Epigallocatechin‐3‐Gallate Ameliorates Diabetic Kidney Disease by Inhibiting the TXNIP/NLRP3/IL‐1β Signaling Pathway

ABSTRACT Recent research indicates that the activation of the NLRP3 inflammasome is crucial in the development of diabetic kidney disease (DKD). Epigallocatechin‐3‐gallate (EGCG), the predominant catechin in green tea, has been noted for its anti‐inflammatory properties in DKD. However, the specific mechanisms are not yet fully understood. In this study, our objective was to explore the effects of EGCG on podocytes and in diabetic kidney disease (DKD) mice and investigate how EGCG modulates the TXNIP/NLRP3/IL‐1β signaling pathway in DKD, both in podocytes and animal models. In vitro, we co‐cultured podocytes with EGCG and detected the viability, apoptosis, inflammation and the TXNIP/NLRP3/IL‐1β signaling pathway. In vivo, DKD mice were given EGCG via oral gavage, followed by evaluations of renal function, inflammation, and the aforementioned signaling pathway. Our findings revealed that oxidative stress, inflammatory cytokines, and the TXNIP/NLRP3/IL‐1β pathway were upregulated in podocytes exposed to high glucose (HG) and in the kidneys of DKD mice. However, EGCG treatment reduced the expression of the NLRP3 inflammasome and its associated proteins, including TXNIP, ASC, caspase‐1, and IL‐1β, as well as the levels of ROS and inflammatory factors such as TNF‐α, IL‐6, and IL‐18. Furthermore, in vivo, EGCG improved kidney function, reduced albuminuria and body weight, and alleviated renal pathological damage. In summary, our study suggests that EGCG mitigates inflammation in podocytes and DKD through the TXNIP/NLRP3/IL‐1β signaling pathway, indicating potential benefits of EGCG or green tea in managing DKD.