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

Abstract

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.