Academic Journal
Honokiol protects against acute pancreatitis by activating SIRT3 to restore mitochondrial oxidative phosphorylation and alleviate hyperacetylation.
| Τίτλος: | Honokiol protects against acute pancreatitis by activating SIRT3 to restore mitochondrial oxidative phosphorylation and alleviate hyperacetylation. |
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| Συγγραφείς: | Miao YF; Department of Emergency Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China., Yao JQ; Department of Integrated Traditional Chinese and Western Medicine, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China., Peng Y; School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan Province, China., Bai D; School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China., Fan SH; School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China., Li HY; School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China., Jin W; Department of Emergency Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China., Lu Y; Department of Emergency Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China. Electronic address: 0550@cdutcm.edu.cn. |
| Πηγή: | Journal of integrative medicine [J Integr Med] 2026 Jul; Vol. 24 (4), pp. 616-630. Date of Electronic Publication: 2026 Jan 28. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier B.V Country of Publication: Netherlands NLM ID: 101603118 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2095-4964 (Print) NLM ISO Abbreviation: J Integr Med Subsets: MEDLINE |
| Imprint Name(s): | Publication: Amsterdam : Elsevier B.V. Original Publication: [Beijing] : Science Press (China) |
| Ιατρικοί όροι (MeSH): | Lignans*/pharmacology , Lignans*/administration & dosage , Biphenyl Compounds*/pharmacology , Biphenyl Compounds*/administration & dosage , Sirtuin 3*/metabolism , Sirtuin 3*/genetics , Oxidative Phosphorylation*/drug effects , Pancreatitis*/metabolism , Pancreatitis*/drug therapy , Pancreatitis*/prevention & control , Pancreatitis*/genetics , Mitochondria*/metabolism , Mitochondria*/drug effects, Acetylation/drug effects ; Phenols ; Allyl Compounds ; Animals ; Mice ; Male ; Humans ; Mice, Inbred C57BL |
| Περίληψη: | Objective: Acute pancreatitis (AP) is a potentially life-threatening inflammatory disease with limited therapeutic options. Although honokiol has shown beneficial effects in animal models of AP, the mitochondrial mechanisms underlying these effects remain poorly understood. This study investigated whether honokiol protects against AP by activating the mitochondrial deacetylase sirtuin 3 (SIRT3) and regulating oxidative phosphorylation (OXPHOS) function. Methods: A mouse model of caerulein-induced AP was established to assess the temporal expression of SIRT3 and the effects of its pharmacological inhibition. The efficacy of honokiol was evaluated in vivo using an AP mouse model and in vitro using 266-6 cells and primary pancreatic acinar cells. Proteomic analysis was performed to identify SIRT3-regulated mitochondrial proteins and pathways. Protein-protein docking and immunoprecipitation were used to validate the interaction and acetylation of the respiratory complex subunits. Results: SIRT3 expression was markedly reduced in AP, while its inhibition exacerbated disease severity, confirming a protective role. Honokiol treatment restored SIRT3 expression, alleviated inflammation and mitochondrial damage, and partially rescued OXPHOS protein expression. The proteomic profiling identified three candidate OXPHOS subunits-adenosine triphosphate synthase membrane subunit K, cytochrome c1 (CYC1) and ubiquinol-cytochrome c reductase hinge protein-that were restored by honokiol treatment. The protein-protein docking analysis revealed strong binding affinity between SIRT3 and CYC1. The immunoprecipitation assay further confirmed that honokiol reduced the acetylation of CYC1, indicating that this effect is mediated by SIRT3 activity. Conclusion: Honokiol activates SIRT3 and promotes deacetylation of the respiratory complex Ⅲ subunit CYC1, contributing to OXPHOS restoration and mitochondrial protection in AP. These findings suggest a previously unrecognized SIRT3-CYC1 signaling axis underlying honokiol's mitochondrial protective effects in AP. Please cite this article as: Miao YF, Yao JQ, Peng Y, Bai D, Fan SH, Li HY, Jin W, Lu Y. Honokiol protects against acute pancreatitis by activating SIRT3 to restore mitochondrial oxidative phosphorylation and alleviate hyperacetylation. J Integr Med. 2026; 24(4):616-630. (Copyright © 2026 Shanghai Yueyang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. Published by Elsevier B.V. All rights reserved.) |
| Contributed Indexing: | Keywords: Acute pancreatitis; Cytochrome c1; Honokiol; Oxidative phosphorylation; Sirtuin3 |
| Substance Nomenclature: | 11513CCO0N (honokiol) 0 (Lignans) 0 (Phenols) 0 (Allyl Compounds) 0 (Biphenyl Compounds) EC 3.5.1.- (Sirtuin 3) |
| Entry Date(s): | Date Created: 20260208 Date Completed: 20260627 Latest Revision: 20260627 |
| Update Code: | 20260628 |
| DOI: | 10.1016/j.joim.2026.01.007 |
| PMID: | 41656152 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2095-4964 |
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| DOI: | 10.1016/j.joim.2026.01.007 |