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.
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