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Nicotiflorin attenuates cell apoptosis in renal ischemia-reperfusion injury through activating transcription factor 3
Lin Wang1, Chenyu Li1,2, Chen Guan1
1Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Introduction:
Nicotiflorin is the main characteristic component of Nymphaea candida, which is a natural product that reportedly ameliorates acute injury of the liver and cerebral cortex, but the effect of nicotiflorin on acute kidney injury (AKI) remains unknown. This study aimed to investigate the effects of nicotiflorin on ischaemia/reperfusion (I/R) AKI and the associated mechanisms.
Methods:
We performed both (a) in vivo experiments with C57BL/6 mice with bilateral renal pedicles clamped for 45 minutes and (b) in vitro experiments with human kidney epithelial cells (HK-2) exposed to hypoxia/reoxygenation to mimic I/R injury to study the role of nicotiflorin in AKI.
Results:
In vivo, nicotiflorin administration exerted protective effects on renal injury, as demonstrated by reductions in the levels of caspase3 and Bad (P < .05), the upregulation of Bcl-2 expression (P < .05) and improved renal histologic changes, which suggested that nicotiflorin can alleviate I/R injury and cell apoptosis. In vitro, nicotiflorin at a concentration of 75 μg/mL protected cells from hypoxia, which further confirmed that nicotiflorin exerts beneficial effects on hypoxia/reoxygenation. Through computational molecular docking, we found that activating transcription factor 3 (ATF3) exhibits a robust interaction with nicotiflorin with a simulated binding energy of -9.2°. We verified the interaction of nicotiflorin with ATF3 in HK-2 cells, and found that nicotiflorin reduced the apoptosis of HK-2 through ATF3.
Conclusion:
Based on the above-described results, nicotiflorin appears to have a beneficial impact on deteriorated renal function, as demonstrated using an experimental I/R model. The underlying mechanisms of nicotiflorin might inhibit HK-2 cell apoptosis through ATF3.
Insights
Nicotiflorin, a natural compound, protects against kidney injury by reducing cell death. It works by inhibiting apoptosis through interaction with activating transcription factor 3 (ATF3).
Area of Science:
- Pharmacology
- Nephrology
- Biochemistry
Background:
- Nicotiflorin, derived from Nymphaea candida, is known for liver and cerebral cortex protection.
- Its effects on acute kidney injury (AKI) were previously unknown.
- This study investigates nicotiflorin's potential in treating ischaemia/reperfusion (I/R) induced AKI.
Purpose of the Study:
- To evaluate the protective effects of nicotiflorin against I/R-induced AKI.
- To elucidate the underlying molecular mechanisms of nicotiflorin's action in AKI.
Main Methods:
- In vivo studies using C57BL/6 mice subjected to renal pedicle clamping.
- In vitro experiments with human kidney epithelial cells (HK-2) under hypoxia/reoxygenation.
- Computational molecular docking to identify potential protein interactions.
Main Results:
- Nicotiflorin administration improved renal histology and reduced apoptosis markers (caspase3, Bad) while upregulating Bcl-2 in vivo.
- Nicotiflorin protected HK-2 cells against hypoxia/reoxygenation in vitro.
- Molecular docking revealed a strong interaction between nicotiflorin and activating transcription factor 3 (ATF3), which was confirmed in cells, showing nicotiflorin reduces HK-2 cell apoptosis via ATF3.
Conclusions:
- Nicotiflorin demonstrates a protective effect on renal function in an experimental I/R AKI model.
- The mechanism involves the inhibition of HK-2 cell apoptosis mediated by ATF3.
