論文 - 詳細
| RRC ID | 90003 |
|---|---|
| 著者 | Huang Y, Cao X, Yan X, Lin J, Cao Z, Chen X, Zhu J, Guan Y, Chen G, Li X. |
| タイトル | Honokiol Alleviates Dry Eye-Related Corneal Epithelial Damage by Activating SIRT3/PINK1-Mediated Mitophagy. |
| ジャーナル | Drug Des Devel Ther |
| Abstract |
BACKGROUND:Dry eye is a common ocular surface disease characterized by corneal epithelial damage, yet effective therapies targeting mitochondrial dysfunction remain limited. PURPOSE:To investigate the protective effects of honokiol (HKL) against dry eye-related corneal epithelial injury and elucidate the underlying mechanisms focusing on SIRT3 and PINK1-mediated mitophagy. METHODS:A benzalkonium chloride (BAC)-induced dry eye mouse model (n=6) was established and treated with HKL eye drops. Corneal damage was assessed by slit-lamp photography, Schirmer I test, and H&E staining. SIRT3, PINK1, and mitophagy-related proteins were examined by immunofluorescence and Western blot. Human corneal epithelial cells (HCECs) were exposed to hyperosmolar stress with or without HKL (n=5). Cell viability, oxidative stress, mitochondrial morphology, and function were evaluated. PINK1 knockdown was performed to validate its role in HKL-mediated protection. RESULTS:In both BAC-induced mice and hyperosmolar-stressed HCECs, SIRT3 was downregulated with activation of PINK1/Parkin-mediated mitophagy, accompanied by mitochondrial dysfunction, apoptosis (increased to 36.2%, P < 0.001), and inflammation. HKL treatment restored mitochondrial dynamics balance, enhanced PINK1-dependent mitophagy, and alleviated oxidative stress, apoptosis (reduced to 17.4%, P < 0.001), and inflammation. PINK1 knockdown abrogated these protective effects, confirming PINK1 as a key mediator. Notably, HKL primarily enhanced SIRT3 activity rather than its expression, as immunofluorescence showed partial SIRT3 recovery in the corneal epithelium while Western blot showed no statistical significance. In vivo, HKL improved corneal integrity, tear secretion (from 1.8 to 3.5 mm/2min, P < 0.01), and tissue structure, consistent with in vitro findings. CONCLUSION:This study demonstrates that HKL protects against dry eye-associated corneal epithelial damage potentially through a mechanism involving SIRT3 modulation and PINK1-mediated mitophagy, offering a potential therapeutic strategy for dry eye disease. |
| 巻・号 | 20 |
| ページ | 622482 |
| 公開日 | 2026-1-1 |
| DOI | 10.2147/DDDT.S622482 |
| PII | 622482 |
| PMID | 42801105 |
| PMC | PMC13615808 |
| MeSH | Allyl Compounds Animals Biphenyl Compounds* / administration & dosage Biphenyl Compounds* / pharmacology Cells, Cultured Disease Models, Animal Dose-Response Relationship, Drug Dry Eye Syndromes* / drug therapy Dry Eye Syndromes* / metabolism Dry Eye Syndromes* / pathology Epithelium, Corneal* / drug effects Epithelium, Corneal* / metabolism Epithelium, Corneal* / pathology Humans Lignans* / administration & dosage Lignans* / pharmacology Male Mice Mice, Inbred C57BL Mitophagy* / drug effects Oxidative Stress / drug effects PTEN-Induced Putative Kinase Phenols Protein Kinases* / metabolism Sirtuin 3* / metabolism |
| リソース情報 | |
| ヒト・動物細胞 | HCE-T(RCB2280) |