Functions of dendrobine in a zebrafish model of diabetic retinopathy

Dendrobine (DEN), an alkaloid isolated from Dendrobium species, is widely used in diabetes management. However, its therapeutic potential against high-glucose-induced diabetic retinopathy (DR) has not been explored. This study used zebrafish (Danio rerio) as a model to investigate the protective effects of DEN on high-glucose-induced DR and to elucidate its underlying mechanisms.

The effects of DEN were evaluated using transgenic zebrafish lines, with hematoxylin and eosin (HE) staining of ocular tissues to assess retinal morphology. Behavioral tracking quantified locomotor function. RNA sequencing was performed to identify co-differentially expressed genes (DEGs), characterize common signaling pathways, and construct protein-protein interaction (PPI) networks. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used for validation.

DEN significantly alleviated high-glucose-induced retinal damage, improved physiological development, and restored locomotor function. Transcriptomic analysis of zebrafish treated with 20 mg/L and 40 mg/L DEN + glucose identified 80 commonly reversed DEGs, significantly enriched in retinol metabolism, steroid hormone biosynthesis, porphyrin metabolism, and PPAR signaling pathway. Notably, shared genes such as ugt1a1, ugt2a2, ugt2b1, and ugt5a2 were downregulated across the retinol metabolism, steroid hormone biosynthesis, and porphyrin metabolism pathways.

This study provides novel morphological and transcriptomic evidence that DEN mitigates high-glucose-induced DR in a zebrafish model. The findings highlight DEN's therapeutic potential and offer new insights into the application of traditional Chinese medicine for DR treatment.