Sci Rep. 2025 Apr 14;15(1):12759. doi: 10.1038/s41598-025-98079-9.
ABSTRACT
Diabetes mellitus, as a common chronic disease, easily leads to significant changes in the structure of the eye, among which diabetic cataract is particularly common. Although surgery is the main treatment for this complication, it may be accompanied by postoperative complications. Therefore, it is particularly important to develop specific drugs for diabetic cataract, aiming to fundamentally reduce its incidence and reduce the need for surgery. At present, the greatest challenge is to develop therapeutic agents with multiple synergistic effects based on the complex pathogenesis of cataract. 1-Acetyl-5-phenyl-1 H-pyrrol-3-ylacetate (APPA) is designed based on the pathological mechanism as a potential drug to alleviate the occurrence of diabetic cataract. Our observations suggest that APPA is more effective than bendazaclysine in alleviating high galactose-induced oxidative stress (The malondialdehyde content in the APPA group and bendazaclysine group was significantly reduced to 0.45-fold and 0.58-fold compared to the high galactose-induced group, respectively.) and apoptosis (The apoptosis rate in the APPA group and bendazaclysine group was significantly reduced to 0.28-fold and 0.35-fold compared to the high galactose-induced group, respectively.) in lens epithelial cells by increasing antioxidant enzyme activity, and restoring mitochondrial homeostasis. Mechanistic studies have shown that APPA restoration of mitochondrial homeostasis is mediated through the SIRT1-PGC-1α pathway. In the galactose-induced cataract rat model, APPA is effective in alleviating the occurrence of galactose-induced cataract. In conclusion, APPA with multiple synergistic functions may be a potential drug to alleviate the occurrence of diabetic cataract, and it has a wider range of indications than benzydalysine.
PMID:40229517 | DOI:10.1038/s41598-025-98079-9