Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

Fisetin attenuates tunicamycin-induced endoplasmic reticulum stress and apoptosis in cardiomyocytes via Nrf2-associated anti-oxidant responses

Articles in Press

Document Type : Original Article

Authors
Hui Chen 1
Mengze Du 1
Tianyu Chen 2
Chunmei Luo 1
Li Cai 1
Lin Ning 3
Changhan Ouyang 4
1 School of Healthcare Technology, Chengdu Neusoft University, Chengdu, Sichuan Province, P.R. China
2 School of Pharmacy, Chengdu Medical College, Chengdu, Sichuan Province, P.R. China
3 School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China
4 School of Pharmacy, Hubei University of Science and Technology, Xianning, Hubei Province, P.R. China
10.22038/ijbms.2026.97010.20860
Abstract
Objective(s): Fisetin, a natural flavonoid, has anti-oxidant and anti-apoptotic properties; however, its effect on endoplasmic reticulum stress (ERS)-induced cardiomyocyte injury remains unclear. This study aimed to investigate fisetin’s protective effect against tunicamycin-induced ERS injury in H9c2 cardiomyocytes and the role of the Nrf2-associated signaling pathway.
Materials and Methods: An ERS model was established in H9c2 cardiomyocytes using tunicamycin. Cell viability, reactive oxygen species (ROS) levels, apoptotic rate, and expression of ERS-related proteins were assessed by CCK-8 assay, DCFH-DA probe, flow cytometry, and Western blotting, respectively. The role of the Nrf2-associated signaling pathway was further investigated using the Nrf2-specific inhibitor ML-385.
Results: Fisetin pretreatment dose-dependently increased the viability of tunicamycin-injured H9c2 cells, reduced intracellular ROS levels, decreased the apoptosis rate, down-regulated GRP78 and CHOP protein expression, and up-regulated Nrf2 and its downstream anti-oxidant proteins HO-1, NQO-1, and catalase. Notably, co-treatment with ML-385 significantly reversed the above protective effects of fisetin.
Conclusion: Fisetin attenuates tunicamycin-induced ERS-mediated cardiomyocyte injury, and the underlying mechanism involves an Nrf2-associated anti-oxidant response. ML-385 reversed this protective effect, supporting a role for Nrf2-related anti-oxidant responses in suppressing oxidative stress and apoptosis.
Keywords
Cardiomyocytes
Endoplasmic reticulum- stress
Fisetin
Tunicamycin
Nrf2
Subjects
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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 15 November 2026