DESCRIPTION
St John's wort is an herbaceous plant used since ancient times for treating wounds and burns, and more recently in the treatment of mild and moderate depression, postpartum depression and seasonal affective disorder (SAD), even if it can not be considered the drug of first choice in severe depression.
HYSTORY
The name comes from the greek "uper" (above) and "eikon" (image) because the plant was hung above the images of the deities to ward off spirits. In Middle Ages it was believed that he was able to drive out the devil because of its incense odor and was called a "devil drives."
It was been used since antiquity as reported Ippocrate and Plinio il Vecchio, during the Middle Ages and in particular by Knights Templar.
COMPOSITION
- naftodiantroni: ipericina, pseudoipericina;
- diantroni: iperico-deidro-diantranolo, protoipericina, ciclopseudoipericina, isoipericina;
- antranoli: emodinantranolo;
- acidi fenilici: acido p-cumarico, acido isoferulico, acido caffeico, acido clorogenico;
- acilfluoroglucinoli (derivati del floroglucinolo): iperforina, adiperforina, iperresina 1 e 2;
- flavonoidi;
- bioflavonoidi;
- procianidine;
- xantoni: 1, 3, 6, 7-tetraidroxantone;
- tannini;
- proantocianidine oligomeriche comprese le procianidineA1, B1, B2, B3, B5, B7, C1 insieme a monomeri della catechina ed epicatechina;
- vitamine A, C;
- monoterpeni;
- olio essenziale contenente principalmente alfa-pinene;
CLASSIFICATION
Herbaceous plant, originating in Great Britain, a perennial and spontaneous in Europe and Asia in areas of the temperate climate that grows on dry and gravelly.
Kingdom: Plantae
Subkingdom: Tracheobionta
Superdivision: Spermatophyta
Division: Magnoliophyta
Class: Magnoliopsida
Subclass: Dileniidae
Order: Theales
Family: Guttiferae
Genus: Hypericum
Species: Hypericum perforatum L.
INDICATIONS
In therapy it's used:
- Extract: 300 mg / day (1 mg hyperforin) in two or three divided doses, preferably between meals. In the case of depression is prolonged administration while in the case of SAD is reduced to eight days.
- Tincture: 50 drops two to three times daily.
Topic uses (5% oil or cream):
- Anti-inflammatory and anesthetic;
- Wounds, burns, pressure sores and itching;
- Skin blemishes, psoriasis, anti-dry skin of face and body and skin aging stretch marks, scars, acne marks caused;
- Hemorrhoids;
- Insect bites;
- Muscle pain and joint pain;
- Antibacterial, antifungal and antiviral.
Other uses:
- Alcholism treatment: correlation between alcholism and depression;
- Enuresis and “pavor nocturnus”;
- Gastritis, gastroduodenal ulcer;
- Insomnia, some forms of hysteria, menstrual disorders and in states of fatigue;
- Improves circulation and heart activity.
Possibly future uses:
Recent studies have demonstrated that hyperforin (potent photosensitiser) inhibits cell growth of human breast cancer cells and rats and acts also against squamous cell carcinoma, melanoma and lymphoma with an efficacy similar to other cytostatic drugs, like paclitaxel or vincristine . Probably the hyperforin induces apoptosis of tumor cells through the release of cytochrome and caspase activation.
More insights:
- monography1;
- monography2.
PHARMACOKINETICS
Data collected from studies conducted mainly on three components: hypericin, hyperforin and pseudo-hypericin. In the treatment of depression, it is to be taken orally.
- Hypericin: 0,3% extract 300-1800mg:
- Maximum concentration: 4-6 hours;
- Bioavailability: 4%;
- Plasma half-life: 25-28 hours;
- Pseudo-hypericin: 0,3% extract 300-1800mg:
- Maximum concentration: 2,5 hours;
- Bioavailability: 21%;
- Plasma half-life: 16-24 hours;
- Hyperforin: 0,3% extract 300-1800mg:
- Maximum concentration: 3 hours;
- Plasma half-life: 9-16 hours;
More insights: Document
MOLECULAR MECHANISM
The most important actions are:
- Antidepressive
- inhibitory mechanism MAOA (strong) and MAOB (mild);
- hyperforin binds to receptors:
- 5HT1d, 5HT2c, 5HT6, 5HT7 and opiate (sigma and kappa);
- D1, D3 and D5 and is a potent inhibitor of uptake of serotonin, dopamine, norepinephrine, γ-aminobutyric acid and glutamic acid;
- activation of the exchanger Na + / H +;
- increasing of neurotransmitters and inhibition of COMT;
- increased concentrations of adrenaline, noradrenaline and DOPA;
- flavonoids:
- interaction with GABA-benzodiazepines receptors.
- quercitina:
- related to GABA;
- Arrest serotonin reuptake.
- Antiviral (HIV, HSV1-2, Parainfluenza virus, EBV, CMV);
- hypericin (hypotesys of action):
- Action at both the assembly or the anchor of viral;
- Binds to the lipid membrane of the virus, which absorbs a photon with training, through a mechanism that would act then to photo-activation level of the link between HIV gp120 and CD4 receptor of Th, with inhibition of viral fusion and the formation of syncitia;
- action is directed against the capsid of the virus and which inhibits or radically alter the mobility;
- Antibacterial;
- oils;
- floroglucinoli;
- flavonoidi;
- tannini.
- Inflammatory (document1, document2):
- extract hydro-alcoolic inhibits lipoxygenase without effects on COX-2;
- SJW extract suppress the inflammatory response leukocyte infiltration.
NOTE: another possibility to explain the action of St. John's wort comes from theories of psychoneuroimmunology, which explain how cytokines, especially interleukins, act by activating the hypothalamic-pituitary-adrenal axis. Not only is St. John's wort contains cytokines but apparently following its administration is observing un'ipersecrezione of ACTH by the pituitary and, consequently, cortisol, and then to St. John's Wort affects negatively the production and interleukin 6 (IL - 6), implicated in the induction of depression in susceptible individuals.
NOTE: light-activated hypericin is toxic to cancer cells, but the data are still scarce. The problem of dose-effect for cancer treatment has not yet been clarified. Thomas-Bradley reports that the light-activated hypericin exhibits dose-dependent activity in laboratory tests on breast cancer in mice and human.
SIDE EFFECT AND TOXICITY
The problem reppresented by the use of hypericum is its interaction with some drugs.
Many observers have pointed out how the St. John's wort reduces the concentration and thus the therapeutic effect of many substances through a process of enzyme induction. This translates into a more rapid and intense metabolism of the drug will lose its effectiveness. Unlike the abrupt discontinuation of SJW may lead to rebound, massive blood concentrations of the drug which had increased the dosage to achieve the same therapeutic effect.The drug interaction is the induction of cytochrome P450 in the liver, CYP3A4, CYP1A2, CYP2C9.
More insights: monography2.
Side effects are uncommon and minor entity:
- gastrointestinal disturbances, dry mouth;
- headache, dizziness, mental confusion;
- allergic reactions;
- redness, burning and itching in areas exposed to the sun for his photo sensitizing properties;
- blood pressure rising;
- hypothyroidism for high values of TSH and stimulate the secretion of growth hormone and adrenocorticotropic hormone (ACTH and GH) by the adrenal glands.
In very rare cases it can have detrimental effects, especially where they are consumed large amounts of SJW for self-medication with the simultaneous intake of synthetic antidepressants (such as tricyclics or fluoxetine):
- serotonin syndrome, caused by excessive activity in the CNS probably by activating serotonin receptor 5HT1a, with the possible involvement of dopamine and 5HT2 receptors.
The mutagenic effects, potentially due to quercetin, is invalid, even for the fact that it is present in fruits and vegetables, as well as in medicinal plants, and is taken daily to tens of milligrams per day.
CONTROINDICATIONS
During pregnancy it is advisable not to use or use with caution. Not for use during lactation and in children aged less than 12 years. Do not use after organ transplantation and in HIV-positive subjects receiving protease inhibitor-1.
