PAKISTAN
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6-Gingerol Alleviates Acute Kidney Injury in Mice Via Activating Ampk/Nlrp3 Axis
 
Qian Zhao1#, Xiaoming Yin1# , Shuang Chang2, Chengyi Che2, Tengfei Wu3*, Feifei Sun4* and Yixin Chen4*

1Department of Pediatric Urology, Shengjing Hospital of China Medical University, Shenyang 110004, China; 2Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Taian 271017, Shandong Province, China; 3Department of Laboratory Animal Science, China Medical University, Shenyang, 110122, China; 4Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang 110004, China. # Qian Zhao and Xiaoming Yin contributed to the work equally.

*Corresponding author: 20192107@cmu.edu.cn (Chen Y); sffecho0120@163.com (Sun F); tfwu@cmu.edu.cn (Wu T)

Abstract   

Acute kidney injury (AKI) commonly occurs following ischemia-reperfusion (I/R) during surgery or transplantation, and effective pharmacological treatments are limited. This study investigated the reno-protective effects and underlying mechanisms of 6-gingerol (6-G) in experimental mice of I/R-induced AKI. Renal I/R injury was induced in mice by bilateral renal pedicle clamping for 25 minutes followed by 24 hours of reperfusion. During reperfusion, mice received intragastric administration of 6-gingerol (50, 100 and 200mg/kg) every 8 hours. Renal function was evaluated by serum creatinine and blood urea nitrogen levels. Histopathological changes were assessed using hematoxylin and eosin and periodic acid–Schiff staining. Inflammatory responses were analyzed by measuring renal mRNA expression of interleukin-1β, interleukin-18, interleukin-6, and tumor necrosis factor-α. The expression of kidney injury markers (NGAL and KIM-1), inflammasome components (NLRP3, ASC & cleaved caspase-1) and phosphorylated/total AMP-activated protein kinase (AMPK) was examined using western blotting, immunohistochemistry, and immunofluorescence. 6-G treatment significantly improved renal function and attenuated tubular injury and glycogen deposition. It also markedly suppressed inflammatory cytokine expression and macrophage infiltration (P<0.01). Mechanistically, 6-G inhibited activation of the NLRP3/ASC/caspase-1 inflammasome while restoring AMPK phosphorylation. Notably, these protective effects were abolished by the AMPK inhibitor Compound C, indicating an AMPK-dependent mechanism. The findings demonstrated that 6-G alleviates renal dysfunction and tissue injury in I/R-induced AKI by activating AMPK and suppressing NLRP3 inflammasome-mediated inflammation, highlighting its therapeutic potential for AKI management.

To Cite This Article: Zhao Q, Yin X, Chang S, Che C, Wu T, Sun F and Chen Y, 2025. 6-Gingerol alleviates acute kidney injury in mice via activating ampk/nlrp3 axis. Pak Vet J, 45(4): 1980-1987. http://dx.doi.org/10.29261/pakvetj/2025.xxx

 
 
   
 

ISSN 0253-8318 (Print)
ISSN 2074-7764 (Online)



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