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Journal of Integrative Medicine ›› 2023, Vol. 21 ›› Issue (5): 464-473.doi: 10.1016/j.joim.2023.08.002

• Original Experimental Research • Previous Articles     Next Articles

Sulforaphane, an NRF2 agonist, alleviates ferroptosis in acute liver failure by regulating HDAC6 activity

Yan-qiong Zhang, Chun-xia Shi, Dan-mei Zhang, Lu-yi Zhang, Lu-wen Wang, Zuo-jiong Gong   

  1. Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
  • Received:2022-11-13 Accepted:2023-06-01 Online:2023-09-20 Published:2023-08-21
  • Contact: Zuo-jiong Gong


Acute liver failure (ALF) is characterized by severe liver dysfunction, rapid progression and high mortality and is difficult to treat. Studies have found that sulforaphane (SFN), a nuclear factor E2-related factor 2 (NRF2) agonist, has anti-inflammatory, antioxidant and anticancer effects, and has certain protective effects on neurodegenerative diseases, cancer and liver fibrosis. This paper aimed to explore the protective effect of SFN in ALF and it possible mechanisms of action.


Lipopolysaccharide and D-galactosamine were used to induce liver injury in vitro and in vivo. NRF2 agonist SFN and histone deacetylase 6 (HDAC6) inhibitor ACY1215 were used to observe the protective effect and possible mechanisms of SFN in ALF, respectively. Cell viability, lactate dehydrogenase (LDH), Fe2+, glutathione (GSH) and malondialdehyde (MDA) were detected. The expression of HDAC6, NRF2, glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4) and solute carrier family 7 member 11 (SLC7A11) were detected by Western blotting and immunofluorescence.


Our results show that NRF2 was activated by SFN. LDH, Fe2+, MDA and ACSL4 were downregulated, while GSH, GPX4 and SLC7A11 were upregulated by SFN in vitro and in vivo, indicating the inhibitory effect of SFN on ferroptosis. Additionally, HDAC6 expression was decreased in the SFN group, indicating that SFN could downregulate the expression of HDAC6 in ALF. After using the HDAC6 inhibitor, ACY1215, SFN further reduced HDAC6 expression and inhibited ferroptosis, indicating that SFN may inhibit ferroptosis by regulating HDAC6 activity.


SFN has a protective effect on ALF, and the mechanism may include reduction of ferroptosis through the regulation of HDAC6.

Key words: Acute liver failure, Sulforaphane, NRF2, HDAC6, Ferroptosis

[1] Bin Lan, Jin-wen Ge, Shao-wu Cheng, Xi-long Zheng, Jun Liao, Chao He, Zheng-qing Rao, Guo-zuo Wang. Extract of Naotaifang, a compound Chinese herbal medicine, protects neuron ferroptosis induced by acute cerebral ischemia in rats. Journal of Integrative Medicine, 2020, 18(4): 344-350.
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