Research Paper Volume 13, Issue 7 pp 10326—10353
Carminic acid supplementation protects against fructose-induced kidney injury mainly through suppressing inflammation and oxidative stress via improving Nrf-2 signaling
- 1 Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, PR China
- 2 Research Center of Brain Intellectual Promotion and Development for Children Aged 0-6 Years, Chongqing University of Education, Chongqing 400067, PR China
- 3 Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, PR China
- 4 Department of Radiology, Linyi People Hospital, Linyi 276000, PR China
Received: February 25, 2020 Accepted: December 16, 2020 Published: April 4, 2021https://doi.org/10.18632/aging.202794
How to Cite
Copyright: © 2021 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Excessive fructose (Fru) intake has become an increased risk for chronic kidney disease progression. Despite extensive researches that have been performed to develop effective treatments against Fru-induced renal injury, the outcome has achieved limited success. In this study, we attempted to explore whether carminic acid (CA) could influence the progression of Fru-induced kidney injury, and the underlying molecular mechanism. At first, our in vitro results showed that CA significantly reduced inflammation in mouse tubular epithelial cells and human tubule epithelial cells stimulated by Fru. The anti-inflammatory effects of CA were associated with the blockage of nuclear factor-κB (NF-κB) signaling. In addition, Fru-exposed cells showed higher oxidative stress, which was effectively restrained by CA treatment through improving nuclear factor (erythroid-derived 2)-like 2 (Nrf-2) nuclear translocation. Importantly, we found that Fru-induced inflammation and oxidative stress were accelerated in cells with Nrf-2 knockdown. What’s more, in Fru-stimulated cells, CA-alleviated inflammatory response and reactive oxygen species (ROS) production were evidently abolished by Nrf-2 knockdown. The in vivo analysis demonstrated that Fru led to metabolic disorder, excessive albuminuria and histologic changes in renal tissues, which were effectively reversed by CA supplementation. We confirmed that CA significantly reduced inflammation and oxidative stress in the kidneys of mice through regulating NF-κB and Nrf-2 signaling pathways, eventually alleviating the progression of chronic kidney injury. Taken together, these results identified CA as a potential therapeutic strategy for metabolic stress-induced renal injury through restraining inflammation and oxidative stress via the improvement of Nrf-2 signaling.