Genipin ameliorates diabetic retinopathy via the HIF-1α and AGEs-RAGE pathways
•Network pharmacology was used to selected a Traditional Chinese medicine and its active monomer to treat disease.•Genipin against diabetic retinopathy via the HIF-1α and AGEs-RAGE pathways.•Genipin regulates angiogenesis, and reduces ROS and inflammation in hRMECs.•Genipin protects cells by mediati...
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Veröffentlicht in: | Phytomedicine (Stuttgart) 2024-07, Vol.129, p.155596, Article 155596 |
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Zusammenfassung: | •Network pharmacology was used to selected a Traditional Chinese medicine and its active monomer to treat disease.•Genipin against diabetic retinopathy via the HIF-1α and AGEs-RAGE pathways.•Genipin regulates angiogenesis, and reduces ROS and inflammation in hRMECs.•Genipin protects cells by mediating phosphorylation and glycosylation.
Traditional Chinese medicine (TCM) is useful in disease treatment and prevention. Genipin is an active TCM compound used to treat diabetic retinopathy (DR). In this study, a network pharmacology (NP)-based approach was employed to investigate the therapeutic mechanisms underlying genipin administration in DR.
The potential targets of DR were identified using the gene expression omnibus (GEO) database. TCM database screening and NP were used to predict the potential active targets and pathways of genipin in DR. Cell viability was tested in vitro to determine the effects of different doses of glucose and genipin on Human Retinal Microvascular Endothelial Cells (hRMECs). CCK-8, CCK-F, colony formation, CellTiter-Lum, Annexin V-FITC, wound healing, Transwell, tube-forming, reactive oxygen species (ROS), and other assay kits were used to detect the effects of genipin on hRMECs during high levels of glucose. In vivo, a streptozotocin (STZ)-mouse intraocular genipin injection (IOI.) model was used to explore the effects of genipin on diabetes-induced retinal dysfunction. Western blotting was performed to identify the cytokines involved in proliferation, apoptosis, angiogenesis, ROS, and inflammation. The protein expression of the AKT/ PI3K/ HIF-1α and AGEs/ RAGE pathways was also examined.
Approximately 14 types of TCM, and nearly 300 active ingredients, including genipin, were identified. The NP approach successfully identified the HIF-1α and AGEs-RAGE pathways, with the EGR1 and UCP2 genes, as key targets of genipin in DR. In the in vitro and in vivo models, we discovered that high glucose increased cell proliferation, apoptosis, angiogenesis, ROS, and inflammation. However, genipin application regulated cell proliferation and apoptosis, inhibited angiogenesis, and reduced ROS and inflammation in the HRMECs exposed to high glucose. Furthermore, the retinal thickness in the genipin-treated group was lower than that in the untreated group. AKT/ PI3K/ HIF-1α and AGEs/ RAGE signaling was increased by high glucose levels; however, genipin treatment decreased AKT/ PI3K and AGEs/ RAGE pathway expressions. Genipin also increased HIF-1α p |
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ISSN: | 0944-7113 1618-095X 1618-095X |
DOI: | 10.1016/j.phymed.2024.155596 |