How St. John's Wort Ingredients Harm Liver Cells

Greg Howard
15th January, 2024

How St. John's Wort Ingredients Harm Liver Cells

Image Source: Natural Science News, 2024

St. John's Wort is often used to relieve mild to moderate depression because it’s generally believed to be safe. However, in some rare cases, it can cause liver damage, and scientists aren't sure exactly why. Researchers have taken a closer look at the effects of St. John's Wort’s main components, hypericin and hyperforin, on liver cells. They wanted to understand how these substances could be harming mitochondria, the cell’s powerhouses, which if damaged, can lead to liver toxicity. The study used two types of liver cells, HepG2 and HepaRG, and the effects of hypericin and hyperforin were compared with citalopram, a known antidepressant. Results showed that hypericin could be harmful to cell membranes and seriously deplete the cells' energy source, ATP, in HepG2 cells at concentrations of 20µM and above. This depletion happened at even lower levels (5µM) in HepaRG cells. Hyperforin and citalopram, on the other hand, showed no toxic effects even at higher levels. Hypericin also negatively affected the cells’ ability to breathe at a molecular level, disrupting the flow of electrons needed for making ATP. The problem began at concentrations as low as 2µM, indicating that even small amounts could potentially impair mitochondrial function. It also didn’t affect the production of ATP from non-mitochondrial sources. On a closer look, hypericin was found to inhibit key components of the mitochondrial electron transfer system: complexes I, II, and IV. This disruption led to the mass production of harmful superoxide molecules in the mitochondria. Moreover, the study found that exposure to hypericin diminished the cell’s defenses by reducing the levels of proteins involved in neutralizing harmful substances, such as SOD2 and TRX2, and decreasing both total and available antioxidants, like glutathione. In addition, hypericin was shown to lower the number of copies of mitochondrial DNA in cells and led to cell necrosis – a form of cell death where cells are damaged and die prematurely. Interestingly, it didn't trigger apoptosis, which is a more controlled form of cell death. The takeaway from this research is that while not all ingredients in St. John's Wort are harmful, hypericin specifically can be toxic to liver cell mitochondria. Even in low doses, it can significantly disrupt cellular functions, possibly contributing to the liver toxicity seen in rare cases with St. John’s Wort usage. These findings help explain why some patients might experience liver damage when treated with preparations of the plant. Understanding the toxic effects of hypericin on mitochondria might guide the development of safer therapeutic practices for individuals using St. John's Wort for depression.



Main Study

1) Mechanisms of hepatocellular toxicity associated with the components of St. John's Wort extract hypericin and hyperforin in HepG2 and HepaRG cells.

Published 12th January, 2024

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