Glaucocalyxin B Attenuates Diabetic Cardiomyopathy by Suppressing the NLRP3 Inflammasome and Restoring Gut Microbiota Homeostasis.

OBJECTIVES

Glaucocalyxin B (GLB) has documented anti-inflammatory activity in several disease contexts; however, its role in diabetic cardiomyopathy (DCM)-associated inflammatory injury remains insufficiently defined. In this study we aimed to evaluate whether GLB alleviates myocardial inflammation and injury in DCM and to explore the underlying mechanisms.

METHODS

We combined network pharmacology with experimental validation using a streptozotocin-induced diabetic rat model (8-week protocol) and high-glucose-challenged H9c2 rat cardiomyocytes. Oxidative stress-related indices (e.g. reactive oxygen species [ROS] and malondialdehyde [MDA]) and antioxidant capacity were assessed in vivo and in vitro. Gut microbiota composition was profiled by 16S rRNA sequencing. Activation of inflammatory signalling was evaluated with a focus on the nuclear factor-kappaB/NOD-like receptor pyrin domain-containing 3 (NFκB/NLRP3) axis.

RESULTS

Network pharmacology suggested that GLB targets were enriched in pathways related to cardiomyocyte regulation and DCM-associated processes, including inflammation, apoptosis, and oxidative stress responses. In both diabetic rat myocardium and high-glucose-treated H9c2 cells, GLB reduced oxidative stress burden, as evidenced by decreased ROS and MDA levels and improved antioxidant-related readouts. In addition, GLB was associated with increased gut microbial richness and diversity in diabetic rats. Mechanistically, GLB treatment was accompanied by suppression of NFκB/NLRP3 pathway activation, consistent with attenuation of inflammatory injury.

CONCLUSIONS

These findings provide initial evidence that GLB mitigates oxidative stress and inflammatory damage in DCM. The cardioprotective effects of GLB appear to involve modulation of the NFκB/NLRP3 signalling pathway and partial restoration of gut microbial diversity, supporting GLB as a promising candidate for further investigation in DCM.