Chicoric Acid Attenuated Renal Tubular Injury in HFD-Induced Chronic Kidney Disease Mice through the Promotion of Mitophagy via the Nrf2/PINK/Parkin Pathway

As the main factor in the pathogenesis of chronic kidney disease (CKD), the excessive apoptosis of renal tubular epithelial cells (RTECs) and its underlying mechanism of action are worth further investigation. Chicoric acid (CA), a major active constituent of the Uyghur folk medicine chicory, was re...

Full description

Saved in:
Bibliographic Details
Published in:Journal of agricultural and food chemistry 2022-03, Vol.70 (9), p.2923-2935
Main Authors: Ding, Xiao-qin, Jian, Tun-yu, Gai, Ya-nan, Niu, Guan-ting, Liu, Yan, Meng, Xiu-hua, Li, Jing, Lyu, Han, Ren, Bing-ru, Chen, Jian
Format: Article
Language:English
Subjects:
Animals
Bioactive Constituents, Metabolites, and Functions
Caffeic Acids
Diet, High-Fat - adverse effects
Hyperuricemia - metabolism
Mice
Mice, Inbred C57BL
Mitochondria - metabolism
Mitophagy
NF-E2-Related Factor 2 - genetics
NF-E2-Related Factor 2 - metabolism
Renal Insufficiency, Chronic - etiology
Renal Insufficiency, Chronic - genetics
Succinates
Ubiquitin-Protein Ligases - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:As the main factor in the pathogenesis of chronic kidney disease (CKD), the excessive apoptosis of renal tubular epithelial cells (RTECs) and its underlying mechanism of action are worth further investigation. Chicoric acid (CA), a major active constituent of the Uyghur folk medicine chicory, was recorded to possess a renal protective effect. The precise effect of CA on renal tubular injury in obesity-related CKD remains unknown. In the current study, CA was proven to ameliorate metabolic disorders including overweight, hyperglycemia, hyperlipidemia, and hyperuricemia in high fat diet (HFD)-fed mice. Furthermore, the reverse effect of CA on renal histological changes and functional damage was confirmed. In vitro, the alleviation of lipid accumulation and cell apoptosis was observed in palmitic acid (PA)-exposed HK2 cells. Treatment with CA reduced mitochondrial damage and oxidative stress in the renal tubule of HFD-fed mice and PA-treated HK2 cells. Finally, CA was observed to activate the Nrf2 pathway; increase PINK and Parkin expression; and regulate LC3, SQSTM1, Mfn2, and FIS1 expression; therefore, it would improve mitochondrial dynamics and mitophagy to alleviate mitochondrial damage in RTECs of obesity-related CKD. These results may provide fresh insights into the promotion of mitophagy in the prevention and alleviation of obesity-related CKD.
ISSN:0021-8561
1520-5118
DOI:10.1021/acs.jafc.1c07795