Honokiol Alleviates Dry Eye-Related Corneal Epithelial Damage by Activating SIRT3/PINK1-Mediated Mitophagy.

Authors

Yulei Huang, Xindan Cao, Xinlin Yan, Jiaqi Lin, Zhengyu Cao, Xiafei Chen, Jiahao Zhu, Yi Guan, Guozhen Chen, Xuan Li

Published in

Drug design, development and therapy. Volume 20. Pages 622482. Epub Sep 22, 2026.

Abstract

Dry eye is a common ocular surface disease characterized by corneal epithelial damage, yet effective therapies targeting mitochondrial dysfunction remain limited.
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.
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.
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.
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.

PMID:
42801105
Bibliographic data and abstract were imported from PubMed on 27 Sep 2026.

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