Hypericum is a photosensitising & toxic plant

[Guest guest]

Hi Bill, & All,

 

Re: Photo-urticaria, Bill Schoenbart wrote:

> Hypericum isn't hepatotoxic. Millions of doses are taken of Saint Johns

> Wort every year with no sign of liver damage. Did you mean to say

> something else? Bill

 

Bill, you are correct - Hypericum usually is NOT classed as a hepatoxin, but

as a photosensitising agent. It is, however, classed as a toxic plant by some

authorities.

 

That said, ALL of our drugs (pharmacological and herbal) are protentially

toxic:

(1) at excessive dosages

and/or

(2) in patients with metabolic problems that reduce their capacity to handle

intermediary metabolites

and/or

(3) due to interactions with other drugs / herbs

 

Hypericum (like basic essentials for life, such as air, water and common

salt) is no exception. For example, see:

http://vet.purdue.edu/depts/addl/toxic/plant38.htm and

http://www.cfsan.fda.gov/~djw/pltx.cgi?QUERY=Hypericum+perforatum and

www.cbif.gc.ca/pls/pp/ppack.info?p_psn=39 & p_type=all & p_sci=sci & p_x=px

 

http://www.ivis.org/special_books/knight/chap4b/ivis.pdf says: Hypericin, a

photoreactive pigment, is readily absorbed from the digestive tract and

remains chemically intact through the digestion process. Hypericin has no

effect on the liver and causes primary photosensitization after ingestion

[147]. Hypericin is present in the glandular dots on the leaves suggesting

that all Hypericum spp. with similar glands are potentially toxic. Hypericin is

stable to drying and therefore hay containing St John´s wort may cause

poisoning. The young plants are as toxic as the mature plant and more

palatable to livestock although the content of hypericin varies with growing

conditions of the plant [148]. Hypericin has found recent popular use in

people as an herbal stimulant and will induce photosensitivity in some

individuals, especially if overdosed.

 

See also:

 

Aust Vet J. 2004 Nov;82(11):707-10. Reassessment of the toxicity of

Hypericum perforatum (St John's wort) for cattle. Bourke CA, White JG.

NSW Agriculture, Orange Agricultural Institute, Forest Road, Orange, New

South Wales. OBJECTIVE: To investigate the clinical effect of

administering sufficient Hypericum perforatum to cattle to deliver quadruple

the reported oral toxic dose. ANIMALS: Thirty-six yearling Hereford (n = 18)

and Angus (n = 18) steers. DESIGN: A series of six experiments was

conducted, each using 12 animals in a 2 x 2 factorial design, with two

breeds of cattle (Hereford, Angus) and two dose levels of hypericin, 1.5

mg/kg (treated group) and 0 mg/kg (control group). Each set of 12 steers

was used in duplicate experiments, with all animals alternated between

treated and control groups. PROCEDURES: Treated groups received finely

milled H. perforatum administered orally in gelatin capsules to provide 1.5

mg hypericin/kg body weight. All cattle were then exposed to direct sunlight

for 5 h per day for 5 successive days. Rectal temperatures were measured

immediately before and at the end of each sunlight exposure session. Rectal

temperature above 40 degrees C, together with some other clinical sign of

hypericin poisoning, was considered indicative of intoxication. RESULTS: No

animals developed a rectal temperature above 40 degrees C or other clinical

signs of hypericin poisoning. CONCLUSIONS: While the reported bovine

oral toxic dose of 3 g dried plant/kg body weight, for flowering stage,

presumed narrow leaved biotype, H. perforatum, is probably correct, the

corresponding dose for hypericin of 0.37 mg/kg is incorrect. Based on its

known concentration in this plant the toxic dose of hypericin for partially

pigmented Hereford-cross cattle is estimated at about 10.5 mg/kg body

weight and more than this for fully pigmented cattle. This would imply that

cattle of the former type should be about 3.5 times better protected against

H. perforatum toxicity than are unpigmented, wool protected, Merino sheep.

Cattle, particularly if fully pigmented, may have a role in grazing

management to control H. perforatum. Publication Types: Clinical Trial

Randomized Controlled Trial Research Support, Non-U.S. Gov't PMID:

15977618 [PubMed - indexed for MEDLINE]

 

Drugs. 2005;65(9):1239-82. Herb-drug interactions: a literature review. Hu

Z, Yang X, Ho PC, Chan SY, Heng PW, Chan E, Duan W, Koh HL, Zhou S.

Department of Pharmacy, Faculty of Science, National University of

Singapore, Singapore. Herbs are often administered in combination with

therapeutic drugs, raising the potential of herb-drug interactions. An

extensive review of the literature identified reported herb-drug interactions

with clinical significance, many of which are from case reports and limited

clinical observations.Cases have been published reporting enhanced

anticoagulation and bleeding when patients on long-term warfarin therapy

also took Salvia miltiorrhiza (danshen). Allium sativum (garlic) decreased the

area under the plasma concentration-time curve (AUC) and maximum

plasma concentration of saquinavir, but not ritonavir and paracetamol

(acetaminophen), in volunteers. A. sativum increased the clotting time and

international normalised ratio of warfarin and caused hypoglycaemia when

taken with chlorpropamide. Ginkgo biloba (ginkgo) caused bleeding when

combined with warfarin or aspirin (acetylsalicylic acid), raised blood pressure

when combined with a thiazide diuretic and even caused coma when

combined with trazodone in patients. Panax ginseng (ginseng) reduced the

blood concentrations of alcohol (ethanol) and warfarin, and induced mania

when used concomitantly with phenelzine, but ginseng increased the

efficacy of influenza vaccination. Scutellaria baicalensis (huangqin)

ameliorated irinotecan-induced gastrointestinal toxicity in cancer

patients.Piper methysticum (kava) increased the 'off' periods in patients with

parkinsonism taking levodopa and induced a semicomatose state when

given concomitantly with alprazolam. Kava enhanced the hypnotic effect of

alcohol in mice, but this was not observed in humans. Silybum marianum

(milk thistle) decreased the trough concentrations of indinavir in humans.

Piperine from black (Piper nigrum Linn) and long (P. longum Linn) peppers

increased the AUC of phenytoin, propranolol and theophylline in healthy

volunteers and plasma concentrations of rifamipicin (rifampin) in patients

with pulmonary tuberculosis. Eleutheroccus senticosus (Siberian ginseng)

increased the serum concentration of digoxin, but did not alter the

pharmacokinetics of dextromethorphan and alprazolam in humans.

Hypericum perforatum (hypericum; St John's wort) decreased the blood

concentrations of ciclosporin (cyclosporin), midazolam, tacrolimus,

amitriptyline, digoxin, indinavir, warfarin, phenprocoumon and theophylline,

but did not alter the pharmacokinetics of carbamazepine, pravastatin,

mycophenolate mofetil and dextromethorphan. Cases have been reported

where decreased ciclosporin concentrations led to organ rejection.

Hypericum also caused breakthrough bleeding and unplanned pregnancies

when used concomitantly with oral contraceptives. It also caused serotonin

syndrome when used in combination with selective serotonin reuptake

inhibitors (e.g. sertraline and paroxetine).In conclusion, interactions between

herbal medicines and prescribed drugs can occur and may lead to serious

clinical consequences. There are other theoretical interactions indicated by

preclinical data. Both pharmacokinetic and/or pharmacodynamic

mechanisms have been considered to play a role in these interactions,

although the underlying mechanisms for the altered drug effects and/or

concentrations by concomitant herbal medicines are yet to be determined.

The clinical importance of herb-drug interactions depends on many factors

associated with the particular herb, drug and patient. Herbs should be

appropriately labeled to alert consumers to potential interactions when

concomitantly used with drugs, and to recommend a consultation with their

general practitioners and other medical carers. Publication Types:

Review PMID: 15916450 [PubMed - indexed for MEDLINE]

 

Dtsch Med Wochenschr. 2006 May 26;131(21):1214-7. Comment in:

Dtsch Med Wochenschr. 2006 Aug 25;131(34-35):1880-1; author reply

1882-3. Dtsch Med Wochenschr. 2006 Aug 25;131(34-35):1880; author

reply 1882-3. Dtsch Med Wochenschr. 2006 Aug 25;131(34-35):1881-2;

author reply 1882-3. Dtsch Med Wochenschr. 2006 Aug 25;131(34-

35):1882; author reply 1882-3. [Acute hepatitis due to kava-kava and St

John's Wort: an immune-mediated mechanism?] [Article in German]

Musch E, Chrissafidou A, Malek M. Marienhospital Bottrop, Abteilung für

Innere Medizin, Bottrop. eugen.musch HISTORY AND

CLINICAL FINDINGS: In an otherwise healthy 48-year-old female patient,

acute hepatitis with transaminase increase (GOT up to 613 U/l, GPT up to

752 U/l), inconspicuous hepatitis serology findings, negative autoantibody

status and negative virus serology was observed after a 10-week long intake

of kava-kava (1-3 x 200 mg/day) and St John's Wort (1 x 425 mg/day).

Biopsy of the liver showed lobular and portal necroinflammatory activity

without indication of cirrhosis. DIAGNOSIS: Due to these findings with

proven T-cell activity (lymphocyte typing, neopterin determination) as well as

the aetiopathology, this form of hepatitis with histological characteristics of

a

nutritive/medicinal toxic origin was classified as induced immunologic

idiosyncratic hepatitis, possibly in terms of an antibody-negative autoimmune

hepatitis. TREATMENT AND CLINICAL COURSE: Discontinuation of the

existing medication and simultaneous onset of immunosuppressive

combination therapy of cortisone, azathioprine and ursodeoxycholic acid

resulted in normalisation of the liver parameters within a period of two

months. CONCLUSION: On the one hand, it appears that simultaneous

intake of St John's Wort possibly potentiates the toxicity of kavapyrones. On

the other hand, an immune-mediated mechanism, induced by kava-kava,

cannot be completely excluded in the present case. It must be stressed that

in patients with autoimmune hepatitis, precise history of medication intake

should also be available. Publication Types: Case Reports English

Abstract PMID: 16721710 [PubMed - indexed for MEDLINE]

 

J Agric Food Chem. 2006 Apr 19;54(8):2881-90. Evaluation of the light-

sensitive cytotoxicity of Hypericum perforatum extracts, fractions, and pure

compounds. Schmitt LA, Liu Y, Murphy PA, Birt DF. The Center for

Research on Dietary Botanical Supplements, Iowa State University, Ames,

Iowa 50014, USA. Hypericum perforatum (Hp) is known for possessing

antidepressant and antiviral activities. Despite its use as an alternative to

conventional antidepressants, the identification of the cytotoxic chemicals

derived from this herb is incomplete. In this study, the cytotoxicity of Hp

extracts prepared in solvents ranging in polarity, fractions of one extract, and

purified compounds were examined in three cell lines. All extracts exhibited

significant cytotoxicity; those prepared in ethanol (no hyperforin, 3.6 microM

hypericin, and 134.6 microM flavonoids) showed between 7.7 and 77.4% cell

survival (p < 0.0001 and 0.01), whereas the chloroform and hexane extracts

(hyperforin, hypericin, and flavonoids not detected) showed approximately

9.0 (p < 0.0001) and 4.0% (p < 0.0001) survival. Light-sensitive toxicity was

observed primarily with the ethanol extracts sequentially extracted following

removal of material extracted in either chloroform or hexane. The absence

of light-sensitive toxicity with the Hp extracts suggests that the hypericins

were not playing a prominent role in the toxicity of the extracts. Publication

Types: Research Support, N.I.H., Extramural PMID: 16608204 [PubMed

- indexed for MEDLINE]

 

J Ethnopharmacol. 2004 Oct;94(2-3):345-51. Hypericum androsaemum

infusion increases tert-butyl hydroperoxide-induced mice hepatotoxicity in

vivo. Valentão P, Carvalho M, Carvalho F, Fernandes E, das Neves RP,

Pereira ML, Andrade PB, Seabra RM, Bastos ML. Department of

Pharmacognosy, University of Porto, Rua Aníbal Cunha, 4050-047,

Portugal. Increasing evidence regarding free radical generating agents

indicates that the sustained production of high levels of reactive oxygen

species (ROS) can cause hepatotoxicity. Being a short chain analog of lipid

peroxide, tert-butyl hydroperoxide (t-BHP) is metabolized into free radical

intermediates by cytochrome P450 in hepatocytes, which initiate lipid

peroxidation, glutathione depletion and cell damage. The aim of the present

study was to evaluate the putative protective effect of Hypericum

androsaemum lyophilised infusion against t-BHP-induced mice

hepatotoxicity in vivo, which has already been shown to be antioxidant in

vitro. However, the results showed that the oral pretreatment with Hypericum

androsaemum infusion (4, 20 and 100 mg/kg) for 4 days before a single

intraperitoneal dose of t-BHP (1.8 mmol/kg) potentiated the t-BHP-induced

hepatotoxicity. In fact, it was observed a potentiation in the depletion of

total

glutathione and reduced glutathione (GSH) contents and increase in

oxidised glutathione (GSSG) level. Also the histopathological evaluation of

the mice livers revealed that the infusion raised the incidence of liver lesions

induced by t-BHP. These data do not corroborate any effect of Hypericum

androsaemum infusion as hepatoprotector, but rather as a potentiator of

hepatotoxicity in the present experimental conditions. Publication Types:

Comparative Study Research Support, Non-U.S. Gov't PMID: 15325741

[PubMed - indexed for MEDLINE]

 

J Photochem Photobiol B. 1998 Sep;45(2-3):87-94. Photocytotoxic effect of

pseudohypericin versus hypericin. Vandenbogaerde AL, Kamuhabwa A,

Delaey E, Himpens BE, Merlevede WJ, de Witte PA. Laboratorium voor

Farmaceutische Biologie en Fytofarmacologie, Faculteit Farmacie, Leuven,

Belgium. Pseudohypericin and hypericin, the major photosensitizing

constituents of Hypericum perforatum, are believed to cause hypericism.

Since hypericin has been proposed as a photosensitizer for photodynamic

cancer therapy, the photocytotoxicity of its congener pseudohypericin has

been investigated. The presence of foetal calf serum (FCS) or albumin

extensively inhibits the photocytotoxic effect of pseudohypericin against

A431 tumour cells, and is associated with a large decrease in cellular uptake

of the compound. These results suggest that pseudohypericin, in contrast to

hypericin, interacts strongly with constituents of FCS, lowering its interaction

with cells. Since pseudohypericin is two to three times more abundant in

Hypericum than hypericin and the bioavailabilities of pseudohypericin and

hypericin after oral administration are similar, these results suggest that

hypericin, and not pseudohypericin, is likely to be the constituent responsible

for hypericism. Moreover, the dramatic decrease of photosensitizing activity

of pseudohypericin in the presence of serum may restrict its applicability in

clinical situations. Publication Types: Comparative Study Research

Support, Non-U.S. Gov't PMID: 9868799 [PubMed - indexed for MEDLINE]

 

J Photochem Photobiol B. 2006 Nov 1;85(2):118-30. Epub 2006 Jul 21.

Reduction in hypericin-induced phototoxicity by Hypericum perforatum

extracts and pure compounds. Schmitt LA, Liu Y, Murphy PA, Petrich JW,

Dixon PM, Birt DF. The Center for Research on Dietary Botanical

Supplements, Iowa State University, 215 MacKay Building, Ames, IA 50011-

1120, USA. Clinical evidence suggests that administration of Hypericum

perforatum (Hp) extracts containing the photo-activated hypericin

compounds may cause fewer skin photosensitization reactions than

administration of pure hypericin. This study was conducted to determine

whether the phototoxicity of hypericin in HaCaT keratinocytes could be

attenuated by H. perforatum extracts and constituents. Two extracts, when

supplemented with 20 microM hypericin: (1) an ethanol re-extraction of

residue following a chloroform extraction (denoted ethanol(-chloroform))

(3.35 microM hypericin and 124.0 microM total flavonoids); and (2) a

chloroform extract (hypericin and flavonoids not detected), showed 25% and

50% (p<0.0001) less phototoxicity than 20 microM hypericin alone. Two H.

perforatum constituents, when supplemented with 20 microM hypericin: (1)

10 microM chlorogenic acid; and (2) 0.25 microM pyropheophorbide,

exhibited 24% (p<0.05) and 40% (p<0.05) less phototoxicity than 20 microM

hypericin alone. The peroxidation of arachidonic acid was assessed as a

measure of oxidative damage by photo-activated hypericin, but this

parameter of lipid peroxidation was not influenced by the extracts or

constituents. However alpha-tocopherol, a known antioxidant also did not

influence the amount of lipid peroxidation induced in this system. These

observations indicate that hypericin combined with H. perforatum extracts or

constituents may exert less phototoxicity than pure hypericin, but possibly

not through a reduction in arachidonic acid peroxidation. Publication Types:

Research Support, N.I.H., Extramural PMID: 16859921 [PubMed - indexed

for MEDLINE]

 

Mol Nutr Food Res. 2005 Feb;49(2):131-58. Molecular mechanisms of

toxicity of important food-borne phytotoxins. Rietjens IM, Martena MJ,

Boersma MG, Spiegelenberg W, Alink GM. Division of Toxicology,

Wageningen University, Wageningen, The Netherlands.

ivonne.rietjens At present, there is an increasing interest for plant

ingredients and their use in drugs, for teas, or in food supplements. The

present review describes the nature and mechanism of action of the

phytochemicals presently receiving increased attention in the field of food

toxicology. This relates to compounds including aristolochic acids,

pyrrolizidine alkaloids, beta-carotene, coumarin, the alkenylbenzenes

safrole, methyleugenol and estragole, ephedrine alkaloids and synephrine,

kavalactones, anisatin, St. John's wort ingredients, cyanogenic glycosides,

solanine and chaconine, thujone, and glycyrrhizinic acid. It can be concluded

that several of these phytotoxins cause concern, because of their

bioactivation to reactive alkylating intermediates that are able to react with

cellular macromolecules causing cellular toxicity, and, upon their reaction

with DNA, genotoxicity resulting in tumors. Another group of the phytotoxins

presented is active without the requirement for bioactivation and, in most

cases, these compounds appear to act as neurotoxins interacting with one

of the neurotransmitter systems. Altogether, the examples presented

illustrate that natural does not equal safe and that in modern society adverse

health effects, upon either acute or chronic exposure to phytochemicals, can

occur as a result of use of plant- or herb-based foods, teas, or other

extracts. Publication Types: Review PMID: 15635687 [PubMed -

indexed for MEDLINE]

 

Photochem Photobiol. 2004 Nov-Dec;80(3):583-6. Phototoxicity in human

lens epithelial cells promoted by St. John's Wort. He YY, Chignell CF, Miller

DS, Andley UP, Roberts JE. Laboratory of Chemistry and Pharmacology,

National Institute of Environmental Health Sciences, Research Triangle

Park, NC 10023, USA. St. John's Wort (SJW), an over-the-counter

antidepressant, contains hypericin, which absorbs light in the UV and visible

ranges and is phototoxic to skin. To determine if it also could be phototoxic

to the eye, we exposed human lens epithelial cells to 0.1-10 microM

hypericin and irradiated them with 4 J/cm2 UV-A or 0.9 J/cm2 visible light.

Neither hypericin exposure alone nor light exposure alone reduced cell

viability. In contrast, cells exposed to hypericin in combination with UV-A or

visible light underwent necrosis and apoptosis. The ocular antioxidants lutein

and N-acetyl cysteine did not prevent damage. Thus, ingested SJW is

potentially phototoxic to the eye and could contribute to early

cataractogenesis. Precautions should be taken to protect the eye from

intense sunlight while taking SJW. PMID: 15623347 [PubMed - indexed for

MEDLINE]

 

Phytomedicine. 2001 Jul;8(4):306-9. Role of flavonoids in controlling the

phototoxicity of Hypericum perforatum extracts. Wilhelm KP, Biel S, Siegers

CP. proDERM Institute for Applied Dermatological Research GmbH,

Schenefeld/Hamburg, Germany. Hypericum perforatum extracts are used

mainly as oral antidepressants. Depending on source the extracts contain

various amounts of phenylpropanes, flavonol derivates, biflavones,

proathocyanidines, xanthones, phloroglucinoles, some amino acids,

naphtodianthrones (hypericines) and essential oil constituents. The

therapeutic use of Hypericum perforatum extracts however is limited by their

phototoxic potential. It was the aim of the present study to investigate the

phototoxic potential of 3 Hypericum perforatum extracts from different

sources as well as some of its main constituents. In order to systematically

study the phototoxic potential we established a modified neutral red assay

utilizing an immortalized human keratinocyte cell line (HaCaT cells) as

substrate and UVA irradiation. This modified neutral red assay was found to

be a simple and reliable method for detecting phototoxic effects of reference

agents and plant extracts. The validity of this method was demonstrated with

known phototoxic compounds like chloropromazine and psoralenes like 5-

MOP. Hypericum perforatum extracts demonstrated cytotoxicity and

photocytotoxicity in a dose and UVA-dose dependent manner. Hypericine

itself also evoked severe phototoxic effects and was thus identified as the

main phototoxic constituent. Among the tested flavonoids quercitrin was

found to be cytotoxic, while rutin unexpectedly demonstrated phototoxicity

whereas quercitrin was effective to control the phototoxic activity of

Hypericum perforatum extracts. PMID: 11515722 [PubMed - indexed for

MEDLINE]

 

Planta Med. 2005 Nov;71(11):1030-5. The lipophilic extract of Hypericum

perforatum exerts sicytotoxic activity against T24 and NBT-II urinary bladder

tumor cells. Skalkos D, Stavropoulos NE, Tsimaris I, Gioti E, Stalikas CD,

Nseyo UO, Ioachim E, Agnantis NJ. Department of Material Sciences &

Engineering, University of Ioannina, Greece. dskalkos Hypericum

perforatum L. (St. John's wort) is a medicinal plant used for many

pathologies, especially for the treatment of mild to moderate depression. In

the present study we have investigated the cytotoxic activity of the locally

collected (Epirus region) Hypericum perforatum L. against cultured T24 and

NBT-II bladder cancer cell lines. The lipophilic extract of the herb, prepared

using petroleum ether, induced apoptosis displaying LC(50) values at

concentrations as low as 4 and 5 microg/mL. A fraction of this extract

displayed 60 % cell growth inhibition at a concentration of 0.95 microg/mL.

Evaluating the importance of various biologically active components of the

extract, it was found that hypericins (hypericin, pseudohypericin, etc.) were

identified only in the methanolic (lipophobic) extract of the herb, and not in

the active lipophilic extract. In addition, hyperforin concentrations in the

lipophilic extract and its most active fraction, were 0.94 microg/mL, and 0.17

microg/mL, respectively, while the active cytotoxic concentration of pure

hyperforin appeared in the range of 1.8 microg/mL - 5.0 microg/mL.

Therefore, pure hyperforin does not seem to contribute significantly to the

cytotoxicity activity. Chlorophylls were identified in low, not significantly

different, concentrations in all extracts and fractions and were not correlated

to the biological activity. Owing to the combination of significant cytotoxic

activity, natural abundance and low toxicity, the lipophilic extract of

Hypericum perforatum holds the promise of being an interesting, new,

antiproliferative agent against bladder cancer that deserves further

investigation. Publication Types: Research Support, Non-U.S. Gov't

PMID: 16320204 [PubMed - indexed for MEDLINE]

 

Psychopharmacology (Berl). 2001 Feb;153(4):402-14. St. John's wort

(Hypericum perforatum): a review of the current pharmacological,

toxicological, and clinical literature. Greeson JM, Sanford B, Monti DA.

Center for Integrative Medicine, Thomas Jefferson University Hospital,

Jefferson Medical College, Philadelphia, PA 19107-6799, USA.

jeffrey.m.greeson RATIONALE: St. John's wort (Hypericum

perforatum) has recently gained popularity as an alternative treatment for

mild to moderate depression. Given the current widespread use of this

herbal remedy, it is important for medical professionals to understand the

potential pharmacological pathways through which Hypericum may exert an

antidepressant effect. OBJECTIVES: (1) To review the current

pharmacological, toxicological, and clinical literature available on Hypericum,

and (2) to provide a synthesis of this information into a form that may be

easily used by health care providers. METHOD: A comprehensive review of

the recent scientific literature (January 1990-March 2000) was performed

using the following electronic databases and reference publications:

MEDLINE, The Cochrane Library, HealthSTAR, Current Contents (all

editions), European Scientific Cooperative on Phytotherapy monographs,

German Commission E monographs, and the Physicians' Desk Reference

for Herbal Medicines, 1st edition. RESULTS: One hundred and seven (107)

publications in the English language and three publications in German were

included in the review. Collectively, the data suggest that therapeutic

preparations of Hypericum extract appear to exert potentially significant

pharmacological activity within several neurochemical systems believed to

be implicated in the pathophysiology of depression. However, little

information exists regarding the safety of Hypericum, including potential

herb-drug interactions. CONCLUSIONS: Additional research on the

pharmacological and biochemical activity of Hypericum and its several

bioactive constituents is necessary to further elucidate the mode(s) of

antidepressant action. Given what is currently known and unknown about

the biological properties of Hypericum, those who choose to use this herb

should be closely monitored by a physician. Publication Types: Review

PMID: 11243487 [PubMed - indexed for MEDLINE]

 

Redox Rep. 2006;11(1):3-8. Effect of benzophenones from Hypericum

annulatum on carbon tetrachloride-induced toxicity in freshly isolated rat

hepatocytes. Mitcheva M, Kondeva M, Vitcheva V, Nedialkov P, Kitanov G.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Medical

University - Sofia, Sofia, Bulgaria. Five benzophenones and a xanthone,

isolated from Hypericum annulatum Moris, were investigated for their

protective effect against carbon tetrachloride toxicity in isolated rat

hepatocytes. The benzophenones and the xanthone gentisein were

administered alone (100 microM) and in combination with CCl4 (86 microM).

CCl4 undergoes dehalogenation in the liver endoplasmic reticulum. This

process leads to trichlormethyl radical (*CCl3) formation, initiation of lipid

peroxidation, and measurable toxic effects on the hepatocytes. The levels of

thiobarbituric acid reactive substances (TBARS) were assayed as an index

of lipid peroxidation (LPO). Lactate dehydrogenase (LDH) leakage, cell

viability and reduced glutathione (GSH) depletion were used as signs of

cytotoxicity. CCl4 significantly decreased hepatocyte viability, GSH level and

increased TBARS level and LDH leakage as compared to the control. Our

data indicate that 2,3',5',6-tetrahydroxy-4-methoxybenzophenone, 2-O-

alpha-L-arabinofuranosyl-3',5',6-trihydroxy-4-methoxybenzophenone and 2-

O-alpha-L-3'-acetylarabinofuranosyl-3',5',6-trihydroxy-4-methoxybenzoph

enone showed weaker toxic effects compared to CCl4 and in combination

showed statistically significant protection against the toxic agent. PMID:

16571270 [PubMed - indexed for MEDLINE]

 

Rev Assoc Med Bras. 2005 Jul-Aug;51(4):206-8. Epub 2005 Aug 24.

[Evaluation of Hypericum perforatum toxicity when administered to pregnant

rats] [Article in Portuguese] Borges LV, Carmo JC, Peters VM, Las Casas

L, Guerra Mde O. Centro de Biologia da Reprodução, Universidade Federal

de Juiz de Fora e ne farmácia de manipulação Las Casas, Juiz de Fora,

Minas Gerais (MG), Brazil. BACKGROUND: Saint John's wort (Hypericum

perforatum) is a medicinal plant used in the treatment of depression and

other psychiatric disorders. OBJECTIVE: In the present paper, the toxicity of

H. perforatum administered to female rats during organogenesis (9th to 15th

day of pregnancy) was evaluated. METHODS: Thirty inseminated Wistar

rats were randomly distributed into Control and Treated groups, which

received by gavage, respectively, 0.5 ml of saline and 36 mg/Kg body weight

of Jarsin dried extract diluted into 0.5 ml of saline. Maternal toxicity was

evaluated by means of: water and food intake, body weight, piloerection,

walking activity, diarrhea and death. Animals were killed on the 21st day of

pregnancy, when kidneys, liver and ovaries were weighed. Implantation and

reabsorption indices were calculated, as well as the average number of

fetuses per mother. RESULTS: Clinical signs of maternal toxicity were not

observed and none of the variables analyzed showed statistically significant

differences. CONCLUSION: At the dose administered in the experimental

model used, H. perforatum does not seem to be toxic to the mother.

Publication Types: English Abstract Research Support, Non-U.S. Gov't

PMID: 16127580 [PubMed - indexed for MEDLINE]

 

Toxicol Appl Pharmacol. 2004 Nov 1;200(3):201-5. Toxicity of Hypericum

perforatum (St. John's wort) administered during pregnancy and lactation in

rats. Gregoretti B, Stebel M, Candussio L, Crivellato E, Bartoli F, Decorti G.

Department of Biomedical Sciences, University of Trieste, 34127 Trieste,

Italy. The popularity of St. John's wort (Hypericum perforatum) for the

treatment of depression is increasing and, in recent years, concerns about

its use during pregnancy and breastfeeding have emerged. The purpose of

this study was to investigate, in Wistar rats, the effects of a treatment with

hypericum administered prenatally and during breastfeeding (from 2 weeks

before mating to 21 days after delivery). Two doses of the extract were

chosen, 100 mg/kg per day, which, based on surface area, is comparable to

the dose administered to humans, and 1000 mg/kg per day. A microscopical

analysis of livers, kidneys, hearts, lungs, brains, and small bowels was

performed. A severe damage was observed in the livers and kidneys of

animals euthanized postnatally on days 0 and 21. The lesions were more

severe with the higher dose and in animals that were breastfed for 21 days;

however, an important renal and hepatic damage was evident also with the

dose of 100 mg/kg per day. In addition, similar serious hepatic and renal

lesions were evident also in animals that were exposed to hypericum only

during breastfeeding. In particular, a focal hepatic damage, with

vacuolization, lobular fibrosis, and disorganization of hepatic arrays was

evident; in the kidney, a reduction in glomerular size, disappearance of

Bowman's space, and hyaline tubular degeneration were found. The results

obtained in this study indicate that further, appropriate histological studies

should be performed in other animal species to better evaluate the safety of

hypericum extracts taken during pregnancy and breastfeeding. Publication

Types: Research Support, Non-U.S. Gov't PMID: 15504456 [PubMed -

indexed for MEDLINE]

 

Toxicol Lett. 1982 Feb;10(2-3):183-8. Consumption of poisonous plants

(Senecio jacobaea, Symphytum officinale, Pteridium aquilinum, Hypericum

perforatum) by rats: chronic toxicity, mineral metabolism, and hepatic drug-

metabolizing enzymes. Garrett BJ, Cheeke PR, Miranda CL, Goeger DE,

Buhler DR. Effect of dietary tancy ragwort (Senecio jacobaea), comfrey

(Symphytum officinale), bracken (Pteridium aquilinum) and alfalfa (Medicago

sativa) on hepatic drug-metabolizing enzymes in rats were measured. Tansy

ragwort and bracken increased (P less than 0.05) the activity of glutathione

transferase and epoxide hydrolase. Comfrey and alfalfa increased (P less

than 0.05) the activity of aminopyrine N-demethylase. Feeding bracken or

St. John's wort (Hypericum perforatum) in conjunction with tansy ragwort did

not influence chronic toxicity of tansy ragwort as assessed by rat survival

time. Dietary tansy ragwort resulted in increased (P less than 0.05) hepatic

copper levels; the other plants did not affect copper levels. The results do

not suggest any major interaction in the toxicity of tansy ragwort with

bracken or St. John's wort. Publication Types: Research Support, Non-

U.S. Gov't Research Support, U.S. Gov't, P.H.S. PMID: 7080084

[PubMed - indexed for MEDLINE]

 

Toxicol Lett. 2005 Sep 15;158(3):220-4. Photogenotoxicity of hypericin in

HaCaT keratinocytes: implications for St. John's Wort supplements and high

dose UVA-1 therapy. Traynor NJ, Beattie PE, Ibbotson SH, Moseley H,

Ferguson J, Woods JA. Photobiology Unit, Department of Dermatology,

Ninewells Hospital and Medical School, University of Dundee, Scotland,

Dundee DD1 9SY, UK. Extract of St. John's Wort (Hypericum perforatum) is

commonly used as natural remedy for treatment of mild to moderate

depression. However, it contains a powerful photoactive component,

hypericin, which can cause a severe photodermatitis when eaten by grazing

animals (hypericism). In humans, there is evidence that supplementation

with St. John's Wort can reduce the minimal erythemal dose (MED) in

patients undergoing high dose UVA-1 phototherapy. This is a recent

development in phototherapy where the most erythemogenic parts of the

UVA spectrum are filtered out, allowing delivery of higher doses of the

longer wavelengths of UVA. Although current published evidence suggests

that the plasma levels of hypericin are unlikely to cause clinical

phototoxicity,

it has been established that photoactive compounds can cause DNA

damage at sub-toxic and sub-erythemal doses, the effects of which might

not be apparent for many years after the event. The present study used

HaCaT keratinocytes to investigate the photoclastogenic ability of hypericin

on irradiation with UVA. The results show that although the combination of

hypericin and UVA light increased the genotoxic burden, when all factors are

taken into account, the risk of significant photogenotoxic damage incurred

by the combination of Hypericum extracts and UVA phototherapy may be

low in the majority of individuals. Publication Types: Research Support,

Non-U.S. Gov't PMID: 15890476 [PubMed - indexed for MEDLINE]

 

Best regards,

 

1 Esker Lawns, Lucan, Dublin, Ireland

Tel: (H): +353-(0);

VOIP Number: +353-1482-7068;

Tel: (M): +353-(0)

 

 

 

" Man who says it can't be done should not interrupt woman doing it " -

Chinese Proverb

 

 

 

[Guest guest]

While I doubt Hypericum is hepatotoxic, one should be wary of making that

determination with such reasoning.

 

1. I doubt any careful analysis has been to either prove or disprove any

relationship between use of hypericum and liver damage. Just because something

has not been reported yet does not mean it is not occurring. The vast majority

of herb users do not inform their MDs that they are using them, so other sources

of liver damage would be suspected first. Even if a person had liver damage,

the prevailing popular, yet ludicrous, view that herbs are always safe, might

prevent them from even considering that it might be important to mention it to

their MD.

 

2. Most hypericum on the market contains very little hypericin and products that

do are often taken at so low a dosage as to be both safe and ineffective. dozens

of patients over the years have told me things like they were relived of their

depression after their first does of hypericum or that they take it occasionally

to treat depression when it arises. Hypericum does not work in this fashion, so

any such reports are actually reports of a placebo effect, which is extremely

common with depressed patients.

 

Long cultural use of an herb does not prove its safety as traditional peoples

had no way of correlating long term damage with the use of specific substances.

All reliable indications of toxicity in the classical chinese materia medica are

related to short term use with very obvious side-effects. While I do not think

herbs should have to be proven effective to be sold (though they should be

proven effective if someone wants to claim they are—either manufacturer or

practitioner), they probably should be proven safe before they are made

available OTC. Or at the very least, all products that have not been proven safe

should have a caveat emptor label to that effect on them.

 

 

-------------- Original message ----------------------

" " <

> Hi Bill, & All,

>

> Re: Photo-urticaria, Bill Schoenbart wrote:

> > Hypericum isn't hepatotoxic. Millions of doses are taken of Saint Johns

> > Wort every year with no sign of liver damage. Did you mean to say

> > something else? Bill

 

 

 

 

[Guest guest]

For that matter you can say that about every herb and suspected foods --

remember toxicity is in the dose. Forgive me and I say this with the greatest

respect, but personally I'm fed up with the uninformed widespread paranoia about

herbs among health practitioners (who should know better but are too often

taught by others passing down information without the golden ingredient which is

personal experience). At this point we have a more reliable bass of historical

evidence concerning the safety of herbs then scientific studies. It will

probably be that way for the unforseeable future because really the best

research could only be generated by an experienced practical herbalist -- the

two don't often come together.

 

So if one wants to invalidate the entire materia medica with the thesis that

" Long cultural use of an herb does not prove its safety as traditional peoples

had no way of correlating long term damage with the use of specific substances "

we might as well pursue with more vigor the job of elimination that herbal

uninformed regulating authorities are trying to pursue.

 

Now to the specific points in question. St johnswort is not a long term

treatment type of herb. It has cooling properties making it somewhat

contraindicated for cold conditions. However I've found that the humoral

application of the wrong herb in small chronic doses irregardless of the humoral

predisposition has little effect. Antibiotics are also cold but they are given

in high dose. The recommended dose of St Johnswort in Western herbalism is

smaller than a minimum TCM dose of 9 grams per day. I've often sited Western

herbalists for using too low a dose. At the over the counter dose ranges it is

remarkably safe. This is not to say that with the increased use of herbs we can

expect idosyncratic reactions but again that has to be applied with the risk

versus benefit ration applied to all drugs and you know what? --- that's where

herbs win out.

 

I repeat that with increasing popularity and use by the mainstream there is

increased risk. If a Chinese manufacturer substituted the wrong species of

aristolochia and someone suffered for it, its extremely unfortunate but this

kind of thing is rampant in the medical industry and it is tolerated because

there is a risk versus benefit ratio applied.

 

We cannot have a " no risk " with anything, including any food -- so we operate at

a disadvantage but we need to continue to vigorously defend the safety of the

herbs we use based on evidence and historic usage or we all will lose.

 

Michael tierra

 

 

 

On Behalf Of

Wednesday, July 11, 2007 11:09 AM

 

Re: Hypericum is a photosensitising & toxic plant

 

While I doubt Hypericum is hepatotoxic, one should be wary of making that

determination with such reasoning.

 

1. I doubt any careful analysis has been to either prove or disprove any

relationship between use of hypericum and liver damage. Just because something

has not been reported yet does not mean it is not occurring. The vast majority

of herb users do not inform their MDs that they are using them, so other sources

of liver damage would be suspected first. Even if a person had liver damage,

the prevailing popular, yet ludicrous, view that herbs are always safe, might

prevent them from even considering that it might be important to mention it to

their MD.

 

2. Most hypericum on the market contains very little hypericin and products that

do are often taken at so low a dosage as to be both safe and ineffective. dozens

of patients over the years have told me things like they were relived of their

depression after their first does of hypericum or that they take it occasionally

to treat depression when it arises. Hypericum does not work in this fashion, so

any such reports are actually reports of a placebo effect, which is extremely

common with depressed patients.

 

All reliable indications of toxicity in the classical chinese materia medica are

related to short term use with very obvious side-effects. While I do not think

herbs should have to be proven effective to be sold (though they should be

proven effective if someone wants to claim they areâ€â€either manufacturer

or practitioner), they probably should be proven safe before they are made

available OTC. Or at the very least, all products that have not been proven safe

should have a caveat emptor label to that effect on them.

 

 

-------------- Original message ----------------------

" " <

> Hi Bill, & All,

>

> Re: Photo-urticaria, Bill Schoenbart wrote:

> > Hypericum isn't hepatotoxic. Millions of doses are taken of Saint Johns

> > Wort every year with no sign of liver damage. Did you mean to say

> > something else? Bill

 

 

 

 

[Guest guest]

Numerous clinical trials have been done on Hypericum. Most studies

used products that were standardized to hypericin content. No trials

have reported adverse hepatic effects. Believe me, if it had

happened, it would have been in the headlines.

 

Hypericum is quite safe. The only danger it poses is when it is

taken with drugs. The Hypericum itself isn't dangerous, but it

induces the cytochrome P450 enzyme, which means that any drugs taken

along with Hypericum will clear the body faster than normal. That's

why women who take Hypericum with birth control can get pregnant, or

why somebody may not have the desired level of any drug in the

system.

 

Although the standard for depression is to wait 5 weeks for it to

take effect, Hypericum DOES affect mood much faster. I have

experienced that many times. It can have an immediate effect. People

suffering depression do need a longer time to feel the effect,

though.

 

- Bill

 

 

, wrote:

>

> While I doubt Hypericum is hepatotoxic, one should be wary of

making that determination with such reasoning.

>

> 1. I doubt any careful analysis has been to either prove or

disprove any relationship between use of hypericum and liver damage.

Just because something has not been reported yet does not mean it is

not occurring. The vast majority of herb users do not inform their

MDs that they are using them, so other sources of liver damage would

be suspected first. Even if a person had liver damage, the

prevailing popular, yet ludicrous, view that herbs are always safe,

might prevent them from even considering that it might be important

to mention it to their MD.

>

> 2. Most hypericum on the market contains very little hypericin and

products that do are often taken at so low a dosage as to be both

safe and ineffective. dozens of patients over the years have told me

things like they were relived of their depression after their first

does of hypericum or that they take it occasionally to treat

depression when it arises. Hypericum does not work in this fashion,

so any such reports are actually reports of a placebo effect, which

is extremely common with depressed patients.

>

> Long cultural use of an herb does not prove its safety as

traditional peoples had no way of correlating long term damage with

the use of specific substances. All reliable indications of toxicity

in the classical chinese materia medica are related to short term

use with very obvious side-effects. While I do not think herbs

should have to be proven effective to be sold (though they should be

proven effective if someone wants to claim they are†" either

manufacturer or practitioner), they probably should be proven safe

before they are made available OTC. Or at the very least, all

products that have not been proven safe should have a caveat emptor

label to that effect on them.

>

>

> -------------- Original message ----------------------

> " " <

> > Hi Bill, & All,

> >

> > Re: Photo-urticaria, Bill Schoenbart wrote:

> > > Hypericum isn't hepatotoxic. Millions of doses are taken of

Saint Johns

> > > Wort every year with no sign of liver damage. Did you mean to

say

> > > something else? Bill

>

>

>

>

[Guest guest]

The specific indication for hypericum is for nerve pain. It is very specific for

cocygeal (sp) pain. I had a very memorable patient who had chronic-acute pain of

the coccyx. I did a lot of acupuncture and other herbal treatments for this

condition, though this was many years ago and I think my acupuncture skill has

improved a lot these days and if i were to see someone like that patient again

today, i probably could do better. However, I looked up hypericum in Boericke's

Materia Medica (a really important book not only for homeopathy but for herbal

therapy, with an incredible array of psycho-physiological indicates for each

herb) and it said it was specific for pain of the coccyx. I gave her the mother

tincture about 30 drops 3 times daily and within three days the pain was

completely gone. Nerve pain, nerve damage, pains such as smashing a finger with

a hammer are all very responsive to hypericum. Its because of its traditional

benefit for the nervous system that hypericum has become popular for depression.

Think of it as an herb that relieves blood and qi stagnation and cools heat

(antiinflammatory). Its one of the great herbs of the world.

 

It has a traditional use in Chinese medicine. The whole herb is classified as

sweet and slightly bitter, cool, antipyretic, anti-inflammatory, antibiotic,

diuretic, dispels stagnant blood, anti-swelling. It is used for acute and

chronic hepatitis, early stage of hepatic cirrhosis, actue conjunctivitis,

tonsilities, appendicitis/ The Chinese dose is 15 to 60 gm prepared as a

decoction. Externally it is used for boils, furuncles, pyodermas, herpes zoster,

snake bites, traumatic injury. The fresh herb is mashed and topically applied.

(from Chinese Medicinal Herbs of hong Kong vol 2 ( a great series of books that

describes many herbs commonly used by Western herbalists that are locally used

in Chinese folk medicine).

 

Michael Tierra

www.planetherbs.cm

 

_____

 

 

On Behalf Of bill_schoenbart

Wednesday, July 11, 2007 5:24 PM

 

Re: Hypericum is a photosensitising & toxic plant

 

 

 

Numerous clinical trials have been done on Hypericum. Most studies

used products that were standardized to hypericin content. No trials

have reported adverse hepatic effects. Believe me, if it had

happened, it would have been in the headlines.

 

Hypericum is quite safe. The only danger it poses is when it is

taken with drugs. The Hypericum itself isn't dangerous, but it

induces the cytochrome P450 enzyme, which means that any drugs taken

along with Hypericum will clear the body faster than normal. That's

why women who take Hypericum with birth control can get pregnant, or

why somebody may not have the desired level of any drug in the

system.

 

Although the standard for depression is to wait 5 weeks for it to

take effect, Hypericum DOES affect mood much faster. I have

experienced that many times. It can have an immediate effect. People

suffering depression do need a longer time to feel the effect,

though.

 

- Bill

 

@ <%40>

, wrote:

>

> While I doubt Hypericum is hepatotoxic, one should be wary of

making that determination with such reasoning.

>

> 1. I doubt any careful analysis has been to either prove or

disprove any relationship between use of hypericum and liver damage.

Just because something has not been reported yet does not mean it is

not occurring. The vast majority of herb users do not inform their

MDs that they are using them, so other sources of liver damage would

be suspected first. Even if a person had liver damage, the

prevailing popular, yet ludicrous, view that herbs are always safe,

might prevent them from even considering that it might be important

to mention it to their MD.

>

> 2. Most hypericum on the market contains very little hypericin and

products that do are often taken at so low a dosage as to be both

safe and ineffective. dozens of patients over the years have told me

things like they were relived of their depression after their first

does of hypericum or that they take it occasionally to treat

depression when it arises. Hypericum does not work in this fashion,

so any such reports are actually reports of a placebo effect, which

is extremely common with depressed patients.

>

> Long cultural use of an herb does not prove its safety as

traditional peoples had no way of correlating long term damage with

the use of specific substances. All reliable indications of toxicity

in the classical chinese materia medica are related to short term

use with very obvious side-effects. While I do not think herbs

should have to be proven effective to be sold (though they should be

proven effective if someone wants to claim they are†" either

manufacturer or practitioner), they probably should be proven safe

before they are made available OTC. Or at the very least, all

products that have not been proven safe should have a caveat emptor

label to that effect on them.

>

>

> -------------- Original message ----------------------

> " " <

> > Hi Bill, & All,

> >

> > Re: Photo-urticaria, Bill Schoenbart wrote:

> > > Hypericum isn't hepatotoxic. Millions of doses are taken of

Saint Johns

> > > Wort every year with no sign of liver damage. Did you mean to

say

> > > something else? Bill

>

>

>

>

[Guest guest]

Phil,

 

At a brief glance, I can tell you that the article linked below has a

serious error. It claims that Hypericum contains toxic pyrrolizidine

alkaloids. It doesn't. It also says that Hypericum's common name is

Heliotrope. It isn't.

 

- Bill

 

 

, " "

< wrote:

>

Hypericum (like basic essentials for life, such as air, water and

common

> salt) is no exception. For example, see:

> http://vet.purdue.edu/depts/addl/toxic/plant38.htm

[Guest guest]

Regarding nerve pain, I have found Hypericum to be very effective at

alleviating pain after dental work. It is very fast-acting.

 

- Bill

 

 

 

, " Michael Tierra "

<mtierra wrote:

>

> The specific indication for hypericum is for nerve pain.

[Guest guest]

When looking at toxicity studies in animal reports, it is important to

remember that cattle eat POUNDS of Hypericum. It really can't be

compared to human usage.

 

- Bill

 

 

 

> Bill, you are correct - Hypericum usually is NOT classed as a

hepatoxin, but

> as a photosensitising agent. It is, however, classed as a toxic

plant by some

> authorities.

>

[Guest guest]

Posted by: " bill_schoenbart " _plantmed2 _

(plantmed2?Subject=

Re:%20Hypericum%20is%20a%20photosensitising%20 & %20toxic%20plant)

_bill_schoenbart _ (http://profiles./bill_schoenbart)

Wed Jul 11, 2007 11:05 pm (PST)

Phil,

 

At a brief glance, I can tell you that the article linked below has a

serious error. It claims that Hypericum contains toxic pyrrolizidine

alkaloids. It doesn't. It also says that Hypericum's common name is

Heliotrope. It isn't.

 

- Bill

 

 

 

The article with the misinformation Bill mentioned is

_http://www.ivis.org/special_books/knight/chap4b/ivis.pdf_

(http://www.ivis.org/special_books/knight/chap4b/ivis.pdf)

 

 

Karen S. Vaughan, L.Ac., MSTOM

Licensed Acupuncturist, and Herbalist

Creationsgarden1

253 Garfield Place

Brooklyn, NY 11215

 

(718) 622-6755

 

 

 

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