Something against autumn blues…

Summer is almost over in Italy, but before moving on to the next season, I would like to talk about a plant that is somehow strongly connected to summer: Saint John’s Wort.

Plants are wonderful organisms and some of their features make them look like magical beings to humans. If we have a look at popular traditions and beliefs, many are related to plant species. For example, ever wondered why Saint John’s Wort is called like this? There are several legends related to the origin of the name of this species. Its scientific name is Hypericum perforatum, however, it is by far mostly known by the common name. One of the possible origins of the name is related to the red oil secerned by its glandular trichomes, which was believed to be Saint John’s blood by the first Christians (1).
The legends related to this plant do not end here. Indeed, it was part of a list of 9 plants that would need to be collected at the summer solstice night, believing that this was the moment in which their properties reached the maximum level (1). In Medieval ages people would sleep with some hypericum under their pillow on Saint John’s day (1). However, the fortune of this plant dates far back, to the ancient Rome where it was symbol of light and sacred to Jove (1). The myths are numerous and, as often happens with traditional medicine, they converged in the use of this plant for healing purposes and it is sometimes hard to understand where the legend ends, and the science starts. However, we now know a lot about this plant, its chemistry, and the medicinal properties.

Hypericum perforatum belongs to a genus that lists many species. Among them St. John’s wort, is the best-known (2). However, also other Hypericum species have been included in traditional medicines systems in many countries around the world or are sold as ornamentals (2).
Hypericum perforatum is a perennial herb, native to Eurasia but now distributed to all other continents, except for Antartica (2). Its flowering tops are usually prepared as a decoction or infusion and taken as sedatives or tonics (3). The oil-infusion is used to treat sciatica, neuralgia, and speed up wound-healing (3). Extracts of the inflorescences and upper stem leaves have been prescribed for many years in Europe and are available as dietary supplements in the United States, to treat mild to moderate depression (4). However, concerns have been raised about Hypericum use, due to several reasons. First of all, although the short-term effect on mild and moderate depression has been shown, the long-term effects are far less known. Furthermore, studies aimed at understanding its efficacy gave mixed results, while, on the other hand, it was shown that it interacts with many drug active principles, amplifying the effects of prescription antidepressant and weakening the effects of other drugs (5,6). Finally, it is often easy to fall victim to the misconception that natural means safe with a consequent wrong use or even abuse of the drug.

Several classes of bioactive specialized metabolites have been identified from extracts of Hypericum perforatum, including flavonoid derivatives, naphthodianthrones, phloroglucinol derivatives and xanthones (3). Among these, hypericin and hyperforin are the most interesting ones. The latter, a prenylated phloroglucinol, is the main responsible for the antidepressant activity. Hyperforin inhibits the uptake of several neurotransmitters from the synapse into the pre-synaptic neuron (7), therefore increasing the extracellular concentrations of the neurotransmitters. The activity is exerted by elevating the intracellular sodium concentration in the presynaptic neuron, thereby inhibiting the gradient-driven neurotransmitter reuptake (7). Also hypericin, a naphthodianthrone, seems to have a role in the antidepressant effect of Hypericum perforatum. These two compounds have actually also other properties, and we will surely have the chance to further discover and analyse them in the future, having also a deeper look at their mechanisms of action.

Why does Hypericum perforatum synthetize such complex chemicals? Although we do not know exactly yet which specific role they have in planta, they might be involved in the plant defence system. Indeed, it was shown that the levels of hypericin and hyperforin are increased in response to abiotic and biotic stresses (8,9). Furthermore, the treatment of Hypericum perforatum with chemicals that are known to mimic the induction of stresses also induced an increase of their levels (8), suggesting that these specialized metabolites are components of the inducible plant defence response.

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