Urolithin A alleviates acute kidney injury induced by renal ischemia reperfusion through the p62‐Keap1‐Nrf2 signaling pathway

Zhang, Yi; Liu, Mengmeng; Zhang, Yaoyuan; Mao, Tian; Chen, Peng; Yu, Lian; Zhou, Benhong

doi:10.1002/ptr.7370

Cited by 21 publications

(21 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A chronic fructose diet is a risk factor for hyperuricemic nephropathy. Urolithin A (UroA) is one of the major natural intestinal metabolites of ellagitannins found in pomegranates, berries, nuts, etc., with various pharmacological potentials ( Cheng et al, 2021 ; Zhang et al, 2022 ). However, the beneficial effect of UroA against hyperuricemic nephropathy and the underlying mechanism needs further investigation.…”

Section: Discussionmentioning

confidence: 99%

Urolithin A Attenuates Hyperuricemic Nephropathy in Fructose-Fed Mice by Impairing STING-NLRP3 Axis-Mediated Inflammatory Response via Restoration of Parkin-Dependent Mitophagy

et al. 2022

Self Cite

View full text Add to dashboard Cite

Urolithin A (UroA) is one of the primary intestinal metabolites of ellagitannins, showing translational potential as a nutritional intervention in humans. Mounting evidence suggests that fructose consumption contributes to the progression of chronic kidney disease (CKD) that manifests in hyperuricemic nephropathy, renal inflammation, and tubulointerstitial injury. Here, we investigated the efficacy of UroA in alleviating fructose-induced hyperuricemic nephropathy in mice. Uric acid-exposed human kidney-2 (HK-2) cells were utilized for in vitro mechanism validation. Histopathological staining, immunoblotting, and transmission electron microscope were performed for the mechanistic investigations. Our results revealed that UroA ameliorated fructose-induced hyperuricemic nephropathy in mice. The histopathologic assessment showed that UroA attenuated tubular hypertrophy and dilation, glomerular basement membrane thickening, and collagen deposition in the kidney of fructose-fed mice. Mechanistically, UroA treatment impaired STING-NLRP3 activation, resulting in reduced production of proinflammatory cytokines IL-1β, IL-6, and TNF-α. Notably, UroA exhibited a scavenging effect against reactive oxygen species (ROS) and restored fructose-impaired PINK1/Parkin-mediated mitophagy in nephropathic mice. Furthermore, the inhibitory effect of UroA in STING-NLRP3 activation was impaired after Parkin gene silencing in HK-2 cells. Together, this study suggests that UroA alleviates fructose-induced hyperuricemic nephropathy by promoting Parkin-dependent mitophagy, thereby suppressing STING-NLRP3 axis-mediated inflammatory response. Thus, dietary supplementation with UroA or ellagitannins-rich foods may serve as a promising intervention to prevent CKD progression.

show abstract

Section: Discussionmentioning

confidence: 99%

Urolithin A Attenuates Hyperuricemic Nephropathy in Fructose-Fed Mice by Impairing STING-NLRP3 Axis-Mediated Inflammatory Response via Restoration of Parkin-Dependent Mitophagy

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…Dai et al found Scu led to up-regulation of HO-1 through activating the Nrf2 signalling pathway, protecting the kidneys from ischemia/reperfusion (I/ R)-induced oxidative damage (35). Zhang et al Studies demonstrated that UA can alleviate oxidative stress and promote autophagy by activating the p62-Keap1-Nrf2 signaling pathway, which could protect the kidneys from ischemia reperfusion injury (36). In the Nrf2/ARE/HO-1 signaling pathway, Nrf2 regulates the expression of HO-1 by binding to ARE (37).…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV protects against ischemia/reperfusion (I/R)-induced kidney injury based on the Keap1-Nrf2/ARE signaling pathway

Y¹,

Chen²,

Feng³

et al. 2022

Transl Androl Urol

View full text Add to dashboard Cite

Background: This study sought to investigate the protective effects of Astragaloside IV (AS-IV) on ischemia-reperfusion (I/R) renal injury based on the keap1-Nrf2/ARE signaling pathway.Methods: A total of 36 male Sprague-Dawley rats (aged: 8 weeks; weighing: 200-220 g) were randomly divided into the following 6 groups (n=6 per group): (I) the control group; (II) the sham operation group;(III) the kidney I/R injury group (the I/R group); (IV) the kidney I/R injury group treated with 2 mg/kg of AS-IV (the low-dose group); (V) the kidney I/R injury group treated with 5 mg/kg of AS-IV (the mid-dose group); and (VI) the kidney I/R injury group treated with 10 mg/kg of AS-IV (the high-dose group). Serum creatinine (CRE), serum urea, malondialdehyde (MDA), and superoxide dismutase (SOD) were examined using enzyme-linked immunoassay kits. Cell apoptosis and the pathological damage to the renal tissue were determined by terminal deoxynucleotidyl transferase dUTP nick end labeling, hematoxylin and eosin, and periodic acid-Schiff (PAS) staining. The immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR), and western blot methods were used to determine the expression of Nrf2, HO-1, Bcl-2 and Bax in the kidney tissue.Results: In the I/R rat model, the serum CRE level was increased. In the acute kidney injury (AKI) and chronic kidney disease (CKD) models, AS-IV treatment significantly decreased serum CRE levels in a dosedependent manner. AS-IV treatment also reduced the injury of renal tubular epithelial cells, increased the expression levels of Nrf2 and HO-1, decreased the rate of apoptosis, downregulated the level of MDA, and elevated the activity of SOD. In the CKD rat model, the AS-IV treatment groups had reduced renal tubular epithelial cell injury, increased expression levels of Nrf2 and HO-1, decreased MDA levels, and increased SOD activity compared to the I/R group.Conclusions: AS-IV induced the expression of Nrf2, enhanced the activity of antioxidant enzymes, reduced apoptosis, protected against renal I/R injury, and prevented AKI from transforming into CKD.These findings suggest that AS-IV is a promising drug for treating kidney injury.

show abstract

“…Accumulated evidences have shown that urolithin A exhibits multiple protective effects inducing mitophagy in heart ( Huang et al, 2022c ), muscle ( Luan et al, 2021 ) and brain ( Jayatunga et al, 2021 ). As a Nrf2 activator, urolithin A not only protects kidney against oxidative stress via promoting Nrf2 translocating into nucleus ( Zhang et al, 2022c ), but also ameliorates hyperuricemic nephropathy via enhancing PINK1-associated mitophagy in renal TECs ( Zhang et al, 2022a ). A study showed that urolithin A treatment restores renal function, and alleviates tubular cell dilation and collagen deposition in glomerular basement membrane ( Zhang et al, 2022a ).…”

Section: Natural Products For Regulating Mitochondrial Functionmentioning

confidence: 99%

Natural products for kidney disease treatment: Focus on targeting mitochondrial dysfunction

2023

View full text Add to dashboard Cite

The patients with kidney diseases are increasing rapidly all over the world. With the rich abundance of mitochondria, kidney is an organ with a high consumption of energy. Hence, renal failure is highly correlated with the breakup of mitochondrial homeostasis. However, the potential drugs targeting mitochondrial dysfunction are still in mystery. The natural products have the superiorities to explore the potential drugs regulating energy metabolism. However, their roles in targeting mitochondrial dysfunction in kidney diseases have not been extensively reviewed. Herein, we reviewed a series of natural products targeting mitochondrial oxidative stress, mitochondrial biogenesis, mitophagy, and mitochondrial dynamics. We found lots of them with great medicinal values in kidney disease. Our review provides a wide prospect for seeking the effective drugs targeting kidney diseases.

show abstract

Urolithin A alleviates acute kidney injury induced by renal ischemia reperfusion through the p62‐Keap1‐Nrf2 signaling pathway

Cited by 21 publications

References 50 publications

Urolithin A Attenuates Hyperuricemic Nephropathy in Fructose-Fed Mice by Impairing STING-NLRP3 Axis-Mediated Inflammatory Response via Restoration of Parkin-Dependent Mitophagy

Urolithin A Attenuates Hyperuricemic Nephropathy in Fructose-Fed Mice by Impairing STING-NLRP3 Axis-Mediated Inflammatory Response via Restoration of Parkin-Dependent Mitophagy

Astragaloside IV protects against ischemia/reperfusion (I/R)-induced kidney injury based on the Keap1-Nrf2/ARE signaling pathway

Natural products for kidney disease treatment: Focus on targeting mitochondrial dysfunction

Contact Info

Product

Resources

About