Protective efficacy and mechanism of gypenosides against diabetic cataracts via the ferroptosis pathway: A study based on network pharmacology.

Abstract

Gypenosides (GPs), extracted from the traditional Chinese herb Gynostemma pentaphyllum (Thunb.) Makino, have exhibited a wide range of pharmacological effects, including anticancer, anti-obesity, lipid-improving, anti-inflammatory, and neuroprotective properties, in addition to being used in treating diabetes mellitus and lipid metabolism disorder. Although these pharmacological properties suggest the potential for diabetic cataracts (DC) treatment, it is unclear whether Gynostemma has protective effects against DC and the possible mechanisms involved. Previous studies have confirmed the respective relations between ferroptosis and diabetes mellitus,diabetic complications. To investigate the protective effects of GPs on DC from the perspective of ferroptosis, and to explore the potential regulatory pathways and mechanisms. A diabetic rat model was established and treated with GPs. PPI network were constructed to obtain the hub targets. The biological functions and potential pathways were analyzed through GO and KEGG enrichment. Molecular docking, ELISA was used to verify the interactions between Gynostemma and the key targets and the reliability of the targets. HE staining was performed to observe the pathomorphological alterations. The kit, IHC and western blot was performed to evaluate the expression of MDA,SOD,GSH, total iron content, ICAM-1,and the ferroptosis-related proteins of SLC7A11/GPX4/P53 signaling pathway in the lens tissue. The study highlighted the effects of Gynostemma in reducing crystalline pathomorphological changes and mitigating ferroptosis in diabetic cataracts. It further suggested that these protective effects may be achieved through the regulation of the ferroptosis-related P53/SLC7A11/GPX4 pathway.