Loganin reduces diabetic kidney injury by inhibiting the activation of NLRP3 inflammasome-mediated pyroptosis.

Abstract

Diabetic kidney disease (DKD) is an essential cause of end-stage renal disease. The ongoing inflammatory response in the proximal tubule promotes the progression of DKD. Timely and effective blockade of the inflammatory process to protect the kidney during DKD progression is a proven strategy. The purpose of this study was to investigate the protective effect of loganin on diabetic nephropathy in vivo and in vitro and whether this effect was related to the inhibition of pyroptosis. The results indicated that loganin reduced fasting blood glucose, blood urea nitrogen and serum creatinine concentrations, and alleviated renal pathological changes in DKD mice. In parallel, loganin downregulated the expression of pyroptosis related proteins in the renal tubules of DKD mice and decreased serum levels of interleukin-1beta (IL-1β) and interleukin-18 (IL-18). Furthermore, in vitro experiments showed that loganin attenuated high glucose-induced HK-2 cell injury by reducing the expression of pyroptosis-related proteins, and cytokine levels were also decreased. These fundings were also confirmed in the polyphyllin VI (PPVI) -induced HK-2 cell pyroptosis model. Loganin reduces high glucose induced HK-2 cells pyroptosis by inhibiting reactive oxygen species (ROS) production and NOD-like receptor protein 3 (NLRP3) inflammasome activation. In conclusion, the inhibition of pyroptosis via inhibition of the NLRP3/Caspase-1/Gasdermin D (GSDMD) pathway might be an essential mechanism for loganin treatment of DKD.

• Authors: Xiangri Kong, Yunyun Zhao, Xingye Wang, Yongjiang Yu, Ying Meng, Guanchi Yan, Miao Yu, Lihong Jiang, Wu Song, Bingmei Wang, Xiuge Wang
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 382 Pg. 110640 (Sep 01 2023) ISSN: 1872-7786 [Electronic] Ireland
• PMID: 37473909 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 Elsevier B.V. All rights reserved.

Chemical References

• Inflammasomes
• NLR Family, Pyrin Domain-Containing 3 Protein
• loganin
• NLR Proteins
• Glucose

Topics

• Mice
• Animals
• Inflammasomes (metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Pyroptosis
• NLR Proteins
• Diabetic Nephropathies (drug therapy)
• Kidney (metabolism)
• Glucose (pharmacology)
• Diabetes Mellitus