Genipin relieves diabetic retinopathy by down-regulation of advanced glycation end products via the mitochondrial metabolism related signaling pathway

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.