Exploring the pathophysiological influence of heme oxygenase-1 on neuroinflammation and depression: A study of phytotherapeutic-based modulation

Phytomedicine. 2024 May:127:155466. doi: 10.1016/j.phymed.2024.155466. Epub 2024 Feb 19.


Background: The heme oxygenase (HO) system plays a significant role in neuroprotection and reduction of neuroinflammation and neurodegeneration. The system, via isoforms HO-1 and HO-2, regulates cellular redox balance. HO-1, an antioxidant defense enzyme, is highlighted due to its association with depression, characterized by heightened neuroinflammation and impaired oxidative stress responses.

Methodology: We observed the pathophysiology of HO-1 and phytochemicals as its modulator. We explored Science Direct, Scopus, and PubMed for a comprehensive literature review. Bibliometric and temporal trend analysis were done using VOSviewer.

Results: Several phytochemicals can potentially alleviate neuroinflammation and oxidative stress-induced depressive symptoms. These effects result from inhibiting the MAPK and NK-κB pathways - both implicated in the overproduction of pro-inflammatory factors - and from the upregulation of HO-1 expression mediated by Nrf2. Bibliometric and temporal trend analysis further validates these associations.

Conclusion: In summary, our findings suggest that antidepressant agents can mitigate neuroinflammation and depressive disorder pathogenesis via the upregulation of HO-1 expression. These agents suppress pro-inflammatory mediators and depressive-like symptoms, demonstrating that HO-1 plays a significant role in the neuroinflammatory process and the development of depression.

Keywords: Depression; Heme oxygenase; Neuroinflammation; Oxidative stress; Phytochemicals; Psychiatric disorder.

Publication types

  • Review

MeSH terms

  • Antioxidants / pharmacology
  • Depression / drug therapy
  • Heme Oxygenase (Decyclizing) / metabolism
  • Heme Oxygenase-1* / metabolism
  • Humans
  • NF-E2-Related Factor 2 / metabolism
  • Neuroinflammatory Diseases*
  • Oxidative Stress


  • Heme Oxygenase-1
  • Heme Oxygenase (Decyclizing)
  • Antioxidants
  • NF-E2-Related Factor 2