Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Sep 15, 2023; 14(9): 1349-1368
Published online Sep 15, 2023. doi: 10.4239/wjd.v14.i9.1349
Genipin relieves diabetic retinopathy by down-regulation of advanced glycation end products via the mitochondrial metabolism related signaling pathway
Ke-Xin Sun, Yan-Yi Chen, Zhen Li, Shi-Jie Zheng, Wen-Juan Wan, Yan Ji, Ke Hu
Ke-Xin Sun, Yan-Yi Chen, Shi-Jie Zheng, Wen-Juan Wan, Yan Ji, Ke Hu, Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
Zhen Li, Department of Ophthalmology, The People’s Hospital of Leshan, Leshan 400000, Sichuan Province, China
Author contributions: Sun KX and Hu K were involved in design and conduct of the study, and preparation of the manuscript; Sun KX, Chen YY, and Li Z participated in the collection of the data; Zheng SJ, Wan WJ, Ji Y, and Hu K participated in the management of this program; all authors have read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 81870650, No. 81570832, and No. 81900885; Science and Technology Program Chongqing, No. 2018GDRC008 and No. XKTS049.
Institutional animal care and use committee statement: All animal experimental protocols were reviewed and approved by the Institutional Animal Care and Use Committee of Chongqing Medical University (No. 2022-K45).
Conflict-of-interest statement: None of the authors have any financial/conflicting interests to disclose.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author Professor Ke Hu at 42222@qq.com.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ke Hu, Doctor, MD, Chief Doctor, Doctor, Professor, Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing 400016, China. 42222@qq.com
Received: March 3, 2023
Peer-review started: March 3, 2023
First decision: April 26, 2023
Revised: May 4, 2023
Accepted: August 7, 2023
Article in press: August 7, 2023
Published online: September 15, 2023
Processing time: 194 Days and 0.5 Hours
ARTICLE HIGHLIGHTS
Research background

Diabetic retinopathy (DR) is a serious and common complication of diabetes. Advanced glycation end products (AGEs) are a group of reversible and poisonous products formed by nonenzymatic glycation of glucose with protein and lipids under hyperglycemia conditions. Both acute and chronic hyperglycemia can enhance AGEs production, which results in endothelial dysfunction and causes severe damage to diabetic retina. Some traditional Chinese herb like Gardenia jasminoides Ellis (GJE) fruit is a selective inhibitor of AGEs.

Research motivation

To confirm the effect of genipin, a vital component of GJE fruit, in preventing human retinal microvascular endothelial cells (hRMECs) from AGEs damage in DR and explored its mechanism.

Research objectives

To demonstrate whether genipin could lessen the development of DR in experimental models (4-wk-old C57/BL6 mice) through AGEs inhibition.

Research methods

Cell Counting Kit-8 (CCK-8) assay, colony formation assay, flow cytometry, immunofluorescence, wound healing assay, transwell assay, and tube-forming assay were used to detect the effect of genipin on hRMECs in vivo. Streptozotocin induced mice were used to explore retinal dysfunction with DM in vitro. Reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose assays were used to evaluate energy metabolism and oxidative stress damage in high glucose-induced hRMECs and STZ mouse retinas. Immunofluorescence and Western blot were used to investigate the expression of inflammatory cytokines (VEGF, SCG3, TNF-α, IL-1β, IL-18, and NLRP3).

Research results

Our study confirmed that genipin ameliorated AGEs-induced hRMECs proliferation, apoptosis, energy metabolism, oxidative stress, and inflammatory injury, partially via the CHGA/UCP2/glucose transporter 1 pathway. Control of AGEs by IOI of genipin may represent a strategy to prevent severed retinopathy and vision loss.

Research conclusions

Our study suggested that intraocular injection of genipin can ameliorate AGEs to control DR. Control of AGEs and using principal bioactive components extracted from herb by intraocular injection may represent strategies to prevent DR.

Research perspectives

Our future work will focus on the changes in SCG3 during abnormal physiological processes.