Academic Journal
Salvianolic acid A promotes angiogenesis after stroke by targeting AKT to alleviate oxidative stress.
| Τίτλος: | Salvianolic acid A promotes angiogenesis after stroke by targeting AKT to alleviate oxidative stress. |
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| Συγγραφείς: | Wang L; Beijing Key Laboratory of Innovative Drug Discovery and Polymorphic Druggability Research for Cerebrovascular Diseases, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China., Zhang S; Beijing Key Laboratory of Innovative Drug Discovery and Polymorphic Druggability Research for Cerebrovascular Diseases, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China; Air Force Medical Center, PLA, Air Force Medical University, Beijing, 100142, China., Liu C; Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, 100032, China., Zhao Z; Beijing Key Laboratory of Innovative Drug Discovery and Polymorphic Druggability Research for Cerebrovascular Diseases, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China., Sun W; Beijing Key Laboratory of Innovative Drug Discovery and Polymorphic Druggability Research for Cerebrovascular Diseases, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China., Du G; Beijing Key Laboratory of Innovative Drug Discovery and Polymorphic Druggability Research for Cerebrovascular Diseases, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China., Kong L; Beijing Key Laboratory of Innovative Drug Discovery and Polymorphic Druggability Research for Cerebrovascular Diseases, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China. Electronic address: konglinglei@imm.ac.cn. |
| Πηγή: | Brain research bulletin [Brain Res Bull] 2026 Oct 15; Vol. 245, pp. 112112. Date of Electronic Publication: 2026 Sep 08. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Science Country of Publication: United States NLM ID: 7605818 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2747 (Electronic) Linking ISSN: 03619230 NLM ISO Abbreviation: Brain Res Bull Subsets: MEDLINE |
| Imprint Name(s): | Publication: New York Ny : Elsevier Science Original Publication: Phoenix, N. Y. ANKHO International Inc. |
| Ιατρικοί όροι (MeSH): | Oxidative Stress*/drug effects , Proto-Oncogene Proteins c-akt*/metabolism , Lactates*/pharmacology , Caffeic Acids*/pharmacology , Stroke*/drug therapy , Stroke*/metabolism , Angiogenesis*/drug effects , Neovascularization, Physiologic*/drug effects, Endothelial Cells/drug effects ; Endothelial Cells/metabolism ; Signal Transduction/drug effects ; Animals ; Male ; Humans ; Rats, Sprague-Dawley ; Rats ; Disease Models, Animal |
| Περίληψη: | Ischemic stroke (IS) remains a devastating cerebrovascular disease associated with high morbidity, mortality, and disability, while effective restorative therapies remain limited, highlighting an urgent unmet clinical need. Post-stroke angiogenesis contributes to vascular remodeling, restoration of cerebral blood flow, and neurovascular regeneration, making it a promising therapeutic target for IS repair. Salvianolic acid A (SAA), a phenolic acid from Salvia miltiorrhiza (Danshen), protects vascular endothelial cells and enhances neurogenesis, but its role and mechanisms in post-stroke angiogenesis remain unclear. This study investigated the effects and molecular mechanisms of SAA on post-stroke angiogenesis in vitro and in vivo. In vivo, an autologous thrombus-induced rat stroke model was established by electrocoagulation to evaluate the effects of SAA on neurological recovery and angiogenesis. In vitro, hydrogen peroxide (H₂O₂)-induced oxidative damage in human brain microvascular endothelial cells (HBMECs) was used to investigate the protective effects of SAA on endothelial function. Network pharmacology, molecular docking, and surface plasmon resonance (SPR) identified targets, with mechanistic verification both in vitro and in vivo. In the rat stroke model, SAA improved neurological deficits and enhanced functional recovery in a dose- and time-dependent manner. It also increased peri-infarct microvessel density, promoted vascular maturation, and upregulated pro-angiogenic factors (VEGF-A, Ang-1) and tight junction proteins (ZO-1, Occludin, Claudin-5). In HBMECs, SAA alleviated oxidative stress, enhanced proliferation, migration, and tube formation. Network pharmacology and SPR confirmed AKT as a core target of SAA, further activating the Nrf2 signaling pathway. AKT inhibitor MK-2206 counteracted the pro-angiogenic effect of SAA. In conclusion, SAA promotes post-stroke angiogenesis by targeting AKT and activating Nrf2-mediated antioxidant signaling, thereby protecting vascular endothelial function and improving neurological recovery. These findings provide new insights into vascular repair after IS and highlight SAA as a potential therapeutic candidate for stroke recovery via modulating angiogenesis. (Copyright © 2026. Published by Elsevier Inc.) |
| Competing Interests: | Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: AKT; Angiogenesis; Endothelial injury; Ischemic stroke; Oxidative stress; Salvianolic acid A |
| Substance Nomenclature: | 51622542XO (salvianolic acid A) EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) 0 (Lactates) 0 (Caffeic Acids) |
| Entry Date(s): | Date Created: 20260908 Date Completed: 20261006 Latest Revision: 20261006 |
| Update Code: | 20261007 |
| DOI: | 10.1016/j.brainresbull.2026.112112 |
| PMID: | 42710687 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1873-2747 |
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| DOI: | 10.1016/j.brainresbull.2026.112112 |