How Clock Protein Affects Melatonin Production in St. John's Wort

Greg Howard
20th September, 2024

How Clock Protein Affects Melatonin Production in St. John's Wort

Image Source: Natural Science News, 2024

Key Findings

  • Researchers at Shaanxi Normal University discovered that melatonin synthesis in St. John's wort is regulated by an internal circadian clock
  • The clock protein HpLHY binds to the melatonin biosynthesis gene HpSNAT1, inhibiting its expression in a 24-hour cycle
  • Overexpressing HpLHY reduces melatonin levels, while loss-of-function mutants increase melatonin levels, confirming HpLHY's crucial role
Hypericum perforatum, commonly known as St. John's wort, is widely recognized for its antidepressant properties and is often referred to as "natural fluoxetine." Recent research conducted by Shaanxi Normal University has explored the regulation of melatonin in this plant, uncovering mechanisms that could have significant implications for understanding melatonin synthesis in plants and its potential therapeutic applications[1]. Melatonin, a hormone known for regulating sleep-wake cycles in vertebrates, is also present in plants, where it plays various roles, including growth regulation and stress response. However, the regulation of melatonin in plants has not been as extensively studied as in animals. The study aimed to investigate whether melatonin synthesis in H. perforatum follows a circadian rhythm similar to that in vertebrates. The researchers constructed a yeast complementary DNA library of H. perforatum and identified a clock protein named HpLHY. This protein was found to bind directly to the promoter of the melatonin biosynthesis gene, serotonin N-acetyltransferase HpSNAT1. Further experiments confirmed that HpLHY inhibits the expression of HpSNAT1 by targeting a specific DNA sequence known as the Evening Element. This regulatory mechanism was shown to oscillate in a 24-hour cycle, indicating that melatonin synthesis in H. perforatum is indeed regulated by an endogenous circadian clock. To further validate these findings, the researchers generated HpLHY-overexpressing plants and loss-of-function mutants. They observed that overexpression of HpLHY led to reduced melatonin levels under a 12-hour light/12-hour dark cycle, while loss-of-function mutants exhibited increased melatonin levels. Interestingly, this rhythmic pattern of melatonin synthesis appeared to dissipate in the absence of functional HpLHY, highlighting its crucial role in maintaining the circadian regulation of melatonin biosynthesis. These findings provide a deeper understanding of how melatonin synthesis is regulated in plants and could have broader implications for the use of H. perforatum in therapeutic applications. For instance, melatonin is known for its antioxidant properties, and its regulation in plants could influence the overall efficacy of H. perforatum as an herbal remedy. The study also ties into earlier research on the therapeutic effects of H. perforatum and its active components. Previous studies have demonstrated the antidepressant and antitumor properties of St. John's wort, largely attributed to its ability to inhibit monoamine neurotransmitter re-uptake and modulate inflammatory mediators[2]. Additionally, clinical trials have shown that St. John's wort is as effective as standard SSRIs (Selective Serotonin Reuptake Inhibitors) in treating mild-to-moderate depression, with fewer side effects and lower discontinuation rates[3]. The interaction between H. perforatum and other medications has also been a topic of interest. For example, Traditional Chinese Medicine (TCM) often incorporates herbs that could interact with pharmaceutical drugs like clopidogrel. Some herbs have been shown to either increase or decrease the efficacy of clopidogrel, highlighting the importance of understanding these interactions for better therapeutic outcomes[4]. In summary, the recent study by Shaanxi Normal University provides valuable insights into the circadian regulation of melatonin synthesis in H. perforatum, adding another layer of understanding to its therapeutic potential. By elucidating the role of the clock protein HpLHY in regulating melatonin biosynthesis, the research opens new avenues for optimizing the use of St. John's wort in various medical applications, including its role as an antidepressant and its interactions with other medications.

GeneticsBiochemPlant Science

References

Main Study

1) Clock protein LHY targets SNAT1 and negatively regulates the biosynthesis of melatonin in Hypericum perforatum.

Published 20th September, 2024

https://doi.org/10.1126/sciadv.adq6505

Related Studies

2) Anti-Tumor Activity of Hypericum perforatum L. and Hyperforin through Modulation of Inflammatory Signaling, ROS Generation and Proton Dynamics.

https://doi.org/10.3390/antiox10010018

3) Clinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis.

https://doi.org/10.1016/j.jad.2016.12.048

4) Interactions between clopidogrel and traditional Chinese medicine.

https://doi.org/10.1007/s11239-019-01945-3


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