Study on the effect and mechanism of magnolol derivative on cisplatin-induced acute kidney injury
10.19405/j.cnki.issn1000–1492.2026.06.016
- VernacularTitle:厚朴酚酯衍生物对顺铂诱导的急性肾损伤的作用及其初步机制研究
- Author:
Rui SHI
1
;
Haochen XU
1
;
Jie PENG
1
;
Wanghui LIN
1
;
Xulei WANG
2
;
Wei WEI
1
;
Chun WANG
1
;
Bingfa XU
1
Author Information
1. School of Pharmaceutical Sciences， Anhui Medical University，Hefei 230032
2. Laboratory Animal Center， Anhui Medical University， Hefei 230032
- Publication Type:Journal Article
- Keywords:
magnolol ester derivative;
cisplatin;
acute kidney injury;
cellular senescence;
KAT7;
p21
- From:
Acta Universitatis Medicinalis Anhui
2026;61(6):1103-1110
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the protective effect of magnolol ester derivative YW against cisplatin （Cis）-induced acute kidney injury （AKI） and to explore its effect and preliminary mechanisms on Cis-induced AKI. MethodsThe research group designed and synthesized the magnolol ester derivative YW using magnolol as the parent core. Molecular docking was employed to predict the binding interaction between YW and lysine acetyltransferase 7 （KAT7）. A Cis-induced AKI model was established in C57BL/6J mice. Mice were divided into the normal control group， model group， YW low/medium/high dose groups （17.5， 35， 70 mg/kg）， and the positive control amifostine group. Renal function was assessed by measuring serum creatinine （Scr） and blood urea nitrogen （BUN） levels. Pathological changes were evaluated via HE staining and scoring of kidney tissues. Protein expression levels of kidney injury molecule 1 （KIM-1）， lysine acetyltransferase 7 （KAT7）， and cyclin-dependent kinase inhibitor 1A （p21） in kidney tissues were detected by Western blot （WB）. HK-2 cells were treated with different concentrations of YW； cell viability was measured by CCK-8 assay. WB was used to detect the expression levels of the renal injury marker KIM-1， KAT7， and its downstream protein p21. Cellular senescence was assessed by senescence-associated β-galactosidase （SA-β-Gal） staining. ResultsYW could stably bind to KAT7. In vivo experiments showed that， compared with the model group， all YW dose groups， especially the medium and high doses， significantly reduced the elevated levels of Scr and BUN in AKI mice （P<0.001） and effectively ameliorated renal histopathological damage. YW significantly downregulated the protein expression levels of KIM-1， KAT7， and p21 in kidney tissues （P<0.05）. Concentrations of YW≤10 μmol/L had no significant effect on HK-2 cell viability. YW inhibited the Cis-induced decline in HK-2 cell viability （P<0.05）， suppressed the Cis-induced upregulation of KIM-1， KAT7， and p21 proteins （P<0.05）， and significantly decreased the percentage of SA-β-Gal-positive cells （P<0.01）. ConclusionYW suppresses the expression of KAT7 and p21 proteins and inhibits the decline in HK-2 cell viability in cisplatin-induced AKI， significantly mitigates HK-2 cell senescence， and improves renal function， providing preliminary experimental evidence for developing AKI treatment strategies based on structural optimization of natural products.
