## Secondary metabolites of St. John's wort

A plant currently receiving significant attention in research is St. John's Wort (Hypericum perforatum L.) and is one of the most commonly used medicinal plants in the world. It is widespread in Europe, Asia, North America, and North Africa, with its species name derived from the dots on the flowering parts and leaves. These tiny perforations and dark glands are vital because they contain the most effective compounds of St. John's Wort. The effects of these natural substances have been known for more than 2,000 years, which is why St. John's Wort was often used to treat burns, clean wounds, reduce swelling, and alleviate depression. The ancient Greeks and Romans believed that St. John's Wort expelled evil spirits and was called the "balm for the wounded soul". But what is behind these properties of this inconspicuous plant? In experiments that studied the chemical composition of St. John's Wort extracts, the metabolite hyperforin was discovered, which is found in bright glands mainly on the leaves of this plant. This substance acts as a sedative and is psychoactive drug with euphoric effects, therefore it is used in treating neuroses, depression, and migraines. Hyperforin acts similarly to prescription antidepressants by blocking the reuptake of neurotransmitters, such as norepinephrine, serotonin, and dopamine. These substances are naturally present in the brain and help regulate a person's mood and emotions. They are the chemical messengers that transmit information between individual nerve cells, and their imbalance can cause depression, anxiety, or fatigue. In addition to being able to release these messengers, the cell can also take them up again (reuptake). This is where hyperforin works, acting on the sodium transporter, increasing its intracellular concentration and thus indirectly blocking the mechanisms responsible for neurotransmitter reuptake. Thanks to this mechanism, the concentration of neurotransmitters in the brain increases, which causes a feeling of happiness and improves the patient's mood.

Another significant metabolite of St. John's Wort is hypericin, present in the dark glands on the plant's above-ground parts, especially on the flowers. Hypericin has many effects (e.g., anti-inflammatory, antimicrobial, and others) that are useful in various branches of medicine. However, it is always important to remember that the plant does not produce these phytochemicals for us to use in biomedicine but instead tries to protect itself through them. This phenomenon is called hypericism and protects the plant from being eaten by predators. Hypericin is an illustration of hypericism and the protective effect of metabolites: cattle which graze on St. John’s Wort experience adverse health effects specifically inflammation of the skin and sun sensitivity associated with paralysis. However, these processes can be utilised to treat oncological diseases through photodynamic therapy. As its name suggests, photodynamic therapy is based on the change in the dynamics of the drug depending on the light stimulus (and the presence of molecular oxygen). This therapeutic approach is mainly used to treat skin diseases and tumours. Hypericin is injected into the patient's body and preferentially accumulates in the tumour tissue (Figure 11.4) and subsequently the target area is irradiated through optical fibres. After irradiation, hypericin is excited, which in this state interacts more intensively with its surroundings, whether it is individual cell components or oxygen present in cells. This process triggers the formation of reactive oxygen species (for more details, see Chapter 8 - Your cells are stressed too), which ultimately destroys tumour cells. This therapy results in the selective destruction of tumours without excessive damage to surrounding tissue, as hypericin preferentially binds to tumour cells. Currently, several substances are used as photosensitisers, but hypericin still plays a significant role in this type of therapy. In addition, hypericin can also be used in diagnostics, as it can release fluorescence after irradiation, thus helping surgeons mark the boundaries of the tumour and the presence of possible metastases in the patient's body.

In conclusion, we can state that plants are extraordinary organisms that represent a large part of our biosphere and can be used in several more ways than just as a food source. Since they cannot avoid adverse environmental factors and change their location, they have to deal with the traps of their surroundings during evolution and adapt to them. In this way, they indirectly provide us with various strategic approaches and medicinal compounds, which are also interesting for human medicine. But before that, it is necessary to properly understand these mechanisms of defence and production of phytocompounds at the molecular level so that we can use them as effectively as possible.