Abstract
Background
The primary pathogenic factors of Alzheimer’s disease (AD) have been identified as oxidative stress, inflammatory damage, and apoptosis. Chrysophanol (CHR) has a good neuroprotective effect on AD, however, the potential mechanism of CHR remains unclear.
Purpose
In this study, we focused on the ROS/TXNIP/NLRP3 pathway to determine whether CHR regulates oxidative stress and neuroinflammation.
Methods
d-galactose and Aβ25-35 combination were used to build an in vivo model of AD, and the Y-maze test was used to evaluate the learning and memory function of rats. Morphological changes of neurons in the rat hippocampus were observed using hematoxylin and eosin (HE) staining. AD cell model was established by Aβ25-35 in PC12 cells. The DCFH-DA test identified reactive oxygen species (ROS). The apoptosis rate was determined using Hoechst33258 and flow cytometry. In addition, the levels of MDA, LDH, T-SOD, CAT, and GSH in serum, cell, and cell culture supernatant were detected by colorimetric method. The protein and mRNA expressions of the targets were detected by Western blot and RT-PCR. Finally, molecular docking was used to further verify the in vivo and in vitro experimental results.
Results
CHR could significantly improve learning and memory impairment, reduce hippocampal neuron damage, and reduce ROS production and apoptosis in AD rats. CHR could improve the survival rate, and reduce the oxidative stress and apoptosis in the AD cell model. Moreover, CHR significantly decreased the levels of MDA and LDH, and increased the activities of T-SOD, CAT, and GSH in the AD model. Mechanically, CHR significantly reduced the protein and mRNA expression of TXNIP, NLRP3, Caspase-1, IL-1β, and IL-18, and increase TRX.
Conclusions
CHR exerts neuroprotective effects on the Aβ25-35-induced AD model mainly by reducing oxidative stress and neuroinflammation, and the mechanism may be related to ROS/TXNIP/NLRP3 signaling pathway.
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Data availability
The data used to support the findings of this study are available from the corresponding author upon request.
Change history
18 January 2024
A Correction to this paper has been published: https://doi.org/10.1007/s10787-023-01411-w
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Acknowledgements
This study was supported by the Key Project of Overseas Visits for the Excellent Young Talents in Universities of Anhui Province in China (gxgwfx2020041); National Natural Science Foundation of China (81873351); Academic funding program for top talents in universities of Anhui Province (gxbjZD2022024).
Funding
The funding was provided by Key Project of Overseas Visits for the Excellent Young Talents in Universities of Anhui Province in China, gxgwfx2020041, Peng Zhou, National Natural Science Foundation of China, 81873351, Biao Cai, Academic funding program for top talents in universities of Anhui Province, gxbjZD2022024.
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MZ: Formal analysis, Validation, Writing-original draft. Z-xD: Formal analysis, Validation, Writing-original draft. WH: Formal analysis, Validation. JL: Formal analysis, Validation. SY: Formal analysis, Validation, Investigation. S-lH: Formal analysis, Validation, Investigation. PZ: Conceptualization, Methodology, Supervision, Visualization, Writing-review & editing. BC: Conceptualization, Methodology, Supervision, Visualization, Writing-review & editing. All data were generated in-house, and no paper mill was used. All authors agree to be accountable for all aspects of work ensuring integrity and accuracy.
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Zhang, M., Ding, Zx., Huang, W. et al. Chrysophanol exerts a protective effect against Aβ25-35-induced Alzheimer’s disease model through regulating the ROS/TXNIP/NLRP3 pathway. Inflammopharmacol 31, 1511–1527 (2023). https://doi.org/10.1007/s10787-023-01201-4
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DOI: https://doi.org/10.1007/s10787-023-01201-4