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Salvianolic Acid A Protects the Kidney against Oxidative Stress by Activating the AktGSK-3βNrf2 Signaling Pathway and Inhibiting the NF-κB Signaling Pathway in 56 Nephrectomized Rats
Joint Authors
Wang, Jiahong
Zhang, Zhou
Zhang, Hong-feng
Wang, Yan-li
Gao, Cheng
Gu, Yan-ting
Huang, Jian
Wang, Jin-hui
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-16, 16 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-03-18
Country of Publication
Egypt
No. of Pages
16
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Zhang, Hong-feng& Wang, Jiahong& Wang, Yan-li& Gao, Cheng& Gu, Yan-ting& Huang, Jian…[et al.]. 2019. Salvianolic Acid A Protects the Kidney against Oxidative Stress by Activating the AktGSK-3βNrf2 Signaling Pathway and Inhibiting the NF-κB Signaling Pathway in 56 Nephrectomized Rats. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-16.
https://search.emarefa.net/detail/BIM-1202965
Modern Language Association (MLA)
Zhang, Hong-feng…[et al.]. Salvianolic Acid A Protects the Kidney against Oxidative Stress by Activating the AktGSK-3βNrf2 Signaling Pathway and Inhibiting the NF-κB Signaling Pathway in 56 Nephrectomized Rats. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-16.
https://search.emarefa.net/detail/BIM-1202965
American Medical Association (AMA)
Zhang, Hong-feng& Wang, Jiahong& Wang, Yan-li& Gao, Cheng& Gu, Yan-ting& Huang, Jian…[et al.]. Salvianolic Acid A Protects the Kidney against Oxidative Stress by Activating the AktGSK-3βNrf2 Signaling Pathway and Inhibiting the NF-κB Signaling Pathway in 56 Nephrectomized Rats. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-16.
https://search.emarefa.net/detail/BIM-1202965
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1202965