Wogonin Reduces Liver Damage from Acetaminophen by Blocking Key Cell Signals

Greg Howard
20th May, 2024

Wogonin Reduces Liver Damage from Acetaminophen by Blocking Key Cell Signals

Image Source: Natural Science News, 2024

Key Findings

  • Researchers from Guangzhou University of Chinese Medicine found that Wogonin, a compound in Chinese skullcap, reduces liver damage caused by acetaminophen in mice
  • Wogonin works by lowering oxidative stress and inflammation in the liver, primarily through the PI3K/AKT signaling pathway
  • The study suggests Wogonin's potential for treating drug-induced liver injuries by targeting specific cellular pathways
Scutellaria baicalensis Georgi (SBG), commonly known as Chinese skullcap, has long been used in traditional Chinese medicine for its anti-inflammatory and antioxidant properties. Recent research from Guangzhou University of Chinese Medicine has focused on Wogonin, a key bioactive compound in SBG, to explore its therapeutic effects on acetaminophen (APAP)-induced liver injury (AILI)[1]. AILI is a prevalent form of drug-induced liver damage, primarily driven by inflammatory responses and oxidative stress. The study aimed to investigate how Wogonin affects AILI and the mechanisms behind its therapeutic action. Researchers pre-treated C57BL/6J mice with varying doses of Wogonin for three days before administering APAP. They collected serum and liver tissue samples 24 hours post-APAP treatment. Additionally, bone marrow-derived macrophages and RAW264.7 cells were cultured and pre-treated with Wogonin before being stimulated with lipopolysaccharide (LPS) to induce an inflammatory response. The results were promising. Wogonin pre-treatment dose-dependently alleviated AILI in mice. This was evidenced by reduced oxidative stress and inflammatory responses in the liver. Liver transcriptome analysis revealed that Wogonin primarily regulates immune function and cytokines in AILI. Further investigation showed that Wogonin suppressed inflammatory responses in macrophages by inhibiting the PI3K/AKT signaling pathway. The therapeutic effects of Wogonin on AILI were consistent in both mice and cell models through the same pathway. This study ties well with previous research on the KEAP1-NRF2 pathway, which is a critical intracellular defense mechanism against oxidative stress. Under normal conditions, KEAP1 targets NRF2 for degradation. However, in response to stress, NRF2 escapes degradation, accumulates in the cell, and translocates to the nucleus to promote an antioxidant response[2]. The ability of Wogonin to suppress oxidative stress in AILI may be linked to its influence on similar cellular pathways, although this specific mechanism was not directly examined in the study. Moreover, the study's findings align with earlier research on Wogonin's therapeutic potential against various cancers, where it was shown to regulate multiple cell signaling pathways[3]. The ability of Wogonin to modulate the PI3K/AKT signaling pathway in AILI further underscores its broad therapeutic potential. The study also sheds light on drug-induced liver injury (DILI), a significant but rare adverse event that can range from mild liver enzyme elevations to severe liver failure[4]. Understanding the mechanisms by which Wogonin alleviates AILI provides valuable insights into developing new therapeutic strategies for managing DILI. The PI3K/AKT pathway, which plays a role in cell survival, growth, and metabolism, emerges as a potential target for therapeutic intervention. In summary, the study from Guangzhou University of Chinese Medicine demonstrates that Wogonin effectively alleviates APAP-induced liver injury in mice by modulating the PI3K/AKT signaling pathway. This research not only expands our understanding of Wogonin's therapeutic potential but also highlights the importance of exploring traditional medicinal compounds for new drug development.

MedicineHealthBiochem

References

Main Study

1) Wogonin Mitigates Acetaminophen-Induced Liver Injury in Mice through Inhibition of the PI3K/AKT Signaling Pathway.

Published 17th May, 2024

https://doi.org/10.1016/j.jep.2024.118364

Related Studies

2) The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway.

https://doi.org/10.1128/MCB.00099-20

3) Wogonin and its analogs for the prevention and treatment of cancer: A systematic review.

https://doi.org/10.1002/ptr.7386

4) Drug-induced liver injury: Pathogenesis, epidemiology, clinical features, and practical management.

https://doi.org/10.1016/j.ejim.2021.10.035


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