Coptidis Rhizoma and Rheum officinale Supplementation Protects β-cells in Diabetic Rats by Suppressing the NLRP3 Inflammasome and Regulating the Gut Microbiota.

INTRODUCTION

Coptidis Rhizoma and Rheum Officinale (CR) are frequently used herbs in traditional Chinese medicine for managing Type 2 Diabetes Mellitus (T2DM). This study investigated the protective effects of CR on pancreatic β-cells in T2DM rats and elucidated the underlying mechanisms.

METHODS

A T2DM model was established using spontaneously diabetic Goto-Kakizaki (GK) rats. GK rats were administered varying doses of CR (low, mid, and high) for 8 weeks via gavage. After this period, changes in glycolipid levels, histopathology, insulin signalling pathways, NLRP3 inflammasome-related proteins, and gut microbiota were examined.

RESULTS

CR treatment exerted modulatory effects on glucolipid metabolism disorders in GK rats, ameliorating histopathological injury to the pancreas. It increased insulin-positive cell expression and secretion, reduced cell death, lowered the levels of NLRP3, ASC, and caspase 1 proteins, and enhanced insulin signal transduction. Additionally, it regulated gut microbiota, promoting microbiota richness and diversity and restructuring its equilibrium at various taxonomic levels, including the phylum and genus levels.

DISCUSSION: Our results demonstrate that CR supplementation concurrently suppresses the NLRP3 inflammasome pathway and modulates the gut microbiota, both of which are implicated in β-cell protection. While the precise interplay between these two systems in the context of CR treatment requires further investigation, the coordinated suppression of inflammation and amelioration of gut dysbiosis highlight a potential multi-targeted mechanism of action for this herbal formulation, which aligns with the holistic principles of traditional Chinese medicine.

CONCLUSION

CR exerts protective effects on pancreatic β-cells, which are associated with the suppression of NLRP3 inflammasome activation-mediated inflammatory responses and modulation of gut microbiota.