ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1593213
This article is part of the Research TopicNatural Medicines for Metabolic Diseases – Computational and Pharmacological Approaches, Volume IIView all articles
Targeting Mitophagy in Diabetic Retinopathy: Novel Insights into SQSTM1/BNIP3L Pathway Regulated by Luteolin
Provisionally accepted
- Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Objective: Diabetic retinopathy (DR) is a leading microvascular complication of diabetes. Luteolin, a flavonoid with known anti-inflammatory and antioxidant properties, has demonstrated therapeutic potential in early investigations for the treatment of DR. However, its precise molecular mechanisms remain inadequately defined. This study aimed to explore the local and systemic immunological mechanisms underlying luteolin's therapeutic effects on DR.Methods: Key regulatory genes and cell subpopulations were identified from single-cell RNA sequencing (scRNA-Seq) datasets derived from peripheral blood mononuclear cells (PBMCs) and retinal tissues of DR patients. The molecular interactions were analyzed using molecular docking simulations. Reactive oxygen species (ROS) were quantified through DCFDA assays, while retinal structural damage was assessed using Hematoxylin and eosin (H&E) and Periodic Acid-Schiff (PAS) staining. Comprehensive analyses, including enzyme-linked immunosorbent assays (ELISA), immunofluorescence, immunohistochemistry, and Western blotting were conducted to evaluate cytokine levels and protein expression.The study revealed that luteolin exerted protective effects against DR primarily by activating mitophagy and reducing oxidative stress, with the SQSTM1/BNIP3L pathway emerging as a critical mediator. Furthermore, a novel mechanistic link was established between monocyte activity and DR progression, highlighting the VISFATIN signaling pathway's role in immune cell regulation and its contribution to disease pathology.This study offers novel insights into the luteolin's therapeutic potential in DR, particularly activating mitophagy through the SQSTM1/BNIP3L axis, which expands the scope of natural compounds in addressing this sight-threatening complication of diabetes.
Keywords: Diabetic Retinopathy, Monocytes, Sqstm1, Bnip3L, Luteolin
Received: 13 Mar 2025; Accepted: 11 Jun 2025.
Copyright: © 2025 Zhang, Wu and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yinjian Zhang, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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