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Volume 27
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10.3390/ijms27114749
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Astilbin Protects Against Ischemic Stroke by Regulating ERK1/2/CREB/p90RSK Signaling and Ferroptosis-Related SLC7A11/ACSL4/GPX4 Axis: Insights from Network Pharmacology, Multi-Omics, and Molecular Dynamics

by
Chang Jin
1,
Yue Zhang
1,
Bing Li
1,
Zhifeng Cheng
1,
Meizhu Zheng
2,*,
Weihua Dong
3,*,
Kai Song
1 and
Yongxing Ai
4
1
College of Life Science, Changchun Normal University, Changchun 130032, China
2
The Central Laboratory, Changchun Normal University, Changchun 130032, China
3
School of Geographical Sciences, Changchun Normal University, Changchun 130032, China
4
College of Animal Science, Jilin University, Changchun 130062, China
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2026, 27(11), 4749; https://doi.org/10.3390/ijms27114749
Submission received: 13 April 2026 / Revised: 16 May 2026 / Accepted: 21 May 2026 / Published: 25 May 2026
(This article belongs to the Section Molecular Pharmacology)
Versions Notes

Abstract

Ischemic stroke is an acute cerebrovascular disease with high disability and morbidity. However, therapeutic approaches are restricted by a narrow time window for reperfusion. Astilbin has various pharmacological activities and good therapeutic potential against ischemic stroke and neurodegenerative diseases. Nevertheless, Astilbin’s mechanism of action remains unclear. Here, we used an integrated strategy that includes network pharmacology, omics validation, and functional verification. Potential targets of Astilbin were predicted using SwissTargetPrediction and PharmMapper, and cross-analyzed with IS-related genes from multiple databases. GO/KEGG enrichment analyses showed that Astilbin synergistically regulates stroke-associated pathways (e.g., MAPK, AGE-RAGE). Combined transcriptomic and metabolomic assays confirmed that Astilbin ameliorates OGD/R-induced oxidative stress and metabolic disorders by modulating the MAPK and ferroptosis pathways. Molecular docking and dynamics simulations revealed that Astilbin has high affinity for core targets (ERK1/2, CREB, p90RSK, MMP9) and binds stably to MMP9. Using an OGD/R-injured neuronal-like PC12 cell line, in vitro assays confirmed that Astilbin alleviates oxidative stress, calcium overload, lipid peroxidation, and intracellular iron levels, while also modulating apoptosis- and inflammation-related genes. Overall, this study has established a comprehensive pharmacological framework for the use of Astilbin against IS, clarified its multi-target, multi-pathway neuroprotective mechanisms of action, and provided evidence for its potential in the treatment of IS.
Keywords: ischemic stroke; Astilbin; network pharmacology; multi-omics; mechanism of action ischemic stroke; Astilbin; network pharmacology; multi-omics; mechanism of action

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MDPI and ACS Style

Jin, C.; Zhang, Y.; Li, B.; Cheng, Z.; Zheng, M.; Dong, W.; Song, K.; Ai, Y. Astilbin Protects Against Ischemic Stroke by Regulating ERK1/2/CREB/p90RSK Signaling and Ferroptosis-Related SLC7A11/ACSL4/GPX4 Axis: Insights from Network Pharmacology, Multi-Omics, and Molecular Dynamics. Int. J. Mol. Sci. 2026, 27, 4749. https://doi.org/10.3390/ijms27114749

AMA Style

Jin C, Zhang Y, Li B, Cheng Z, Zheng M, Dong W, Song K, Ai Y. Astilbin Protects Against Ischemic Stroke by Regulating ERK1/2/CREB/p90RSK Signaling and Ferroptosis-Related SLC7A11/ACSL4/GPX4 Axis: Insights from Network Pharmacology, Multi-Omics, and Molecular Dynamics. International Journal of Molecular Sciences. 2026; 27(11):4749. https://doi.org/10.3390/ijms27114749

Chicago/Turabian Style

Jin, Chang, Yue Zhang, Bing Li, Zhifeng Cheng, Meizhu Zheng, Weihua Dong, Kai Song, and Yongxing Ai. 2026. "Astilbin Protects Against Ischemic Stroke by Regulating ERK1/2/CREB/p90RSK Signaling and Ferroptosis-Related SLC7A11/ACSL4/GPX4 Axis: Insights from Network Pharmacology, Multi-Omics, and Molecular Dynamics" International Journal of Molecular Sciences 27, no. 11: 4749. https://doi.org/10.3390/ijms27114749

APA Style

Jin, C., Zhang, Y., Li, B., Cheng, Z., Zheng, M., Dong, W., Song, K., & Ai, Y. (2026). Astilbin Protects Against Ischemic Stroke by Regulating ERK1/2/CREB/p90RSK Signaling and Ferroptosis-Related SLC7A11/ACSL4/GPX4 Axis: Insights from Network Pharmacology, Multi-Omics, and Molecular Dynamics. International Journal of Molecular Sciences, 27(11), 4749. https://doi.org/10.3390/ijms27114749

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