Honokiol reduces doxorubicin-induced cardiotoxicity in vitro by inhibiting pyroptosis via activating AMPK/Nrf2 signaling.
10.12122/j.issn.1673-4254.2022.08.13
- Author:
Feng Mei XIONG
1
;
Rui Ping LIU
2
;
Yang LI
1
;
Na SUN
3
Author Information
1. Department of Pharmacy, Xi'an Children's Hospital, Xi'an 710003, China.
2. Department of Nutrition, Xi'an Children's Hospital, Xi'an 710003, China.
3. Institute of Basic Medical Science, Xi'an Medical University, Xi'an 710021, China.
- Publication Type:Journal Article
- Keywords:
cardiotoxicity;
doxorubicin;
honokiol;
pyroptosis
- MeSH:
AMP-Activated Protein Kinases/metabolism*;
Allyl Compounds;
Biphenyl Compounds;
Cardiotoxicity/pathology*;
Caspase 3/metabolism*;
Cytochromes c;
Doxorubicin/adverse effects*;
Humans;
Interleukin-6/metabolism*;
Myocytes, Cardiac;
NF-E2-Related Factor 2/metabolism*;
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*;
Phenols;
Pyroptosis;
RNA, Messenger/metabolism*;
Tumor Necrosis Factor-alpha/metabolism*
- From:
Journal of Southern Medical University
2022;42(8):1205-1211
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effect of honokiol (HKL) for reducing doxorubicin (DOX)-induced cardiotoxicity in H9c2 cells and the underlying mechanisms.
METHODS:H9c2 cells were divided into control group, DOX group, HKL + DOX group, and HKL+compound C+DOX group. After 24 h of corresponding treatment, the cells were examined for morphological changes and cell viability using CCK-8 assay. The mRNA expressions of the inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were detected by RT-PCR, and the protein levels of cleaved caspase-3, cytochrome c, NOD-like receptor pyrin domain containing 3 (NLRP3), caspase-1, apoptosis-associated speck-like protein containing a CARD (ASC), p-AMPK and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) were detected with Western blotting; the expressions of NLRP3 and p-AMPK also detected with immunofluorescence staining.
RESULTS:DOX treatment caused swelling and significantly lowered the viability of H9c2 cells (P < 0.05), resulting also in increased mRNA expressions of TNF-α, IL-6 and IL-1β (P < 0.05) and protein expressions of cleaved caspase-3, cytochrome c, NLRP3, caspase-1 and ASC (P < 0.05) but reduced protein levels of p-AMPK and Nrf2 (P < 0.05); fluorescence staining showed significantly increased NLRP3 expression and decreased expression of p-AMPK in DOX-treated cells (P < 0.05). All these changes in COX-treated cells were significantly alleviated by HKL treatment (P < 0.05). The application of compound C obviously mitigated the protective effects of HKL against DOX-induced cardiotoxicity in H9c2 cells.
CONCLUSIONS:HKL can alleviate DOX-induced cardiotoxicity by inhibiting pyroptosis in H9c2 cells, and this effect is mediated by activation of AMPK to regulate Nrf2 signaling.
