Saikosaponin a attenuates lead-induced kidney injury through activating Nrf2 signaling pathway

2021 ◽  
Vol 242 ◽  
pp. 108945
Author(s):  
Yanyan Song ◽  
Haowen Sun ◽  
Siyuan Gao ◽  
Ke Tang ◽  
Yao Zhao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Kidney Injury ◽  
Nrf2 Signaling Pathway ◽  
Saikosaponin A

scholarly journals Salvianolic Acid A Protects the Kidney against Oxidative Stress by Activating the Akt/GSK-3β/Nrf2 Signaling Pathway and Inhibiting the NF-κB Signaling Pathway in 5/6 Nephrectomized Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Hong-feng Zhang ◽  
Jia-hong Wang ◽  
Yan-li Wang ◽  
Cheng Gao ◽  
Yan-ting Gu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Western Blot ◽  
Signaling Pathway ◽  
Kidney Injury ◽  
Dependent Manner ◽  
Salvianolic Acid ◽  
Nrf2 Signaling Pathway ◽  
Antioxidative Effects ◽  
Dose Dependent

Salvianolic acid A (SAA) is a bioactive polyphenol extracted from Salviae miltiorrhizae Bunge, which possesses a variety of pharmacological activities. In our previous study, we have demonstrated that SAA effectively attenuates kidney injury and inflammation in an established animal model of 5/6 nephrectomized (5/6Nx) rats. However, there has been limited research regarding the antioxidative effects of SAA on chronic kidney disease (CKD). Here, we examined the antioxidative effects and underlying mechanisms of SAA in 5/6Nx rats. The rats were injected with SAA (2.5, 5, and 10 mg·kg-1·d-1, ip) for 28 days. Biochemical, flow cytometry, and Western blot analyses showed that SAA significantly increased the activities of total superoxide dismutase (T-SOD), glutathione peroxidase (GPx), and catalase (CAT) and lowered the levels of malondialdehyde (MDA), reactive oxygen species (ROS), and NADPH oxidase 4 (NOX-4) in a dose-dependent manner in 5/6Nx rats and in H2O2-induced HK-2 cells in vitro. Moreover, SAA enhanced the activation of the protein kinase B/glycogen synthase kinase-3β/nuclear factor-erythroid-2-related factor 2 (Akt/GSK-3β/Nrf2) signaling pathway in a dose-dependent manner and subsequently increased the expression of heme oxygenase-1 (HO-1) in the kidney of 5/6Nx rats, which were consistent with those obtained in H2O2-induced HK-2 cells in vitro shown by Western blot analysis. Furthermore, SAA significantly increased the expression of intranuclear Nrf2 and HO-1 proteins compared to HK-2 cells stimulated by LPS on the one hand, which can be enhanced by QNZ to some extent; on the other hand, SAA significantly lowered the expression of p-NF-κB p65 and ICAM-1 proteins compared to HK-2 cells stimulated by H2O2, which can be abrogated by ML385 to some extent. In conclusion, our results demonstrated that SAA effectively protects the kidney against oxidative stress in 5/6Nx rats. One of the pivotal mechanisms for the protective effects of SAA on kidney injury was mainly related with its antioxidative roles by activating the Akt/GSK-3β/Nrf2 signaling pathway and inhibiting the NF-κB signaling pathway.

scholarly journals Protective Effect of Tempol on Acute Kidney Injury Through PI3K/Akt/Nrf2 Signaling Pathway

2016 ◽  
Vol 41 (2) ◽  
pp. 129-138 ◽  
Author(s):  
Gensheng Zhang ◽  
Qiaoling Wang ◽  
Qin Zhou ◽  
Renjun Wang ◽  
Minze Xu ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Protective Effect ◽  
Signaling Pathway ◽  
Kidney Injury ◽  
Nrf2 Signaling Pathway

Saikosaponin A Inhibits LPS-Induced Endometritis in Mice Through Activating Nrf2 Signaling Pathway

Inflammation ◽  
2018 ◽  
Vol 41 (4) ◽  
pp. 1508-1514 ◽  
Author(s):  
Jing Wang ◽  
Weiwei Wang ◽  
Yongtao Pang
Keyword(s):  
Signaling Pathway ◽  
Nrf2 Signaling Pathway ◽  
Saikosaponin A

Involvement of Nrf2 and mitochondrial apoptotic signaling in trehalose protection against cadmium-induced kidney injury

Metallomics ◽  
2020 ◽  
Author(s):  
Rui-Feng Fan ◽  
Zi-Fa Li ◽  
Dong Zhang ◽  
Zhen-Yong Wang
Keyword(s):  
Protective Effect ◽  
Signaling Pathway ◽  
Kidney Injury ◽  
Apoptotic Signaling ◽  
Nrf2 Signaling Pathway

Trehalose exerted its renal protective effect via inhibiting cadmium-activated Nrf2 signaling pathway, which was closely related with mitochondrial apoptotic signaling pathway.

scholarly journals Leonurine alleviates ferroptosis in cisplatin-induced acute kidney injury by activating the Nrf2 signaling pathway

2021 ◽  
Author(s):  
Jianqiang HU ◽  
Wenjing Gu ◽  
Ning Ma ◽  
Xiaoye Fan ◽  
Xinxin Ci
Keyword(s):  
Lipid Peroxidation ◽  
Acute Kidney Injury ◽  
Signaling Pathway ◽  
Lipid Peroxide ◽  
Kidney Injury ◽  
Iron Accumulation ◽  
Protective Effects ◽  
Nrf2 Signaling Pathway

Background and purpose: Increasing evidence suggests that ferroptosis plays a key role in the pathophysiology of acute kidney injury induced by cisplatin. The Nrf2 signaling pathway regulates oxidative stress and lipid peroxidation and positively regulates cisplatin-induced AKI (CI-AKI). However, Nrf2 and its activator leonurine on ferroptosis after CI-AKI remain unclear. Experimental Approach: The anti-ferroptotic effects of Nrf2 and its activator leonurine were assessed using a mouse model of cisplatin-induced AKI. In vitro, the potential effects of leonurine on erastin- and RSL3-induced HK-2 human PTEC ferroptosis were examined. Key Results: As expected, Nrf2 deletion induced ferroptosis-related protein expression and iron accumulation in vivo, further aggravating CI-AKI. The Nrf2 activator leonurine prevented iron accumulation and lipid peroxidation and inhibited ferroptosis in vitro, while these effects were abolished in siNrf2-treated cells. Moreover, leonurine potently ameliorated cisplatin-induced renal damage, as indicated by the assessment of SCr, BUN, KIM-1, and NGAL. Importantly, leonurine activated the Nrf2 antioxidative signaling pathway and prohibited changes in ferroptosis-related morphological and biochemical indicators, such as the MDA level, SOD and GSH depletion and GPX4 and xCT downregulation, in CI-AKI. Moreover, Nrf2 KO mice were more susceptible to ferroptosis after CI-AKI than control mice, and the protective effects of leonurine on AKI and ferroptosis were largely abolished in Nrf2 KO mice. Conclusion and Implications: These data suggest that the renal protective effects of Nrf2 and its activator leonurine on CI-AKI are achieved at least partially by inhibiting lipid peroxide-mediated ferroptosis and highlight the potential of leonurine as a CI-AKI treatment.

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