Academic Journal
SIRT3-activating, biodegradable poly-honokiol with high drug loading for thoracic aortic dissection therapy.
| Τίτλος: | SIRT3-activating, biodegradable poly-honokiol with high drug loading for thoracic aortic dissection therapy. |
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| Συγγραφείς: | Qiao X; Department of Cardiovascular Surgery, Xijing Hospital of Air Force Military Medical University, Xi'an, Shaanxi 710032, PR China., Wang D; School of Chemistry, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, PR China., Zhu H; Department of Cardiovascular Surgery, Xijing Hospital of Air Force Military Medical University, Xi'an, Shaanxi 710032, PR China., Zhang B; Department of Cardiovascular Surgery, Xijing Hospital of Air Force Military Medical University, Xi'an, Shaanxi 710032, PR China., Sun H; Department of Cardiovascular Surgery, Xijing Hospital of Air Force Military Medical University, Xi'an, Shaanxi 710032, PR China., Wang J; School of Chemistry, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, PR China., Tan G; School of Chemistry, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, PR China., Jiang L; Department of Cardiovascular Surgery, Xijing Hospital of Air Force Military Medical University, Xi'an, Shaanxi 710032, PR China., Peng X; Department of Cardiovascular Surgery, Xijing Hospital of Air Force Military Medical University, Xi'an, Shaanxi 710032, PR China., Zhang L; Department of Cardiovascular Surgery, Xijing Hospital of Air Force Military Medical University, Xi'an, Shaanxi 710032, PR China., Wang L; Department of Cardiovascular Surgery, Xijing Hospital of Air Force Military Medical University, Xi'an, Shaanxi 710032, PR China., Han S; Department of Cardiovascular Surgery, Xijing Hospital of Air Force Military Medical University, Xi'an, Shaanxi 710032, PR China., Meng L; School of Chemistry, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, PR China; Instrumental Analysis Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, PR China. Electronic address: menglingjie@mail.xjtu.edu.cn., Duan W; Department of Cardiovascular Surgery, Xijing Hospital of Air Force Military Medical University, Xi'an, Shaanxi 710032, PR China. Electronic address: duanweixun@126.com. |
| Πηγή: | Journal of advanced research [J Adv Res] 2026 Aug; Vol. 86, pp. 605-619. Date of Electronic Publication: 2025 Nov 14. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Cairo University, production and hosting by Elsevier B. V Country of Publication: Egypt NLM ID: 101546952 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2090-1224 (Electronic) Linking ISSN: 20901224 NLM ISO Abbreviation: J Adv Res Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Giza, Egypt] : Cairo University, production and hosting by Elsevier B. V. |
| Ιατρικοί όροι (MeSH): | Biphenyl Compounds*/pharmacology , Biphenyl Compounds*/chemistry , Lignans*/pharmacology , Lignans*/chemistry , Sirtuin 3*/metabolism , Aortic Dissection*/drug therapy , Aortic Dissection*/metabolism, Dissection, Thoracic Aorta/drug therapy ; Muscle, Smooth, Vascular/drug effects ; Muscle, Smooth, Vascular/metabolism ; Myocytes, Smooth Muscle/drug effects ; Myocytes, Smooth Muscle/metabolism ; Reactive Oxygen Species/metabolism ; Animals ; Phenols ; Mice ; Allyl Compounds ; Humans ; Male ; Disease Models, Animal |
| Περίληψη: | Introduction: Thoracic aortic dissection (TAD) is a life-threatening cardiovascular emergency with limited pharmacological treatment options. Objectives: Building on the strong correlation between TAD and SIRT3 observed in our preliminary studies, we aim to leverage pharmacological interventions to enhance the clinical translation of this mechanism. Methods: Based on the SIRT3 activator honokiol, we synthesized a highly efficient, pH-responsive and biodegradable poly-honokiol prodrug synthesized via a metal-free phenol-yne click polymerization strategy, achieving an unprecedented drug-loading content of 83.65%, and subsequently investigated its pharmacological activity and underlying mechanisms using a β-aminopropionitrile (BAPN)-induced TAD model. Results: Compared with honokiol, poly-honokiol markedly improved survival and reduced TAD incidence in mice by preventing vascular smooth muscle cell (VSMC) loss. Mechanistic investigations reveal that poly-honokiol activates the mitochondrial deacetylase SIRT3, which induce the deacetylation of both the antioxidant enzyme SOD2 and the key ferroptosis regulator COX2, thereby reducing ferrous ion (Fe2+) accumulation and reactive oxygen species (ROS) levels while suppressing mitochondrial permeability transition pore (mPTP) opening, ultimately attenuating ferroptosis-induced VSMC loss. Conclusion: Collectively, these findings demonstrate that poly-honokiol is a potent preventive candidate for TAD, offering both high drug-loading efficiency and targeted mitochondrial protection. (Copyright © 2025. Published by Elsevier B.V.) |
| 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: Ferroptosis; Mitochondria; Poly-honokiol; Sirtuin 3; Thoracic aortic dissection |
| Substance Nomenclature: | 0 (Biphenyl Compounds) 0 (Lignans) EC 3.5.1.- (Sirtuin 3) 11513CCO0N (honokiol) 0 (Phenols) 0 (Allyl Compounds) 0 (Sirt3 protein, mouse) 0 (Reactive Oxygen Species) |
| Entry Date(s): | Date Created: 20251116 Date Completed: 20260730 Latest Revision: 20260730 |
| Update Code: | 20260731 |
| DOI: | 10.1016/j.jare.2025.11.028 |
| PMID: | 41242496 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2090-1224 |
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| DOI: | 10.1016/j.jare.2025.11.028 |