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Contact with Gynura plants causes liver damage in rats and liver cells

tabnews August 18, 2024
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Jim Crocker
17 August 2024



Image source: Chris F (photographer)

Key findings

  • The study by the Shandong Center for Disease Control and Prevention found that Gynura japonica caused significant liver damage in rats
  • Contact with G. japonica resulted in liver cell death by apoptosis, which was associated with changes in mitochondrial function and increased caspase-3 activity
  • The research highlights the need for public awareness and accurate identification of herbal remedies to prevent exposure to toxins.
Gynura japonica (Thunb.) Juel, an herb commonly used in traditional medicine, is associated with significant liver toxicity. Often confused with nontoxic herbs such as Tu-San-Qi (Sedum aizoon L.) and San-Qi (Panax notoginseng L.), Gynura japonica contains pyrrolizidine alkaloids (PAs), which are known to cause hepatic sinus obstruction syndrome (HSOS) in over 50% of cases.[1]. Despite its widespread use, the mechanisms underlying its liver toxicity have remained unclear. Recent research from the Shandong Center for Disease Control and Prevention aimed to elucidate these mechanisms by investigating the toxic effects of a G. japonica decoction on liver and Buffalo Rat Liver (BRL) cells. In this study, researchers administered a G. japonica decoction to Sprague-Dawley rats to observe its effects on liver function and tissue damage. They used bioinformatics analysis to identify gene expression and pathways associated with liver toxicity. Advanced techniques such as confocal laser scanning microscopy and flow cytometric Annexin-V/PI labeling assays were employed to observe apoptosis in BRL cells. Additionally, transmission electron microscopy and JC-1 staining were used to evaluate mitochondrial ultrastructure and membrane potential. The study also measured the expression of apoptosis-related proteins and caspase-3 activity using the bicinchoninic acid method and enzyme immunoassays. The results showed that exposure to G. japonica in rats caused significant liver damage, as evidenced by changes in body weight, liver histology, and serum liver function-related indices. Bioinformatics analysis suggested that the observed liver toxicity was related to apoptotic signaling pathways, positive regulation of programmed cell death, and responses to toxic substances. BRL cells exposed to G. japonica decoction showed mid- to late-stage apoptosis and necrosis, as well as notable changes in mitochondrial morphology and membrane potential. In addition, there was an increased expression of cytochrome C (Cyt C) and pro-apoptotic proteins, a decrease in anti-apoptotic proteins, and increased caspase-3 activity. These results are consistent with previous studies that have highlighted the hepatotoxic potential of the pyrrolizidine alkaloids found in G. japonica. For example, it has been documented that G. japonica can lead to HSOS, which is characterized by obstruction of the liver sinusoids and central veins.[2][3]The study also supports previous findings that pyrrole-protein adducts (PPAs), biomarkers for PA-induced HSOS, persist longer in the liver than in serum, suggesting prolonged exposure of the liver to toxins.[2]. The present study expands our understanding by revealing the role of mitochondria-mediated apoptosis in liver toxicity caused by G. japonica. This mechanism involves the disruption of mitochondrial membrane potential and the release of Cyt C, which triggers a cascade of events leading to cell death. The increase in caspase-3 activity further confirms the activation of the apoptotic pathway. These findings are crucial for developing targeted therapies and improving clinical treatment of PA-induced liver injury. Furthermore, this research highlights the importance of raising public awareness of the potential toxicity of herbal remedies. Misidentification of G. japonica with nontoxic herbs can result in serious health consequences. Therefore, accurate identification and regulation of herbal products are essential to prevent inadvertent exposure to toxic compounds. In conclusion, the study conducted by the Shandong Center for Disease Control and Prevention provides a comprehensive understanding of the hepatotoxic mechanisms of G. japonica. By highlighting the role of mitochondria-mediated apoptosis, it provides a scientific basis for clinical therapy and emphasizes the need for caution in the use of traditional herbal medicines.


MedicineHealthPlant Sciences


References

Main study

1) Contact with Gynura japonica (Thunb.) Juel plants causes liver toxicity in liver cells of rats and buffalo rats.

Published on August 14, 2024

https://doi.org/10.1016/j.jep.2024.118692

Related studies

2) The long-term persistence of pyrrole-protein adducts from pyrrolizidine alkaloids in vivo: kinetic study after multiple exposure to a pyrrolizidine alkaloid-containing extract of Gynura japonica.



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