Kaixin San ameliorating doxorubicin-induced neurotoxicity by activating AMPK signaling pathway.
10.19540/j.cnki.cjcmm.20240712.708
- Author:
Ying-Chao WU
1
;
Jia-Qi CUI
2
;
Hui WANG
2
;
Da-Jin PI
2
;
Li-Guo CHEN
2
;
Ming-Zi OUYANG
2
;
Qian-Jun CHEN
3
Author Information
1. State Key Laboratory of Traditional Chinese Medicine Syndrome, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou 510120, China School of Traditional Chinese Medicine, Jinan University Guangzhou 510632, China the Second Clinical Medical College, Guangzhou University of Chinese Medicine Guangzhou 510405, China.
2. School of Traditional Chinese Medicine, Jinan University Guangzhou 510632, China.
3. State Key Laboratory of Traditional Chinese Medicine Syndrome, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou 510120, China.
- Publication Type:Journal Article
- Keywords:
AMPK signaling pathway;
Kaixin San;
doxorubicin;
ferroptosis;
immune response;
neurotoxicity
- MeSH:
Animals;
Doxorubicin/toxicity*;
Mice;
AMP-Activated Protein Kinases/genetics*;
Signal Transduction/drug effects*;
Mice, Inbred BALB C;
Drugs, Chinese Herbal/administration & dosage*;
Female;
Humans;
Cell Line, Tumor;
Neurotoxicity Syndromes/genetics*
- From:
China Journal of Chinese Materia Medica
2024;49(24):6763-6772
- CountryChina
- Language:Chinese
-
Abstract:
The study explored the pathological mechanism of doxorubicin chemotherapy-induced neurotoxicity and the intervention methods of traditional Chinese medicine. BALB/c mice were selected to establish tumor-bearing mouse models by orthotopic injection of 4T1 triple-negative breast cancer cells. After randomization, the mice were treated with doxorubicin chemotherapy or doxorubicin chemotherapy + Kaixin San(KXS). The lesions in the prefrontal cortex of mice were observed by pathological examination, and the lesion information was obtained by long non-coding RNA sequencing. The occurrence of lesions was determined by Western blot and biochemical indicators. In addition, neuroblastoma cells and microglia cells were used to construct in vitro models, and drug-containing serum and p-AMPK dephosphorylation inhibitors were used to further verify the accuracy of animal experiments. Pathological results showed that KXS could alleviate doxorubicin-induced neuronal degeneration in the prefrontal cortex. The long non-coding RNA sequencing suggested that neuronal degeneration and the intervention process of KXS were related to ferroptosis, immune diseases, AMPK signaling pathway, etc. Western blot and biochemical indicators confirmed that this process was directly related to the activation of the AMPK/HIF-1α/ACSL4 signaling pathway to alleviate ferroptosis of neurons and immune response of glial cells. In conclusion, KXS could alleviate doxorubicin-induced neurotoxicity by activating the AMPK signaling pathway and reducing the ferroptosis of neurons and immune response of glial cells.
