Honokiol antagonizes doxorubicin‑induced cardiomyocyte senescence by inhibiting TXNIP‑mediated NLRP3 inflammasome activation

Huang,Pian‑Pian; Fu,Jun; Liu,Li‑Hua; Wu,Ke‑Fei; Liu,Hong‑Xia; Qi,Ben‑Ming; Liu,Yun; Qi,Ben‑Ling

doi:10.3892/ijmm.2019.4393

Honokiol antagonizes doxorubicin‑induced cardiomyocyte senescence by inhibiting TXNIP‑mediated NLRP3 inflammasome activation

Authors:
- Pian‑Pian Huang
- Jun Fu
- Li‑Hua Liu
- Ke‑Fei Wu
- Hong‑Xia Liu
- Ben‑Ming Qi
- Yun Liu
- Ben‑Ling Qi
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Affiliations: Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Radiology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Otorhinolaryngology, First People's Hospital of Yunnan Province, Kunming, Yunnan 650000, P.R. China
Published online on: November 1, 2019 https://doi.org/10.3892/ijmm.2019.4393
Pages: 186-194
Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Senescence of cardiomyocytes is considered a key factor for the occurrence of doxorubicin (Dox)‑associated cardiomyopathy. The NOD‑like receptor family pyrin domain‑containing 3 (NLRP3) inflammasome is reported to be involved in the process of cellular senescence. Furthermore, thioredoxin‑interactive protein (TXNIP) is required for NLRP3 inflammasome activation and is considered to be a key component in the regulation of the pathogenesis of senescence. Studies have demonstrated that pretreatment with honokiol (Hnk) can alleviate Dox‑induced cardiotoxicity. However, the impact of Hnk on cardiomyocyte senescence elicited by Dox and the underlying mechanisms remain unclear. The present study demonstrated that Hnk was able to prevent Dox‑induced senescence of H9c2 cardiomyocytes, indicated by decreased senescence‑associated β‑galactosidase (SA‑β‑gal) staining, as well as decreased expression of p16INK4A and p21. Hnk also inhibited TXNIP expression and NLRP3 inflammasome activation in Dox‑stimulated H9c2 cardiomyocytes. When TXNIP expression was enforced by adenovirus‑mediated gene overexpression, the NLRP3 inflammasome was activated, which led to inhibition of the anti‑inflammation and anti‑senescence effects of Hnk on H9c2 cardiomyocytes under Dox treatment. Furthermore, adenovirus‑mediated TXNIP‑silencing inhibited the NLRP3 inflammasome. Consistently, TXNIP knockdown enhanced the anti‑inflammation and anti‑senescence effects of Hnk on H9c2 cardiomyocytes under Dox stimulation. In summary, Hnk was found to be effective in protecting cardiomyocytes against Dox‑stimulated senescence. This protective effect was mediated via the inhibition of TXNIP expression and the subsequent suppression of the NLRP3 inflammasome. These results demonstrated that Hnk may be of value as a cardioprotective drug by inhibiting cardiomyocyte senescence.

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