Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Drug Targeting and Drug Delivery System Key Laboratory of Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
Huijun Liu
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Drug Targeting and Drug Delivery System Key Laboratory of Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
Xingli Huo
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Drug Targeting and Drug Delivery System Key Laboratory of Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
Junlong Chen
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Drug Targeting and Drug Delivery System Key Laboratory of Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
Yu Li
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Drug Targeting and Drug Delivery System Key Laboratory of Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
Yu Huang
Haisco Pharmaceutical Group Co., Ltd., Chengdu 611130, China
Zongning Yin
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Drug Targeting and Drug Delivery System Key Laboratory of Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
Acute kidney injury (AKI) is a condition with a poor prognosis, exacerbated by the lack of effective therapeutic options and inadequately understood underlying mechanisms. Glycosylation, a post-translational modification of proteins, is essential for maintaining protein stability and function, and its dysregulation leads to protein misfolding and amyloid aggregation. Glycosylation dynamics are implicated in several pathologies, including inflammation, cancer, and AKI, highlighting the therapeutic potential of regulating glycosylation and preventing aggregation in AKI treatment. This study investigates the effect of nafamostat mesylate (NM) on protein glycosylation and amyloid aggregation in vivo. Using optical spectroscopy and other analytical techniques, we demonstrate that NM restores glycosylation levels and inhibits protein aggregation in aristolochic-acid-induced acute kidney injury. The mechanism likely involves enzymatic modulation that corrects hypoglycosylation and prevents amyloid aggregation, promoting proper protein folding and enhancing its stability. These findings suggest that NM may provide a novel therapeutic strategy for AKI and other glycosylation-related diseases, underscoring the potential for early intervention and treatment of these conditions.