Academic Journal
Sodium danshensu mitigates myocardial ischemia-reperfusion injury by attenuating ferroptosis through Nrf2/SLC7A11/GPX4 pathway.
| Title: | Sodium danshensu mitigates myocardial ischemia-reperfusion injury by attenuating ferroptosis through Nrf2/SLC7A11/GPX4 pathway. |
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| Authors: | Liu P; School of Medicine Shanghai University, Shanghai 200444, China., Luo Y; School of Medicine Shanghai University, Shanghai 200444, China., Zhang Y; College of Pharmacology, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China., Dong Y; Department of Pharmacy, Shanghai Pudong New Area People's Hospital, Shanghai 201200, PR China., Qiu Z; Shenzhen Medicines and Health Products Imp, & Exf, Co, Ltd, Shenzhen 518001, China. Electronic address: boazhk@126.com., Chen T; School of Medicine Shanghai University, Shanghai 200444, China. Electronic address: cttc1990@126.com., Zhang C; School of Medicine Shanghai University, Shanghai 200444, China. Electronic address: zc843016@shu.edu.cn. |
| Source: | Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2026 Aug; Vol. 513, pp. 117863. Date of Electronic Publication: 2026 May 12. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Academic Press Country of Publication: United States NLM ID: 0416575 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0333 (Electronic) Linking ISSN: 0041008X NLM ISO Abbreviation: Toxicol Appl Pharmacol Subsets: MEDLINE |
| Imprint Name(s): | Publication: New York, NY : Academic Press Original Publication: New York. |
| MeSH Terms: | Ferroptosis*/drug effects , NF-E2-Related Factor 2*/metabolism , Myocardial Reperfusion Injury*/drug therapy , Myocardial Reperfusion Injury*/prevention & control , Myocardial Reperfusion Injury*/pathology , Myocardial Reperfusion Injury*/metabolism , Phospholipid Hydroperoxide Glutathione Peroxidase*/metabolism , Lactates*/pharmacology, Signal Transduction/drug effects ; Oxidative Stress/drug effects ; Myocytes, Cardiac/drug effects ; Myocytes, Cardiac/pathology ; Animals ; Male ; Mice ; Mice, Inbred C57BL |
| Abstract: | Myocardial ischemia-reperfusion injury (MI/RI) frequently occurs in individuals experiencing acute myocardial infarction (AMI) after undergoing reperfusion therapy. The process of ferroptosis is intricately linked to MI/RI, and the nuclear factor erythroid 2-related factor 2 (Nrf2) is crucial in either promoting or impeding ferroptosis. Sodium danshensu (SDSS), a water-soluble substance obtained from the Traditional Chinese Medicine known as Danshen, exhibits significant impacts on oxidative stress and inflammation. However, the specific molecular mechanisms by which it addresses MI/RI are not fully understood. This study aims to investigate the therapeutic effects and underlying mechanisms of SDSS in mitigating MI/RI. Using both in vivo and in vitro models, we evaluated the impact of SDSS on ferroptosis and its associated regulators. Myocardial injury was assessed via echocardiography, Masson's trichrome, and H&E staining. Mitochondrial function was examined through transmission electron microscopy and JC-1 staining. Expression levels of ferroptosis-related markers, including Nrf2, GPX4, and SLC7A11, were measured using Western blotting, immunohistochemistry, and immunofluorescence. The findings indicated that SDSS provided significant cardiac protection and reduced MI/RI by inhibiting ferroptosis through modulation of the Nrf2 pathway, which in turn diminished oxidative stress and restored mitochondrial function in both in vivo and in vitro settings. Mechanistically, SDSS not only enhanced the levels of Nrf2 but also promoted its translocation into the nucleus, which in turn initiated the subsequent antioxidant defense processes. In summary, this research highlights that SDSS alleviates MI/RI by targeting the Nrf2/SLC7A11/GPX4 signaling pathway, indicating its potential as a therapeutic agent for ferroptosis inhibition. (Copyright © 2024. Published by Elsevier Inc.) |
| Competing Interests: | Declaration of competing interest The authors affirm that there are no competing financial interests or personal relationships pertinent to this work that are undisclosed. |
| Contributed Indexing: | Keywords: Ferroptosis; Myocardial ischemia-reperfusion; Nrf2; Sodium danshensu |
| Substance Nomenclature: | 0 (NF-E2-Related Factor 2) 4GF33A5PAJ (3,4-dihydroxyphenyllactic acid) 0 (Nfe2l2 protein, mouse) EC 1.11.1.12 (Phospholipid Hydroperoxide Glutathione Peroxidase) 0 (Lactates) EC 1.11.1.9 (glutathione peroxidase 4, mouse) |
| Entry Date(s): | Date Created: 20260512 Date Completed: 20260612 Latest Revision: 20260612 |
| Update Code: | 20260613 |
| DOI: | 10.1016/j.taap.2026.117863 |
| PMID: | 42119709 |
| Database: | MEDLINE |
| ISSN: | 1096-0333 |
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| DOI: | 10.1016/j.taap.2026.117863 |