Articles

St. John's Wort

Plant Part Used

Flowering buds

Active Constituents

Napthodianthrones (hypericin, pseudohypericin protohypericin, protopseudohypericin), flavonoids (including rutin, quercitrin(37), isoferulic acid, hyperoside, quercitin, isoquercitrin, hyperoside, astilbin, miquelianin, I3,II8-biapigenin (38)), phloroglucinols (hyperforin and adhyperforin (38)), melatonin(1),(2)  and phenolic acids (chlorogenic acid, 3-O-coumaroylquinic acid).(38) [span class=alert]

This section is a list of chemical entities identified in this dietary supplement to possess pharmacological activity. This list does not imply that other, yet unidentified, constituents do not influence the pharmacological activity of this dietary supplement nor does it imply that any one constituent possesses greater influence on the overall pharmacological effect of this dietary supplement.[/span]

Introduction

St. John’s wort has gained a great deal of attention for its use in minor depression. Its popularity has stemmed from its extensive use by physicians in Europe as an agent of choice in the treatment of mild to moderate depression. There are a variety of studies which are claimed to support the use of St. John’s wort in treating mild to moderate depression. (3) , (4) , (5) Also, sales of this herb in Europe, based on physician recommendation, outperform the popular pharmaceutical fluoxetine (Prozac). It is reported that during the floral bud stage of St. John’s wort, the concentration of napthodianthrone compounds is at the highest. (39)

Results from two independent randomized controlled trials have indicated that St. John's wort is no more beneficial than placebo in individuals with major depression. However, one of these trials used sertraline (50 to 100 mg/day) as an active control and found no significant superiority of sertraline over placebo in this patient population as well. Though these two trials may indicate that St. John’s wort is not effective for major depression, they neither confirm nor deny the use of St. John's wort in mild to moderate depression.(6) , (7) More recent meta-analysis support the use of St. John’s wort for use in mild to moderate depression.(40) , (41)

Interactions and Depletions

Interactions

Dosage Info

Dosage Range

900mg (standardized extract) daily, in divided doses. (Some individuals may experience benefit with as little as 300-600mg daily.) Higher doses are used in viral infections, and should only be performed under the supervision of a doctor.

Topically: Apply oil extract as needed to affected area(s).

Liquid Extract: 1:1 in 25% ethanol – 2-4 milliliters, 3 times a day. (8)

Tincture: (1:10) in 45% ethanol – 2-4 milliliters, 3 times a day. (9)

Most Common Dosage

300mg (standardized extract), 3 times a day.

Topically: Apply oil extract as needed to affected area(s).

Liquid Extract: 1:1 in 25% ethanol – 2 milliliters, 3 times a day.

Tincture: (1:10) in 45% ethanol – 2 milliliters, 3 times a day.

Standardization

[span class=doc]Standardization represents the complete body of information and controls that serve to enhance the batch to batch consistency of a botanical product, including but not limited to the presence of a marker compound at a defined level or within a defined range.[/span]

The most current available medical and scientific literature indicates that this dietary supplement should be standardized to 0.3-0.5% hypericin and/or 3-5% hyperforin per dose.

Uses

Frequently Reported Uses

  • Antiviral.
  • Depression
  • SAD (Seasonal Affective Disorder)
Other Reported Uses
  • Myalgia
  • Neuralgia
  • Fear
  • Genitourinary
  • Externally For Bruises, Sprains (Leaf)
  • HIV And Retroviruses
  • Nervous Symptoms Associated With Menopause And PMS
  • Wound Healing
  • Diuretic
  • Antibiotic
  • Nootropic

Toxicities & Precautions

General

Although no real evidence has been presented to support it, there is theoretically a potential for an interaction with tyramine-containing foods, so these foods should be avoided. (10)

Based on evidence that St. John’s wort may cause changes in the need for certain medications, do not use St. John’s wort supplements if you are taking prescription and/or OTC medications without the advice of your doctor or pharmacist.

Allergy

Allergic reactions have occurred in a small percentage of individuals who use St. John's wort.

Health Conditions

Should not be taken in suicidal depression, psychosis or severe depression.

St. John's wort has affected the metabolism of certain medications via alteration of P-glycoprotein and cytochrome P-450 3A4 expression. Changes in cyclosporine levels have been confirmed. Based on human data, do not use St. John’s wort in transplant patients. Complications as well as transplant rejection have occurred with the use of this herb. (11) , (12)

Photosensitivity

Based on pharmacology, animal data and human data, may cause photosensitivity. (13)

May cause photosensitivity in high doses such as those used by the AIDS population. (14)

Side Effects

Fatigue and GI distress may occur in about 0.5 percent of the individuals who take St. John’s wort.

Based on animal studies, it may induce liver enzymes in large doses, but these return to normal with discontinuation. (15)

217 out of 440 patients treated with St. John’ s wort for one year were reported to have adverse events, including gastrointestinal (abdominal pain or gastritis) and skin (rash or pruritus) being the most common. (42)

A study conducted on rats and human using electric field stimulation test reported that St, John’s wort inhibits the contraction of vas deferens that indirectly delays ejaculation function, potentially due to the hyperforin constituent content. (43)

Pregnancy/ Breast Feeding

Based on animal studies, do not use in pregnancy. (16) , (17)

Age Limitations

Do not use in children under 2 years of age unless recommended by a physician.

Pharmacology

St. John’s wort is a perennial flowering plant, which grows in many areas of the world, including Europe and the United States. The parts of the plant used are the portions above the ground. Studies with St. John’s wort have centered around the use of a 0.3 percent hypericin content standardized extract at a dose of 300mg, three times a day. It is viewed as safe and effective in Europe and its monograph is part of the Commission E Monographs for herbal medicines in Europe.

St. John’s wort is believed to have several possible effects on body chemistry. These include:

    The inhibition of cortisol secretion and the blocking of catabolic hormones, such as interleukin 6 (IL-6). (18)

    The inhibition of the breakdown of several central nervous system neurotransmitters, including serotonin. It may have mild MAO-inhibiting activity. This has not been clearly defined and cannot explain all the activity of St. John’s wort. Researchers do not consider this to be its major mechanism of action. (19) , (20) , (21) A laboratory study in mice reported that St.John’s wort increased sleeping duration and increased open arm entries indicating sedating and anxiolytic effect. (44) In addition, St. John’s wort has inhibitory ability of acetylcholinesterase although not as potent as Hypericum androsaemum. (45)

    St. John’s wort may amplify and improve the signal produced by serotonin once it binds to its receptor sites in the brain. (22) , (23) A study reported that when the efficacy of St.John’s wort was compared with selective serotonin reuptake inhibitor (SSRI) for the treatment of major depressive disorder, both showed similar and positive results with St. John’s wort having a lower withdrawal adverse events. (46)

    St. John’s wort contains the chemical melatonin (approximately 4.39 mcg/gm), which may also contribute to the antidepressant effects of the plant. (24) Pseudo-hypericin and hyperforin may enhance serotonin, catecholamines, and glutamine levels in the brain.

     

A study on the relationship between nicotine withdrawal from smoking cessation with the antidepressant effect from St. John wort’s reported significant results in the increase of serotonin content in St. John’s wort treated mice having nicotine withdrawal. (47) However, large doses of St. John wort’s should be used with caution since studies have reported that when rats are treated with 200mg/kg for 3 days, prepulse inhibition occurs causing problems in managing memory process disturbances.(48)

A human trial reported improvement in symptoms of attention-deficit hyperactive disorder (ADHD) when using St. John’s wort, as found when testing with Conners’ hyperactivity.(49)

Additionally, Hypericum has been used as an antiviral agent, including HIV. (26) It has been reported that, in sufficient blood levels, it may decrease HIV titer and it may increase T-killer cell activity. (27) Hypericum and the xanthrones are thought to be responsible for the antiviral activity. (28) Although its antiviral action has been questioned, several studies report this potential action. (29) , (30) The drawback is that large doses must be taken and this is where side effects related to St. John’s wort (such as phototoxicity) can occur. However, if compared with pure hypericin, administrating St. John’s wort which contained the same compound will cause lesser skin photosensitization reactions. (50) A recent study has reported no positive effect when using St. John’s wort as an antiretroviral agent. (31) If an individual is taking protease inhibitor medications do not use St. Johns wort as a therapy for HIV due to changes in liver metabolism of these agents.(32) Also, since anti-retroviral agents are hepatically metabolized, use extreme caution when taking these medications and St. John’s wort. Use only under the direction of a physician. A study reported that when tested on pigs infected with porcine respiratory and reproductive syndrome virus, the St. John’s wort is effective in reducing the virus in the blood stream but not significant in playing a role in reducing the virus in the lungs.(51) In addition, St. John’s wort plays a role as an anti-hepatitis B agent as studies report that it is able inhibit viral antigens by affecting the transcription of hepatitis-B virus.(52)

Although St John’s wort is reported to have antimicrobial activity as well, it is the least potent among other plant extracts when tested on antimicrobial assay.(53)

Recent literature has reported cytochrome P-450 enzyme-inducing activity of St. John’s wort in human studies. Interactions between St. John’s wort and anticoagulants, indinavir, cyclosporin, digoxin, ethinyloestradiol/desogestrel and theophylline have occurred.(33) The mechanism of action was believed to be liver enzyme induction and subsequent alterations of drug levels by the herb. Also, several reports have suggested that concurrent use of St. John’s wort and SSRIs may result in "serotonin syndrome," including sweating, tremor, confusion, flushing and agitation.(34),(35) Use St. John’s wort with caution if individuals are on these medications.  However, interaction between bromocriptine and St. John’s wort reported to have synergistic effect in treating MPTP- induced Parkinson’s disease by improving movement performance, reducing dopamine level and decreasing corpus striatum antioxidant level.(54)

St. John’s wort has also been used topically to increase wound and burn healing, as well as for myalgia and neuralgia.(36) It is reported that the healing effect is due to the ability of the herb to activate and also produce fibroblast cells and collagen which has the same potency as Centella asiatica plant. (55) Another study further supports the wound-healing ability by showing tissue regenerating, improved tensile strength and epithelization due to the anti-inflammatory hyperforin component. (56) A laboratory study reported that this anti-inflammatory effect was due to two pathway mechanism identified as JAK-STAT pathway and eicosanoid pathway, which reduced prostaglandin-E2 production. (57) The use of St. John’s wort in pain management is reported to be effective in the treatment of dental pain when homeopathic Hypericum perforatum was the preferred remedy for pain, including post extraction pain and swelling. (58)

When acute inflammation is induced with carrageenan in the lungs of mice, St. John’s wort was found to reduce the tissue injury by playing a role in the neutrophils and proinflammatory cytokines as well as up-regulation of poly(ADP) ribose and activation of redox-sensitive transcription factor and other transcription factors like STAT-3. (59) This is further supported by another animal study whereby multiple organ dysfunction induced by oxidative stress in mice was reduced by St John’s wort due to its ability to reduce inducible nitric oxide synthase which subsequently prevent formation of nitric oxide. (60) In addition, the ability of St. John wort’s to reduce oxidative stress is reported in a study whereby the flavanoid constituent of the herb is able to inhibit peroxyl radicals induced by AAPH (inductor of lipid peroxidation). (61) An animal study reported that St John’s wort have the potential to protect liver injury (ischemia reperfusion) in rats treated with the herb for a week due to its antioxidant effect. (62)

St. John’s wort extract is reported to be effective in causing apoptosis towards bladder cancer cells when used in photodynamic therapy due to its ability as a photosensitizer. (63)

A laboratory animal study found that ingestion of St. John’s wort by 20 rabbits as diet regime for 45 days followed by regular diet and St. John’s wort for 30 reduced cholesterol levels, leading to a decrease in the progression of atherosclerosis. (64)

The therapeutic ability of St. John’s wort to reduce sensitivity to pain stimuli was reported when administered to rats with thermal-induced and chemical-induced pain. (65) Hypericin and hyperforin are the main constituents responsible for increasing the pain threshold. St. John’s wort has been used in dressing wounds, along with soluble collagen and gotu kola.

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