Ayurveda

1. Natural Product Radiance, Vol. 8(1), 2009, pp.55-63 General Article
Phytotherapy–Safety aspects
Annie Shirwaikar1*, Renu Verma1, Richard Lobo1 and Arun Shirwaikar2
1
Department of Pharmacognosy, Manipal College of Pharmaceutical Sciences
Manipal University, Manipal-576 104, Karnataka, India
2
Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences
Manipal University, Manipal
*Correspondent author, E-mail: annieshirwaikar@yahoo.com
Received 14 January 2008; Accepted 30 July 2008
Abstract prohibited in unlicensed medicinal
Plants have been used since ancient times as medicines for the treatment of a range of products. Other concerns, particularly
diseases. In spite of the great advances observed in modern medicine in recent decades, plants still interactions with conventional medicines,
make an important contribution to health care. According to the World Health Organization are the consequence of using conventional
(WHO), because of poverty and lack of access to modern medicine, about 65-80% of the world’s medicines and herbal products
population that are living in developing countries depend essentially on plants for primary health
simultaneously and are of no surprise
care. Phytotherapeutic agents are herbal preparations consisting of complex mixtures of one or
more plants which contain active ingredients, plant parts or plant material in the crude or processed from a scientific viewpoint. Interactions,
state. The data existing for most plants to guarantee their quality, efficacy and safety is insufficient. particularly those with medicines, can and
The concept that herbal drugs are safe and free from side effects is not always. Plants contain do give rise to serious public health
hundreds of constituents, some of which are very toxic namely the most cytotoxic anti-cancer concerns. The potential for herb-drug
plant-derived drugs is pyrrolizidine alkaloids, etc. However, the adverse effects of phytotherapeutic
interactions has been highlighted by the
agents are less as compared with synthetic drugs. Several regulatory models for herbal medicines
are currently available including prescription drugs, over-the-counter substances, traditional recognition that the widely used herbal
medicines and dietary supplements. Harmonization and improvement in the processes of regulation remedy, St John’s Wort (Hypericum
is needed for safety aspects related to phytotherapy. perforatum Linn.), may interact with
Keywords: Herbs, Phytotherapy, Herbal safety, Toxic constituents. certain important medicines. These
IPC code; Int. cl.8— A61K 36/00 include for example HIV protease
inhibitors, oral contraceptives,
Introduction medicinal products reflect a growing cyclosporin and warfarin, leading to a loss
market, largely unregulated, where many or reduction in the therapeutic effect of
Phytotherapeutic agents are
of the safety concerns arise due to lack of these prescribed medicines4,5.
normally marketed as standardized
effective quality controls. Other serious Compared with well-defined
preparations in the form of liquid, solid,
quality related safety problems include the synthetic drugs, herbal medicines exhibit
or viscous preparations and extracts. They
deliberate addition of prescription some marked differences: The active
are prepared by maceration, percolation
medicines and toxic heavy metals to herbal principles of herbal drugs are frequently
or distillation (volatile oils). Solid or
products1-3. unknown so that standardization, stability
extracts are prepared by evaporation of
Increased usage and awareness of and quality control, though feasible, may
the solvents used in the process of
potential safety concerns have identified not be easy. Also the availability and quality
extraction of the raw material.
hitherto unknown safety problems of raw materials are frequently
Phytotherapeutic agents are often
associated with some traditional herbal problematic and well-controlled double-
administered in a highly concentrated
products. Serious liver toxicity associated blind clinical and toxicological studies to
form so as to improve their therapeutic
with the use of Kava-kava (Piper prove their efficacy and safety are rare.
efficacy. However, some secondary
methysticum G. Forst.) has been Though the occurrence of undesirable side
metabolites present in the plants may
reported recently and it has been advised effects seems to be less frequent with
produce undesirable side effects. The
that the use of Kava-kava should be herbal medicines, well-controlled
safety problems emerging with herbal
Vol 8(1) January-February 2009 55

2. General Article
randomized clinical trials have revealed hepatotoxicity, may well have been 2. Intrinsically toxic
that they may exist 6-8. overlooked by previous generations and phytoconstituents
Therefore, there is an urgent it is these types of toxicity that are of most In many cases, the patient may
need for the public to have an concern when assessing the safety of be exposed to herbal ingredients which
understanding of the risks posed by herbal remedies11,12. are potentially toxic and possess
phytotherapy and to ensure that such constituents that may cause adverse drug
products are used judiciously. This paper Excessive ingestion: Excessive doses of reactions. Very often the constituents
attempts to highlight the safety aspects that Ginseng have been reported to cause responsible for toxicity are unknown
should be taken into consideration in agitation, insomnia and raised blood (Table 1). Given below are some
phytotherapy. The safety concerns mainly pressure and these have been referred to identified common examples of
fall into following five main categories: as abuse of the remedy. Side effects intrinsically toxic phytoconstituents.
including mastalgia and vaginal bleeding
1. Self-administration/ have been reported for ginseng following Apiole: The irritant principle present in
medication the ingestion of recommended doses. the volatile oil of parsley (Petroselinum
Self-administration of any Similarly excessive ingestion of Liquorice crispum) is found responsible for its
therapy in preference to conventional has resulted in typical corticosteroid-type abortifacient action. Apiole is also
13,14
treatment may delay a patient seeking side effects of oedema and hypertension . hepatotoxic and liver damage has been
qualified advice, or cause a patient to documented as a result of excessive
abandon conventional treatment without Hypersensitivity reactions: ingestion of parsley, far exceeding normal
first seeking appropriate advice. Toxicity Sesquiterpene lactones are known to dietary consumption over a prolonged
due to herbal drugs can also be due to possess allergenic properties. They occur period16.
insufficient knowledge about the predominantly in herbs of the Asteraceae H C O 3 CH
constituents and the dose of the drug. The family and hypersensitivity reactions have
3
safety of herbal medicinal products is of been reported for Chamomile and other
NH 2
particular importance as most of these plants of this family. Cross-sensitivity to O O CH
products are self-prescribed and are used other members of this family is well 3
O
to treat minor and often chronic recognized. The sesquiterpene lactones
conditions. Recent research highlights the present in Feverfew are considered to be Apiole
fact that patients are reluctant to tell their the active principles in the herb. It is β -Asarone: Calamus rhizome oil
doctors that they are taking herbal unknown whether documented side contains β-asarone as the major
products and thus it is probable that effects for Feverfew, such as mouth ulcers component, which has been shown to be
adverse reactions to herbal products are and swollen tongue, are also attributable carcinogenic in animal studies. Many
under-reported9,10. to this constituents15. other culinary herbs contain low levels of
The extensive traditional use of β-asarone in their volatile oils and
plants as medicines has enabled those Phototoxic reactions: Furanocoumarins, therefore, the level of β-asarone permitted
medicines with acute and obvious signs compounds known to cause phototoxic in foods as flavouring is restricted16.
of toxicity to be well recognized and their reactions, are constituents of Parsley OCH
3
use avoided. However, the promise that [Petroselinum crispum (Mill.) Airy-
H CO
traditional use of a plant for perhaps many Shaw]. Excessive ingestion of Parsley has
3
CH 3
hundreds of years establishes its safety does been associated with the development of
not necessarily hold true. The more subtle photosensitive rash, which resolved once
16
and chronic forms of toxicity, such as Parsley consumption ceased . OCH
3
carcinogenicity, mutagenicity and β-Asarone
56 Natural Product Radiance

3. General Article
COOH
Estragole: Estragole is a constituent of O use and is permitted only as an ingredient
many culinary herbs but is a major of products intended for external use on
component of the oils of Fennel and Sweet unbroken skin.
NO2
basil (Ocimum basilicum Linn.). O Lectins: Lectins are plant proteins which
Estragole has been reported to be possess haemagglutinating and potent
carcinogenic in animals and the level of mitogenic properties. Both mistletoe
estragole permitted in food products as (Viscum album Linn.) and Pokeroot
flavouring is restricted16. (Phytolacca americana Linn.)
H 2C
contain lectins. Systemic exposure to
CH 3 O CH 3 Pokeroot has resulted in haematological
O
Aristolochic acid
aberrations. Mistletoe lectins may also
inhibit protein synthesis20.
Estragole CH2OCOR
Viscotoxins: Viscotoxins are low
Safrole: Animal studies involving Safrole, molecular weight constituents of
the major component of Chinese sassafras mistletoe (V. album), which possess
oil [Cinnamomum camphora cytotoxic and cardiotoxic properties. For
(Linn.) Nees & Eberm.] have shown it N
many years, mistletoe preparations have
to be hepatotoxic and carcinogenic. The Basic nucleus of pyrrolizidine alkaloids
been used in Europe for cancer
permitted level of Safrole as a flavouring treatment20. Clinical trials carried out with
in foods is 0.1mg/kg16. known to injure the liver in humans giving Iscador, a product obtained from the
rise to serious liver damage (hepatic veno- naturally fermented plant juice of
O occlusive disease). This hepatotoxicity Mistletoe, have concluded that Iscador
associated with their consumption is well may exhibit some weak antitumour effects
O documented and has been attributed to but should only be used alongside
CH 2
the pyrrolizidine alkaloid constituents18, 19. conventional therapy in the long term
Safrole Pyrrolizidine alkaloids can be divided into treatment of cancer.
Aristolochic acids: These are reported two categories based on their structure, Lignans: The hepatotoxic reactions
to occur only in the Aristolochiaceae namely those with an unsaturated nucleus reported for Chaparral (Larrea
family. They have been reported in (toxic) and those with a saturated nucleus tridentata J. M. Coult.) have
Aristolochia species and appear to (considered non-toxic). A number of been associated with its lignan
occur throughout the plant in the roots, herbs currently used in herbal remedies constituents20.
stem, herb and fruit. The Aristolochic contain pyrrolizidines; they include Life
acids are a series of substituted root (Senecio aureus Linn.), borage
nitrophenanthrene carboxylic acids. (Borago officinalis Linn.) and
Aristolochic acids have been shown to be Comfrey (Symphytum officinale
nephrotoxic, carcinogenic and Linn.). In addition to various animal CH 3
mutagenic17. studies, two cases of human hepatotoxicity
associated with the ingestion of comfrey
Pyrrolizidine alkaloids: These are have been documented. Following advice
present in a number of plant species, of the Committee on Review of Medicines
notably Crotalaria Linn. and (CRM), comfrey has been removed from CH 3
Heliotropium Linn. These alkaloids are all licensed products intended for internal Basic lignan nucleus
Vol 8(1) January-February 2009 57

4. General Article
Saponins: Pokeroot (P. americana) extremely irritant to all mucosal surfaces. the patients had consumed Apricot kernels
also contains irritant saponins which have Cyanogenic glycosides: These are as an Alternative source of amygdalin23.
produced severe gastrointestinal irritation present in the kernels of a number of
involving intense abdominal cramping fruits including Apricot, Bitter almond, Furanocoumarins: These are found
and haematemesis. Systemic exposure to Cherry, Pear and Plum seeds. Gastric predominantly in the family — Apiaceae
these saponins has resulted in hypotension hydrolysis of these compounds following (Parsley, Celery), Rutaceae (eg. Bergamot,
and tachycardia. In May 1979, the US Herb oral ingestion results in the release of Citrus species), Moraceae and Fabaceae.
Trade Association requested that all its hydrogen cyanide (HCN), which is rapidly The furanocoumarins occur as linear and
members should stop selling Pokeroot as absorbed from the upper gastrointestinal branched forms. The most commonly
a herbal beverage or food because of its tract and lead to respiratory failure. It has reported linear furanocoumarins are
toxicity. The saponins found in Pokeroot been estimated that oral doses of 50mg 8-methoxypsoralen, 5-methoxypsoralen
include phytolaccagenin and oleanolic of HCN can be fatal, equivalent to about and psoralen itself. The furanocoumarins
acid21. 50-60 Apricot kernels 22. However, are phototoxic. Severe phototoxic
variation in cyanogenic glycoside content reactions have been reported in humans
H 3C COOCH3 of the kernels could reduce or increase following the use of Bergamot oil in
the number required for a fatal reaction. topical preparations.
H
In the early 1980s a substance called In UK a patient developed severe
amygdalin, a cyanogenic glycoside, was phototoxicity during oral photo-
COOH
promoted as a natural non-toxic cure for chemotherapy with psoralen and ultraviolet
CH 3 H3C
HO cancer. Two near-fatal episodes of HCN A (PUVA) therapy after eating a large quantity
CH 3 poisoning have been recorded in which of soup made from Celery and Parsley24-26.
H 3C
HO
CH2OH
Phytolaccagenin
Prunase Benzaldehyde
Amygdalase
CH ORR′ CH OR +
H2O H2O HCN
+
CH 3 CN CN Glucose
H3C
Amygdalin Prunasin
H (Where ORR′-genitiobiose) (Where OR’-glucose)
COOH
CH 3 H3C
CH 3
HO
H3C CH 3
O CH3
Oleanolic acid
Diterpenes: The irritant properties of O O O
many diterpenes are well documented. O O O
O
Queen’s delight (Stillingia sylvatica CH 3
Linn.) contains diterpene esters which are 5-Methoxypsoralen 8-Methoxypsoralen
58 Natural Product Radiance

5. General Article
Table 1 : Some potential toxic constituents of herbal medicines decrease the pharmacological or
toxicological effects of either component.
Herbal drug Adverse effect/toxicity Toxic constituent Synergistic therapeutic effects may
complicate the dosing of long-term
Aloe Allergic reactions, headache, increase in menstrual flow Anthraquinones
medications28, 29.
Arnica Gastroenteritis, dermatitis Anethole Herbal medicines are ubiquitous;
Artichoke Allergic contact dermatitis Sesquiterpene the dearth of reports of adverse events and
lactones interactions probably reflects a
Buchu Gastrointestinal and renal irritation Pulegone combination of under-reporting and the
Capsicum Allergic alveolitis Capsaicinoids benign nature of most herbs used.
Dandelion Contact allergic reactions Quinones Experimental data in the field of
herb-drug interactions are limited, case
Elder Nausea, vomiting, diarrhoea Cyanogenic
glycosides reports scarce and case series are also rare.
This lack of data is also true of drug-drug
Garlic Nausea, vomiting, diarrhoea, contact dermatitis Sulphur containing
compound interactions; published clinical studies are
mainly case reports. Polypharmacy is
Ginkgo Gastrointestinal upset, headache Unknown
common and to the mixture physicians
Ginseng Hypertension, diarrhoea, insomnia, vaginal bleeding, do- prescribe, patients add various over-the-
skin eruption, nervousness
counter medications, vitamins, herbs and
Isapghula Flatulence, abdominal distention, intestinal obstruction do- foods. All ingested substances have the
Liquorice Hypertension, hypokelemia, weight gain Glycyrrhizin potential to interact29.
Lobelia Nausea, vomiting diarrhoea Lobeline Pharmacodynamic types of
Rhubarb Abdominal discomfort, loss of electrolytes, Anthraquinones herb-to-drug interactions are best
urine coloured red identified by analyzing the therapeutic
Senna Abdominal discomfort, loss of electrolytes, Anthraquinones effect of the herbs and drugs (Table 2).
urine coloured red Concurrent use of herbs and drugs with
St. John’s wort Allergic reactions Unknown similar therapeutic actions will
undoubtedly pose potential risk of herb-
to-drug interactions. The increase in
3. Herb interactions vitamins. The interaction may increase or treatment effect interferes with optimal
Herbal medicinal products may decrease the effectiveness and/or the side treatment outcome; the desired effect
in some cases compromise the efficacy of effects of the drugs. It may also result in a becomes more unpredictable and harder
conventional medicines, for example new side effect, that is, a side effect not to obtain with precision. The highest risk
through herb-drug interactions, herb-herb seen with the use of any one drug alone27. of clinically-significant interactions occur
interactions and herb-food interactions. The possibility of occurrence of between herbs and drugs that have
A drug interaction is an interaction a drug interaction increases with the sympathomimetic effects, cardiovascular
between a drug and another substance that number of drugs being taken by a patient. effects, diuretic effects, anti-coagulant
prevents the drug from performing as Therefore, individuals who take several effects and anti-diabetic effects. Herbs
expected. This definition applies to medications are at the great risk for with sympathomimetic effects may
interactions of drugs with other drugs interactions. Many medicinal herbs and interfere with anti-hypertensive and
(drug-drug interactions), drugs with food pharmaceutical drugs are therapeutic at anti-seizure drugs. The classic example of
(drug-food interactions) as well as drugs one dose and toxic at another. Interactions an herb with sympathomimetic effects is
with other substances like herbs or between herbs and drugs may increase or Ephedra, which contains ephedrine,
Vol 8(1) January-February 2009 59

6. General Article
Table 2 : Herb-drug interactions32
Herb Common uses Interactions with Problems which may occur
Ephedra For asthma, cough and to Cardiac glycosides, general anesthesia, Seizures, adverse cardiovascular events,
induce weight loss MAO inhibitors, decongestants, stimulants hypertension
Garlic To decrease cholesterol and Anticoagulants, Acetaminophen Enhances bleeding, increase sulfation
blood clot formation
Ginger Nausea Anticoagulants, barbiturates, antihypertensives, Enhances bleeding, CNS depression,
cardiac drugs, hypoglycemic drugs hypotension, cardiac arrhythmia, hypoglycemia
Ginseng To increase energy and Anticoagulants, stimulants, antihypertensives, Enhances bleeding, tachycardia and
reduce stress antidepressants/phenelzine, digoxin, potentiates hypertension, mania, serotonin syndrome
the effects of corticosteroids and estrogens
Liquorice Peptic ulcers and as Antihypertensives, potentiates the effects of Hypertension, hypokalemia, edema
expectorant corticosteroids
St. John’s Wort Mild depression, anxiety, Anticoagulants, antidepressants, decreases Enhances bleeding, hastens metabolic
seasonal affective disorder the effectiveness of cyclosporine, antiviral drugs, breakdown of drugs, contra-indicated for
digoxin, dextrometorphan, prolongs the effects of organ transplant recipients, nausea, vomiting,
general anesthetics, MAO inhibitors, Nefazodone headache
pseudoephedrine, norephedrine and other anti-coagulant drugs, such as warfarin, to stimulation32 and consumption of St John’s
ephedrine alkaloids. Ephedra may interact prolong the bleeding time. Herbs that Wort and aged cheese causes fatal rise in
with many other drugs and disease interfere with warfarin include Salviae blood pressure. Cuzzolin et al33 have
conditions and should always be used with miltiorrhizae (Danshen) and reported some serious reactions leading
caution in patients with hypertension, Angelica sinensis (Oliv.) Diels. The to hospitalization due to drug interaction
seizures, diabetes, thyroid conditions, etc. synergistic interaction between herbs and (Table 3)
Concomitant use of diuretic herbs and warfarin may be advantageous for the
diuretic drugs may have additive or patient as the dosage of both the herbs 4. Quality related safety
synergistic effects; hypertension may be and drugs can be reduced without issues/Contaminants
more difficult to control and/or compromising clinical effectiveness. The The patient may be at risk of
hypotensive episodes may result. The reduction in dosage will also decrease the toxicity as a result of exposure to
dosage of herbs and/or drugs must be frequency and severity of side effects of contaminants present in the herbal
adjusted to achieve optimal treatment the drugs. Optimal treatment, however, product (Table 4).
outcome. Commonly used diuretic herbs is directly dependent on careful titration
include Poria cocos, Polypori of the herb and drug, co-operation from Substitution and adulteration: Herbal
umbellata Zhu ling and Alismatis the patient and communication between medicines adulterated with other plant
orientalis (Sam.) Juzep30- 32. the physicians who prescribe the herbs and materials and even with conventional
Herbs with anti-coagulant effects drugs30, 31. medicines cause serious toxicity, e.g.
encompass herbs that have blood- Herb-food interaction and their Aristolochia was the most significant
activating and blood-stasis-removing risks have also been reported eg. Ginseng+ cause of plant toxicity in the last decade;
functions. Such herbs may interfere with tea and coffee caused GIT upset and over inadvertent exposure to Aristolochia
60 Natural Product Radiance

7. General Article
Table 3 : Serious adverse drug reaction leading to hospitalization due to
drug interaction as reported by Cuzzolin et al 33
Herbal product Concomitant drug Adverse drug reaction Possible mechanism
Green tea Contraceptives Ischemia Cardiovascular effects due to caffeine + increase in caffeine half life by hormones
Liquorice - Hypertensive crisis Suppression of rennin-angiotensin-aldosterone axis by glycyrrhetinic acid
Liquorice Contraceptives Hypertensive crisis Suppression of rennin-angiotensin-aldosterone axis by glycyrrhetinic acid+
increase in sensitivity to glycyrrhetinic acid by oestrogens
Passion flower Benzodiazepines Anaphylactic shock Hypertensive reactions to the herb
Propolis - Systemic allergy Hypertensive reactions to Propolis
Table 4 : Some adulterants and contaminants ingredients to have aerobic bacteria
present at 102-108 colony forming units
Type of adulterant and contaminants Examples per gram. Pathogenic organisms including
Botanicals (as adulterants) Ailanthus and Phytolacca leaves substituted for
Enterobacter, Enterococcus,
Belladonna Clostridium, Pseudomonas, Shigella
Xanthium leaves for Stramonium and Dandelion for and Streptococcus have been shown to
Henbane contaminate herbal ingredients. The
Microorganisms (as contaminant) Staphylococcus aureus, Escherichia coli, European Pharmacopoeia gives guidance
Salmonella, Shiegella on acceptable microbial limits34.
Microbial toxins (as contaminant) Aflatoxin, bacterial endotoxin
Fumigation agents (as contaminant) Ethylene oxide, Methyl bromide, Phosphine Pesticides: Herbal ingredients,
Toxic metals (as contaminant) Lead, cadmium, mercury, arsenic particularly those grown as cultivated
Pesticides (as contaminant) DDT, chlorinated hydrocarbons, organophosphates, crops, may be contaminated by DDT or
carbamates, polychlorinated biphenyls other chlorinated hydrocarbons (Aldrin,
Chlordane, Endrin, Benzene hexachloride,
species in unlicensed herbal medicines has (seventeen cases with twelve fatalities) and Heptachlor, etc.), organophosphates
resulted in cases of nephrotoxicity and Japan (ten cases of renal failure). Recently, (Malathion, Parathion, Demeton,
carcinogenicity in Europe, China, Japan the FDA has reported two cases of serious Ethion, etc.), carbamates (Zineb, Ziram,
and USA. Concerns were first raised about renal disease due to Aristolochia being Thiram etc.) or polychlorinated biphenyls
the effects of products containing substituted for Clematis species in a (2, 4-D, 2, 4, 5-T, etc.). Limit tests are
aristolochic acids in Belgium where since dietary supplement. necessary for acceptable levels of pesticide
1993 over 100 cases of irreversible contamination of herbal ingredients34.
nephropathy have been reported in young Microbial contamination: Aerobic
women attending a slimming clinic. The bacteria and fungi are normally present Fumigants: Ethylene oxide, methyl
nephrotoxicity was traced to the in plant material and their number may bromide and phosphine have been used
inadvertent use of the toxic Aristolochia increase due to faulty growth, harvesting, to control pests, which contaminate
fangchi Wu ex Chow & Hwang root storage or processing. Herbal ingredients, herbal ingredients. The use of ethylene
in the formulations as a substitute for particularly those with high starch content, oxide as a fumigant with herbal drugs is
Stephania tetrandra Moore. Other may be prone to increased microbial no longer permitted in Europe due to
cases have been reported in China growth. It is not uncommon for herbal concerns about carcinogenic residues.
Vol 8(1) January-February 2009 61

8. General Article
Toxic metals: Lead, cadmium, mercury, uterine contractions. Herbs that contain potential drug-herb interactions and
thallium and arsenic have been shown to irritant volatile oils include ground ivy, possible side effects37-39.
be contaminants of some herbal juniper, parsley, pennyroyal, sage, pansy
ingredients. Limit tests for such toxic and yarrow. Some of these oils contain Conclusion
metals may be needed for certain herbal the terpenoid constituent, thujone, which With the global increase in the
ingredients. is known to be abortifacient. Pennyroyal use of traditional/complementary and
oil also contains the hepatotoxic terpenoidalternative medicines in many parts of
Other contaminants: Tests to limit other constituent, pulegone. A case of liver world, policy-makers, health professionals
contaminants such as endotoxins, failure in a woman who ingested and the public are wrestling with questions
mycotoxins and radionuclides may need pennyroyal oil as an abortifacient has beenabout the safety, quality, availability,
to be considered to ensure suitable quality documented. A stimulant or spasmolytic preservation and further development of
for medicinal purposes34. action on uterine muscle has been this type of healthcare. Although herbs
documented for some herbal ingredients have promising potential and are being
5. Specific patient groups including Blue cohosh, Jamaica increasingly used, many of them are
motherwort, Nettle and Raspberry. Some untested and their use is not monitored.
may be at risk
herbal teas contain laxative herbal As a result, knowledge of their potential
ingredients such as senna and cascara. In side-effects is limited. This makes
Pregnant/nursing mothers: Few
general stimulant laxative preparations areidentification of the safest and most
conventional medicines have been
not recommended during pregnancy and effective therapies and promotion of their
established as safe to take during
the use of unstandardized laxative rational use even more difficult. If
pregnancy and it is generally recognized
preparations is particularly unsuitable35, 36.
phytotheraphy is to be promoted as a
that no medicine should be taken unless
the benefit to the mother outweighs any source of healthcare, efforts must be made
Pediatric use: Herbal remedies should to promote its rational use, and
possible risk to the foetus. This rule should
be used with caution in children and identification of the safest and most
also be applied to herbal medicinal
medical advice should be sought if in effective therapies will be crucial.
products. However, herbal products are
doubt. Chamomile is a popular remedy
often promoted to the public as being
used to treat teething pains in babies. References
natural and completely safe alternatives
However, Chamomile is known to contain 1. De Smet PAGM, The role of plant derived drugs
to conventional medicines35. Many herbs
allergenic sesquiterpene lactones and and herbal medicines in healthcare, Drugs,
should not be used during pregnancy, or 1997, 54, 801-840.
should therefore be used with caution. The
when nursing. These include Aloe,
administration of herbal teas to children
Angelica, Anise, Arnica, Ashwagandha, 2. Blumenthal M, Harvard study estimates
needs to be considered carefully and consumers spend $5.1 billion on herbal
Cascara, Comfrey, Cubeb, Ephedra,
professional advice may be needed35. products? HerbalGram, 1999, 45, 68-74.
Feverfew, Gymnema, Juniper, Lemongrass,
Licorice, Lobelia, Myrrh, Parsley,
Elderly: A recent review has considered 3. Blumenthal M, Herb industry sees mergers,
Rhodiola, Sarsaparilla, Senna and Uva acquisitions, and entry by pharmaceutical
the evidence available on the use of a
Ursi36. giants in 1998, HerbalGram, 1999, 45,
number of herbal medicinal products by 67-68.
Many herbs are traditionally
the elderly people. Whilst the treatments
reputed to be abortifacient and for some
like St. John’s Wort, Valerian, Ginkgo may 4. MCA Press Releases: Concern over Quality and
this reputation can be attributed to their Safety Standards of Traditional Chinese
offer considerable benefits for a range of
volatile oil component. A number of Medicines, September 2001.
conditions, there is need for caution when
volatile oils are irritant to the genito-
herbal medicinal products are used by the 5. MCA Notifications on Safety of Kava-kava
urinary tract if ingested and may induce
elderly particularly with regard to products, December 2001-July 2002.
62 Natural Product Radiance

9. General Article
6. Grünwald J, The European phytomedicines 17. De Smet PAGM, Aristolochia species in interactions, Arch Inter Med, 1998, 158,
market: figures, trends, analysis, Adverse effects of herbal drugs, Vol.1, Berlin: 2200-2211.
HerbalGram, 1995, 34, 60-65. Springer Verlag, 1992.
30. Brown R, Potential interactrions of herbal
7. Roberts JE and Tyler VE, Tyler’s Herbs of 18. D’Arcy PF, Adverse reactions and interactions medicines with antipsychotics, antidepressants
Choice, The Therapeutic Use of with herbal medicines, Part 1, Adverse Drug and hypnotics, Eur J Herb Med, 1997,
Phytomedicinals, The Haworth Press,Inc., React Toxicol Rev, 1991, 10, 189-208. 3(2), 25-28.
New York, 1998.
19. Mattocks AR, Chemistry and toxicology of 31. Boyle F, Herbal medicines can interfere with
8. Blumenthal M, Brusse WR, Goldberg A, pyrrolizidine alkaloids, New York: Academic breast cancer treatment, Med J Australia,
Gruenwald J, Hall T, Riggins CW and Rister Press, 1986. 1999, September 1st, 286.
RS, The Complete German Commission E
Monographs, Therapeutic Guide to Herbal 20. Anderson LA, Phillipson JD, Mistletoe –The 32. European Pharmacopoeia, 4th edition, 2002,
Medicines, The American Botanical Council, magic herb, Pharm J, 1982, 229, 437-439. Strasbourg: Council of Europe, 2002.
Austin, TX, USA, 1998.
21. Tyler VE, The Honest Herbal, 3rd Edn. New 33. Cuzzolin L et al, Safety implications regarding
9. De Smet PAGM, Health Risks of Herbal York: Howarth Press, 1993. use of phytomedicine, Eur J Clin
Remedies, Drug Safety, 1995, 13(2), 81-93. Pharmacol, 2006, 62, 37-42.
22. Chandler RF, Phillipson JD and Anderson LA,
10. Barnes J, Mills SY, Abbot NC, Willoughby M, Controversial laetrile, Pharm J, 1984, 232, 34. Roulet M, Laurini R, Rivier L and Calame A,
and Ernst E, Different standards for reporting 330-332. Hepatic veno-occlusive disease in newborn
ADRs to herbal remedies and conventional infant of a woman drinking herbal tea,
OTC medicines: face-to-face interviews with 23. Statutory Instrument (SI) 1984:87. The J Pediatr, 1988, 112, 433-436.
515 users of herbal remedies, Brit J Clinic Medicines (Cyanogenetic Substances) Order,
Pharmacol, 1998, 45, 496-500. 1984. 35. Allen JR et al, Are herbal teas safe for infants
and children, Austr Fam Physic, 1989,
11. De Smet PAGM, Adverse Effects of Herbal 24. Ljunggren B, Severe phototoxic burn following 18(8), 1017-19.
Remedies, Adv Drug React Bull, 1997, celery ingestion, Arch Dermatol, 1990,
183, 695-698. 126, 1334-1336. 36. Ernst E, Herbal Medications for common
ailments in the elderly, Drugs and Ageing
12. Shaw D et al, Traditional remedies and food 25. Boffa M J, Gilmour E and Ead R D, Celery 1999, 15(6), 423-28.
supplements, A 5-year toxicological study soup causing severe phototoxicity during PUVA
(1991-1995), Drug Safety, 1997, 17, therapy, Brit J Dermatol, 1996, 135, 37. Mashour NH, Herbal medicine for the
342-56. 330-345. treatment of cardiovascular disease, Arch
Intern Med, 1998, 158, 2225-2234.
13. Baldwin CA, Anderson LA and Phillipson JD, 26. Medicines Control Agency, Psoralea
What pharmacists should know about corylifolia fruit in Traditional Chinese 38. Michael K. Ang-Lee; Jonathan Moss; Chun-Su
ginseng, Pharm J, 1986, 237, 583-586. Medicines causing severe skin reaction, Yuan, Herbal medicines and perioperative
Current Problems, Pharmacovigilance, care, J Amer Med Assoc, 2001, 286(2),
14. D’Arcy PF, Adverse reactions and interactions 2001, 27, 12. 208-216.
with herbal medicines, Part 1. Adverse
reactions, Adverse Drug React Toxicol 27. Ernst E, Possible interactions between synthetic 39. Zhou SF, Zhou ZW, Li CG, Chen X, Yu X, Xue
Rev, 1991, 10, 189-208. and herbal medicinal products, Perfusion, CC and Herington A, Identification of drugs
2000, 13, 4-15. that interact with herbs in drug development,
15. Baldwin CA, Anderson LA and Phillipson JD, Drug Disc Today, 2007, 12, 664-673.
What pharmacists should know about 28. Fugh-Berman A, Herb-drug interactions, The
feverfew, Pharm J, 1987, 239, 237-238. Lancet, 2000, 355, 134-38.
16. Tisserand R and Balacs T, Essential oil safety, 29. Miller L, Selected clinical considerations
Edinburgh: Churchill Livingstone, 1995. focusing on known and potential drug-herb
Vol 8(1) January-February 2009 63