Kaixinsan alleviates adriamycin-induced depression-like behaviors in mice by reducing ferroptosis in the prefrontal cortex
10.12122/j.issn.1673-4254.2024.08.02
- VernacularTitle:开心散通过减轻前额叶皮质铁死亡缓解小鼠的阿霉素化疗性抑郁
- Author:
Mingzi OUYANG
1
;
Jiaqi CUI
;
Hui WANG
;
Zheng LIANG
;
Dajin PI
;
Liguo CHEN
;
Qianjun CHEN
;
Yingchao WU
Author Information
1. 暨南大学中医学院,广东 广州 510632
- Keywords:
Kaixinsan;
breast cancer;
chemotherapy;
depression;
ferroptosis
- From:
Journal of Southern Medical University
2024;44(8):1441-1449
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of Kaixinsan(KXS,a traditional Chinese medicine formula)for alleviating adriamycin-induced depression-like behaviors in mice bearing breast cancer xenografts and explore the pharmacological mechanism.Methods Forty female BALB/c mice were randomized equally into control group,model group,and low-and high-dose KXS treatment groups,and in the latter 3 groups,mouse models bearing orthotopic breast cancer 4T1 cell xenografts were established and treated with adriamycin along with saline or KXS via gavage.Depression-like behaviors of the mice were assessed using open field test and elevated plus-maze test,and the changes in serum levels of depression-related factors were examined.RNA-seq analysis and transmission electron microscopy were used and ferroptosis-related factors were detected to explore the mechanisms of adriamycin-induced depression and the therapeutic mechanism of KXS.The results were verified in SH-SY5Y cells using ferroptosis inhibitor Fer-1 as the positive control.Results KXS significantly alleviated depression-like behaviors and depression-related serological changes induced by adriamycin in the mouse models.RNA-seq results suggested that KXS alleviated chemotherapy-induced depression by regulating oxidative stress,lipid metabolism and iron ion binding in the prefrontal cortex.Pathological analysis and detection of ferroptosis-related factors showed that KXS significantly reduced ferroptosis in the prefrontal cortex of adriamycin-treated mice.In SH-SY5Y cells,both KXS-medicated serum and the ferroptosis inhibitor were capable of attenuating adriamycin-induced cell ferroptosis.Conclusion KXS alleviates adriamycin-induced depression-like behaviors in mice by reducing ferroptosis in the prefrontal cortex of breast cancer-bearing mice.
