Shenshuaifu Granule Attenuates Acute Kidney Injury by Inhibiting Ferroptosis Mediated by p53/SLC7A11/GPX4 Pathway

• Published in: Drug design, development and therapy development and therapy, 2023-11, Vol.17, p.3363-3383
• Main Authors: Jin, Xiaoming, He, Riming, Lin, Yunxin, Liu, Jiahui, Wang, Yuzhi, Li, Zhongtang, Liao, Yijiao, Yang, Shudong
• Format: Article
• Language: English
• Subjects: acute kidney injury; Cell death; cisplatin; Ferritin; ferroptosis; High performance liquid chromatography; Inflammation; p53/slc7a11/gpx4 pathway; shenshuaifu granule; Superoxide; Tumor proteins; Urea
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S433994

Background: Acute kidney injury (AKI) is a common clinical condition resulting in a rapid decline in renal function, and requires improvement in effective preventive measures. Ferroptosis, a novel form of cell death, is closely related to AKI. Shenshuaifu granule (SSF) has been demonstrated to prevent AKI through suppressing inflammation and apoptosis. Objective: This study aimed to explore whether SSF can inhibit ferroptosis in AKI. Methods: Active ingredients in SSF were detected through HPLC-MS/MS, and their binding abilities with ferroptosis were evaluated by molecular docking. Then, male C57/BL/6J mice were randomly divided into control, cisplatin, and cisplatin+SSF groups. In the latter two groups, mice were intraperitoneally injected with 20 mg/kg of cisplatin. For five consecutive days prior to cisplatin injection, mice in the cisplatin+SSF group were gavaged with 5.2 g/kg of SSF per day. 72 h after cisplatin injection, the mice were sacrificed. Serum creatinine (SCr) and blood urea nitrogen (BUN) were measured to evaluate renal function. H&E and FAS staining were used to observe pathological damage of kidney. Cell death was observed by TUNEL staining, and iron accumulation in kidneys of mice was detected by Prussian blue staining. Western blotting, immunohis-tochemistry, and immunofluorescence were used to investigate the presence of inflammation, oxidative stress, mitochondrial dysfunction, iron deposition, and lipid peroxidation in mouse kidneys. Results: Active ingredients in SSF had strong affinities with ferroptosis. SSF reduced SCr (p