68 3 Herbal Medicines: Prospects and Constraints

3.3
Constraints in Herbal Medicine

3.3.1
Reproducibility of Biological Activity of Herbal Extracts

One of the major constraints in using plants in pharmaceutical discovery is the

lack of reproducibility of activity for over 40% of plant extracts [46]. Reproducibility
is the major problem, as the activities detected in screens often do not repeat when
plants are re-sampled and re-extracted. This problem is largely due to differences
in the biochemical profiles of plants harvested at different times and locations, dif-
ferences in variety, and variation in the methods used for extraction and biological
activity determination. Furthermore, the activity and efficacy of plant ex-
tracts/medicines often results from additive or synergistic interaction effects of the
components. Therefore, a strategy should be used to evaluate the qualitative and
quantitative variations in the content of bioactive phytochemicals of plant material.
It is important to identify the different agroclimatic or stress locations, climate, mi-
croenvironment, physical and chemical stimuli often called elicitors, which quan-
titatively and qualitatively alter the content of bioactive secondary metabolites.
Thus, elicitation-induced reproducible increases which might be otherwise unde-
tected in screen, should significantly improve reliability and efficiency of plant ex-
tracts in drug discovery. Standardization, optimization, and full control of growing
conditions could result in the cost-effective and quality-controlled production of
many herbal medicines.

3.3.2
Toxicity and Adverse Effects

The general belief is that herbs are safer than pharmaceuticals because they are
natural. But the fact is, healing herbs are neither completely safe nor poisonous.
They are like other medicines. In low amounts they may be in effective while in the
right amounts they may prove beneficial. Their use in high quantities and over pro-
longed periods may prove to be injurious.
Toxicity in herbal medicine may be due to (1) accidents due to a mistake in bo-
tanical identification, (2) accidental ingestion of cardiotonic plants, (3) inappropri-
ate combinations, including the use of potentially toxic plants, (4) or plants that
interfere with conventional pharmacological therapy, such as plants containing
coumarinic derivatives, a high content of tyramine, estrogenic compounds, plants
causing irritation and allergic problems, plant containing photosensitive com-
pounds etc. [47–51]. Recent scientific research has demonstrated that many tradi-
tionally used herbal medicines are potentially toxic and some are even mutagenic
and carcinogenic [52–54]. The toxicity benchmarks for herbal drugs therefore de-
pend on purity, herbs containing toxic substances, bioavailability, and reported ad-
verse effects.
 3.3 Constraints in Herbal Medicine 69

3.3.3
Adulteration and Contamination

Adulteration and contamination of herbal medicines appears to be common in

countries that are lenient with regard to controls regulating their purity. Adultera-
tions in herbal medicine are particularly disconcerting because they are unpredict-
able. Often they remain undetected unless they can be linked to an outbreak or epi-
demic. An example is veno-occlusive disease due to ingestion of plants containing
pyrrolidizine alkaloids, which can be life threatening or fatal [55, 56].
In many cases contaminated or adulterated herbal medicines can cause signifi-
cant medical problems, especially in children [57, 58]. In a recent review on heavy
metal poisoning in children consuming herbal medicines, 13 reports were identi-
fied from Singapore, Hong Kong, the USA, the UK, and the UAE from 1975 to
2002.
Ayurvedic medicines are sometimes prepared using inorganic active constitu-
ents. Combined with environmental contamination this may increase the heavy
metal content above permissible limits in developed countries.
The Indian Government has initiated a major program under which the phar-
macopeial standards for the drugs used in the Ayurveda, Unani, and Siddha sys-
tems of medicine are being developed. The resultant pharmacopeia will help in
knowing more about the herbal drugs in use. Simultaneous use of more than one
herbal products or the use of herbal products in combination with pharmaceuticals
needs to be checked. There are chances of adverse interactions. Some of the con-
tradictions associated with poisonous drugs of the ISM are listed in Table 3.4.
Adulteration in Asian medicines mostly results from the misidentification of
plants. This has resulted in a number of serious events, primarily due to poisoning
with digitalis, belladonna, skullcap, etc. [8]. In 1998, the California Department of
Health reported that 32% of Asian patent medicines sold in the US contained un-
declared pharmaceuticals or heavy metals [60, 61]. The FDA and other investiga-
tors have also reported the presence of prescription drugs, including glyburide, sil-
denafil, colchicines, adrenal steroids, alprazolam, etc. in products claiming to con-
tain only natural ingredients [62].

3.3.4
Herb–Drug Interactions

Herbal medicines can act through a variety of mechanism to alter the pharmacok-
inetic profile of concomitantly administered drugs [63]. St John’s wort, for exam-
ple, induces the cytochrome P450 isozyme CYP 3A4 and intestinal P-glycopro-
teins, accelerating the metabolic degradation of many drugs including cyclosporin,
antiretroviral agents, digoxin, and warfarin [64].
Numerous examples exist of drug and herbal interactions. These effects may
potentiate or antagonize drug absorption or metabolism, the patient’s metabolism,
or cause unwanted side reactions such as hypersensitivity [65–67]. Care should be
Table 3.4 Some commonly used poisonous drugs in the Indian System of Medicine [59, 79].

Plant name Vernacular name Part used Common use Adverse effect (in large doses)

70
Aborus precatorius L. Indian liquorice Seed Diarrhea, dysentery, paralysis and Abrin causes edema and ecchymosi

3 Herbal Medicines: Prospects and Constraints

skin diseases, antiseptic, uterine inflammation antifertility activity,
stimulant and anticancerouss, antiestrogenic activity, abortifacient and
oxytocic activity
Aconitum casmanthum Aconite Rhizome Neuralgia, rheumatism, cardiac Narcotic, powerful sedative, arrhythmia
Stappex Holm tonic and nerve poisons and hypertension
Gloriosa superba L. Malanbar glory lily Root Anthelmintic, purgative, emetic, Antifertility, vomiting, purging,
antipyretic, expectorant and toxic gastrodynia and burning sensation
Croton tiglium L. Croton Seed Abdominal disorders, constipation, Depressor responses and
helminthiasis, inflammation, neuromuscular blockade
leukoderma and dropsy
Calotropis gigantea L. Gigantic swallow wort Latex and leaf Paralysis, purgative and intermittent Violent purgative and gastrointestinal
fevers irritant
Cannabis sativa L. Hemp Leaf Antidiarrhetic, intoxicating, stomachic Neurotoxic, respiratory arrest, nausea
and abdominal disorders, tremors, insomnia, sexual impotence
and gastrointestinal disturbance
Datura metel L. Thorn apple Seed and leaf Antihelminthic and anticancerous Insanity
Euphorbia neriifolia Milk hedge Latex Insecticidal and cardiovascular Emetic, irritant, apnea and pathological
changes in liver, heart and kidney
Papaver somniferum L. Poppy Exudate Diarrhoea, dysentery, sedative, Highly narcotic
narcotic and internal hemorrhages
Semecarpus anacardium Marking nut Fruit Antiseptic, cardiotoxic, anticarcinomic Abortive
liver tonic and uterine stimulants
Nerium indicum Mill Oleander Fruit and leaf Antibacterial, ophthalmic and Cardiac poison, paralysis and depress
cardiotonices respiration, gastrointestinal, neurological
and skin rashes
Strychnos nux vomica L. Snake wood Seed Appetizer, anthelmintic, purgative Paralysis
and stomachic
 3.3 Constraints in Herbal Medicine 71

taken to understand the effects of foods or herbal medicines during anticoagulant

therapy, in the treatment of diabetes, depression, pain, asthma, heart conditions,
or blood pressure disorders, and during slimming [8]. The scientific data about the
interactions of various herbal medicines with a drug and its pharmacokinetics and
bioavailability should be evaluated to assess the potential toxicity as well as the
pharmacological basis of efficacy [13].

3.3.5
Standardization

Standardization is an important step where the active constituents are known.

However, for many herbs the active constituents are not known. In such cases,
products may be standardized on the content of certain marker compounds. How-
ever herbal medicines rarely meet this standard for several reasons, including the
lack of scientific information about the acting pharmacological principles. The var-
iability in the content and concentration of constituents of plant material, together
with the range of extraction techniques and processing steps used by different
manufacturers results in marked variability in content and quality of commercial-
ly available herbal products [68]. The use of chromatographic techniques and
marker compounds to standardize herbal preparations promotes batch-to-batch
consistency but does not ensure consistent pharmacological activity or stability.
Consistency in composition and biological activity are prerequisites for the safe
and effective use of therapeutic agents. But standardization of correct dosage
forms is not always easy, especially in polyherbal preparations or single plants that
are not cultivated under controlled condition. And there is no guarantee that a
product contains the amount of the compound stated on the label [51].

3.3.6
Regulatory Challenges of Asian Herbal Medicine

Overall the incidence of serious adverse reactions is significantly lower with most
herbal medicines when compared with pharmaceutically derived drugs [8]. Howev-
er, the need still exists to more closely monitor practitioners and formulators of
any traditional medicine, including those of Indian origin, so that unethical prac-
tices are reduced.
For most herbal products, verification is difficult if not impossible after process-
ing has occurred. In traditional medicines that are prepared in Asian countries and
exported, the task of ensuring safety is even more difficult since the incorporation
of certain levels of potentially toxic herbs or heavy metals may not be considered
harmful in the country of origin [69]. Some Chinese and Indian Ayurvedic medi-
cines have been rejected by US, Canada and other countries on the grounds that
they contain high levels of potentially toxic elements, including heavy metals.
In the view of above problem, the authorized body for traditional medicine
“Ayush” has adopted strict guidelines for all herbal medicines (Unani, Ayurveda,
and Siddha) to be exported from India. Ayush has made it mandatory for all ISM