Nos. GZYTD [2024] 003, GZYYFY2025002, GZSJDZX-2025-1-1,3,4,9,15); the Research Project of Education Department of Guizhou Province (No. QianJiaoJi [2023]037); and the Subject Excellent Reserve Talent Project (No. gyfyxkrc-2023-14). The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

Author information

Author notes

  1. Jinyang Cheng, Yang Liu and Yanju Li contributed equally to this work.

Authors and Affiliations

  1. Clinical Medical Research Center, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, No. 71 Bao Shan North Road, Yunyan District, Guiyang, Guizhou Province, 550001, China

    Jinyang Cheng, Yang Liu, Bo Yang, Xu Yang, Xiaoxu Chen, Ying Zhou, Bingbing Li, Lei Guo, Feiqing Wang & Dongxin Tang

  2. Department of Hematology Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, China

    Yanju Li

  3. Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin City, China

    Feiqing Wang

Contributions

JYC, FQW, YJL, and YL conceived of and designed the study; they had full access to all data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis FQW, JYC and BY wrote the report. DXT, FQW and XY critically revised the report. LG, XXC, YZ and BBL performed the statistical analysis. All authors contributed to data acquisition and analysis. All authors reviewed and approved the final version of this manuscript.

Corresponding authors

Correspondence to Feiqing Wang or Dongxin Tang.

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Competing interests

The authors declare no competing interests.