Alpha-Asarone Ameliorates Dry Age-Related Macular Degeneration by Modulating the P2X7/NLRP3 Inflammasome Axis.
- 1Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China.
- 2Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Abstract
Purpose
To examine whether α-asarone (ASA) protects dry age-related macular degeneration (dAMD) from sodium iodate (SI) injury by modulating the P2X7-mediated NLRP3 inflammasome axis.Methods
Male Sprague-Dawley rats were treated with SI to establish a dAMD model. Retinal structure and function were evaluated using electroretinography (ERG), optical coherence tomography (OCT), and hematoxylin-eosin staining, whereas the expression of functional and inflammatory proteins was analyzed via immunofluorescence and Western blotting. Molecular docking, molecular dynamics (MD) simulations, and cellular thermal shift assays (CETSA) were performed to explore the potential interaction between ASA and P2X7. In vitro, SI-stimulated ARPE-19 cells were used to evaluate the protective effects of ASA and the involvement of P2X7 through Cell Counting Kit-8 assays, Annexin V-FITC/PI staining, Fluo-4 staining, YO-PRO-1 uptake detection, ELISA, and Western blotting.Results
ASA preserved retinal structure and function, maintained the expression of key functional proteins, suppressed microglial activation, and attenuated inflammatory responses. Computational modeling suggested a stable potential interaction between ASA and P2X7, and CETSA further supported ASA-induced modulation of P2X7 thermal stability in cells. In vitro, ASA enhanced cell viability, reduced apoptosis, attenuated Ca²⁺ influx and P2X7 macropore formation, decreased the release of inflammatory cytokines, and downregulated P2X7/NLRP3 pathway, all of which were effectively abolished by activating P2X7.Conclusions
The findings demonstrate that ASA mitigates SI-induced dAMD injury by suppressing the P2X7/NLRP3 inflammatory pathway. This study identifies a promising new therapeutic strategy for dAMD.
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BibTeX
@article{wang2026alphaasarone,
title = {{Alpha-Asarone Ameliorates Dry Age-Related Macular Degeneration by Modulating the P2X7/NLRP3 Inflammasome Axis.}},
author = {Xin Wang and Yuxiu Bi and Yuxiang Liu and Yao Nie and Junzhou Ding and Lei Yu and Shengjun Mao},
journal = {Investigative ophthalmology \& visual science},
year = {2026},
month = oct,
doi = {10.1167/iovs.67.12.30},
url = {https://europepmc.org/article/MED/42878578},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Alpha-Asarone Ameliorates Dry Age-Related Macular Degeneration by Modulating the P2X7/NLRP3 Inflammasome Axis.
AU - Xin Wang
AU - Yuxiu Bi
AU - Yuxiang Liu
AU - Yao Nie
AU - Junzhou Ding
AU - Lei Yu
AU - Shengjun Mao
PY - 2026
DA - 2026/10/01
JO - Investigative ophthalmology & visual science
DO - 10.1167/iovs.67.12.30
UR - https://europepmc.org/article/MED/42878578
AB - Purpose To examine whether α-asarone (ASA) protects dry age-related macular degeneration (dAMD) from sodium iodate (SI) injury by modulating the P2X7-mediated NLRP3 inflammasome axis.Methods Male Sprague-Dawley rats were treated with SI to establish a dAMD model. Retinal structure and function were evaluated using electroretinography (ERG), optical coherence tomography (OCT), and hematoxylin-eosin staining, whereas the expression of functional and inflammatory proteins was analyzed via immunofluorescence and Western blotting. Molecular docking, molecular dynamics (MD) simulations, and cellular thermal shift assays (CETSA) were performed to explore the potential interaction between ASA and P2X7. In vitro, SI-stimulated ARPE-19 cells were used to evaluate the protective effects of ASA and the involvement of P2X7 through Cell Counting Kit-8 assays, Annexin V-FITC/PI staining, Fluo-4 staining, YO-PRO-1 uptake detection, ELISA, and Western blotting.Results ASA preserved retinal structure and function, maintained the expression of key functional proteins, suppressed microglial activation, and attenuated inflammatory responses. Computational modeling suggested a stable potential interaction between ASA and P2X7, and CETSA further supported ASA-induced modulation of P2X7 thermal stability in cells. In vitro, ASA enhanced cell viability, reduced apoptosis, attenuated Ca²⁺ influx and P2X7 macropore formation, decreased the release of inflammatory cytokines, and downregulated P2X7/NLRP3 pathway, all of which were effectively abolished by activating P2X7.Conclusions The findings demonstrate that ASA mitigates SI-induced dAMD injury by suppressing the P2X7/NLRP3 inflammatory pathway. This study identifies a promising new therapeutic strategy for dAMD.
SN - 0146-0404
SN - 1552-5783
ER -