4-Hydroxycinnamic acid attenuates neuronal cell death by inducing expression of plasma membrane redox enzymes and improving mitochondrial functions

Sujin Park, Yoon A. Kim, Jaewang Lee, Hyunsoo Seo, Sang Jip Nam, Dong Gyu Jo, Dong Hoon Hyun

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Many approaches to neurodegenerative diseases that focus on amyloid-β clearance and gene therapy have not been successful. Some therapeutic applications focus on enhancing neuronal cell survival during the pathogenesis of neurodegenerative diseases, including mitochondrial dysfunction. Plasma membrane (PM) redox enzymes are crucial in maintaining cellular physiology and redox homeostasis in response to mitochondrial dysfunction. Neurohormetic phytochemicals are known to induce the expression of detoxifying enzymes under stress conditions. In this study, mechanisms of neuroprotective effects of 4-hydroxycinnamic acid (HCA) were examined by analyzing cell survival, levels of abnormal proteins, and mitochondrial functions in two different neuronal cells. HCA protected two neuronal cells exhibited high expression of PM redox enzymes and the consequent increase in the NAD+/NADH ratio. Cells cultured with HCA showed delayed apoptosis and decreased oxidative/nitrative damage accompanied by decreased ROS production in the mitochondria. HCA increased the mitochondrial complexes I and II activities and ATP production. Also, HCA increased mitochondrial fusion and decreased mitochondrial fission. Overall, HCA maintains redox homeostasis and energy metabolism under oxidative/metabolic stress conditions. These findings suggest that HCA could be a promising therapeutic approach for neurodegenerative diseases.

Original languageEnglish
Pages (from-to)1287-1299
Number of pages13
JournalFood Science and Human Wellness
Issue number4
StatePublished - Jul 2023

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) of the Korean Government (NRF-2021R1F1A1051212), and by Logsynk Co. Ltd. (2-2021-1435-001).

Publisher Copyright:
© 2022


  • 4-Hydroxycinnamic acid
  • Cytochrome b5 reductase
  • Improved mitochondrial functions
  • NADH-quinone oxidoreductase 1 (NQO1)
  • Neuroprotection


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