Chen's Jinshui Pills ameliorate diabetic retinopathy in mice and are associated with intestinal barrier protection and anti-inflammatory effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Chen's Jinshui Pills (CJSP), a traditional Chinese medicinal formula, is commonly used to treat ophthalmic disorders. However, its therapeutic effects and mechanisms in diabetic retinopathy (DR) require further validation and exploration.

AIM OF THE STUDY: In this study, we investigated the protective effects of CJSP on DR and its association with intestinal homeostasis.

MATERIALS AND

METHODS

A type 2 diabetic mouse model was established and treated with CJSP. Metabolic parameters and retinal pathology were evaluated. Mass spectrometry and network pharmacology were applied to identify targets and pathways. Intestinal barrier function was assessed by histology and protein expression. Fecal microbiota sequencing and metabolomics were integrated, and PPARγ-related mechanisms were experimentally validated.

RESULTS

In diabetic mice, CJSP reduced blood glucose, alleviated body weight loss, decreased gray-white retinal lesion areas, and increased retinal thickness. Mass spectrometry and network pharmacology analyses indicated strong anti-inflammatory activity of CJSP, involving IL-6, TNF-α, and IL-17 pathways, which was experimentally validated. CJSP improved intestinal homeostasis by increasing colonic goblet cells, upregulating ZO-1 and Occludin, and downregulating EEA1 and Rab7, indicating enhanced barrier integrity. Integrated microbiota and metabolomics analyses revealed elevated beneficial metabolites, particularly DHA, and identified specific bacterial taxa potentially involved in DHA metabolism. As a natural PPARγ ligand, DHA supports PPARγ as a key target. Further experiments suggested that CJSP may activate PPARγ signaling to protect the intestinal barrier and suppress intestinal inflammation.

CONCLUSION

CJSP ameliorates DR progression, which may involve modulation of microbial metabolism, intestinal barrier function, and gut-derived inflammation.