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Cordycepin inhibits kidney injury by regulating GSK-3β-mediated Nrf2 activation
Zhiling Tang1, Kean Chen1, Chun Sun1
1Department of Urology Surgery, The Second Affiliated Hospital of Jiaxing University, Zhejiang, China.
Abstract:
We explored the role and mechanism of cordycepin (COR) in inhibiting kidney injury. A mouse model of kidney injury was established using cisplatin (CDDP), and the kidney function, histopathology, and ferroptosis indices in mice were detected after intervening with COR. The targets of COR-ferroptosis-kidney injury were analyzed by network pharmacology, based on which the association between glycogen synthase kinase-3 beta (GSK-3β) and COR was determined. HK-2 cells were cultured in vitro and treated separately with ferroptosis inducers erastin and CDDP. After the COR intervention, the level of ferroptosis was monitored. In vitro experiments found that COR could inhibit ferroptosis and CDDP-induced kidney injury. Network pharmacological analysis revealed that GSK-3β was the target of COR. After inhibiting GSK-3β expression, COR could not further inhibit the occurrence of ferroptosis. In vitro results also indicated that COR could inhibit ferroptosis in HK-2 cells. According to our findings, COR can ameliorate CDDP-induced kidney injury through GSK-3β-mediated ferroptosis signaling. We identify new pharmacological effect and target for COR, the major component of Cordyceps sinensis.
Insights
Cordycepin (COR) protects against cisplatin-induced kidney injury by inhibiting ferroptosis. This effect is mediated through glycogen synthase kinase-3 beta (GSK-3β), revealing a new therapeutic target for kidney damage.
Area of Science:
- Pharmacology
- Nephrology
- Biochemistry
Background:
- Kidney injury is a significant clinical challenge.
- Cisplatin (CDDP) is a common chemotherapeutic agent that causes kidney damage.
- Ferroptosis, a form of regulated cell death, plays a role in kidney injury.
Purpose of the Study:
- To investigate the protective role of cordycepin (COR) against kidney injury.
- To elucidate the mechanism underlying COR's protective effects, focusing on ferroptosis.
- To identify the molecular targets of COR in kidney injury.
Main Methods:
- A mouse model of cisplatin-induced kidney injury was established.
- Kidney function, histopathology, and ferroptosis markers were assessed.
- Network pharmacology was used to predict COR targets.
- In vitro studies using HK-2 cells were performed to validate findings.
Main Results:
- Cordycepin (COR) administration ameliorated cisplatin (CDDP)-induced kidney injury in mice.
- COR inhibited ferroptosis in both in vivo and in vitro models.
- Network pharmacology identified glycogen synthase kinase-3 beta (GSK-3β) as a key target of COR.
- Inhibition of GSK-3β abolished the ferroptosis-inhibitory effect of COR.
Conclusions:
- Cordycepin (COR) exerts protective effects against CDDP-induced kidney injury.
- The mechanism involves the inhibition of ferroptosis via GSK-3β signaling.
- GSK-3β is a novel therapeutic target for COR in kidney injury treatment.
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