This file contains information about herbal toxicity and different regulatory guidelines from different countries for its regulation and control

1. HERBAL REMEDIES TOXICITY &
REGULATION
SUBMITTED BY- SK AZIZUDDIN
SUBMITTED TO- DR.OZAIR ALAM
COURSE- M.PHARM
DEPARTMENT- PHARMACEUTICAL ANALYSIS
YEAR- 2020-2022
COLLEGE NAME- JAMIA HAMDARD
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2. CONTENTS
 Introduction
 Herbal medicine(Definition)
 Toxicity of Herbal drugs
 Toxic ingredients
 Regulation of herbal drugs
 Regulation of herbal drugs in India
 New Regulatory Guidelines of Ayush
 Problems to Remote in Regulation of Herbal Drugs
 Conclusion
 References 2

3. INTRODUCTION
 Plants have been used since time immemorial for diverse purposes in the life of mankind particularly as
food, and medicines for nutrition and the treatment of diseases, respectively, in both humans and
animals. They are used in all cultures of the world and have been relied upon for several millennia to
support, promote and restore human health. They form a vital component of traditional medicine (TM)
and their use for the maintenance of health and wellbeing is a common practice in all African societies.
They are used as remedies for the prevention and treatment or management of a plethora of disease
conditions including relatively new ones such as HIV/AIDS.
 Traditional medicine used to be the only health-care system available to the whole of the African
population prior to the introduction of allopathic or conventional medicine . The practice received
international recognition after the 1978 Alma Ata Conference Declaration, which aimed to achieve
primary health care for all by the year 2000 through the use of traditional medicine . TM, especially herbal
medicine, still forms the backbone of rural health care in Africa, supporting an estimated 80–90% of the
population. Not only in Africa but also in the whole world.
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4. HERBAL MEDICINE
 Herbal medicine is also known as phytochemicals or botanical medicine. According to World Health
Organization (WHO), herbal medicine includes ‘herbs, herbal materials, herbal preparations and finished
herbal products, that contain active ingredient parts of plants or other plant materials or combinations
thereof’ .
 Herbal medicine is generally considered as an integral part of dietary supplement. There is a growing
interest in herbal medicine due to its long history of application and general belief that herbs are natural
and intrinsically safe. According to WHO, approximately 4 billion of people, 80% of the world population,
rely on traditional herbal medicine for their primary health care
 In recent years, utilisation of herbal remedies as a dietary supplement for disease prevention or as
alternative/complementary medicine (CAM) for disease treatment has become increasingly popular. A
wide variety of herbal medicine/products are readily available in the market all over the world. It is
estimated that a significant percentage of population in developed countries such as Canada (70%),
France (49%), Australia (48%), USA (42%) and Belgium (31%) have used CAM at least once for health care
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5. TOXICITY OF HERBAL DRUGS
 Herbal remedies are plant-based, as in fact are many orthodox drugs - some 25% of present
pharmaceutical preparations contain at least one active ingredient extracted from plant sources
(Farnsworth, 1981). Moreover, thousands of our present drugs were originally derived from plants,
including digitalis (foxglove), aspirin (willow and meadowsweet) and paclitaxel (Taxol).However, in the
case of orthodox drugs the active ingredient is isolated from the plant, chemically standardized, subjected
to critical clinical assessment and then often replaced with a synthetic analogue. In contrast, the herbalist
uses mixtures of diverse herbal ingredients of varying potency. Potency depends on the part of the plant
used - for example root, stem, leaves or fruits - the time of the year it is picked, and the actual species of
plant used: for example, ginseng may refer to many Panax and Eleutherococcus species.
 Because potency refers to the amount of drug required evoking a response, if the potency of the
formulation of the herbal remedy is unknown it is difficult to know what dose to prescribe to get the
desired effect without causing problems of toxicity. An example of this problem is provided by mistletoe,
the popular name for 1300 species of evergreen, including the European variety Viscum album. Mistletoe
is used as an antispasmodic, diuretic and hypotensive, and some claim it has anti-cancer properties.
Mistletoe extract contains at least three types of potentially toxic compounds: alkaloids - some of which
may be cytotoxic - viscotoxins and lectins, which have hemagglutinin and mitogenic actions.
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6. ADVERSE REACTIONS & ALLERGIC REACTIONS
 Adverse reactions-Modern drugs generally undergo extensive formal testing for therapeutic and adverse
effects before being licensed. In this way drug regulatory bodies ensure that the risk of adverse effects is
small and within acceptable limits. No such controls exist for the majority of herbal remedies, however.
They do not come under the aegis of the regulatory bodies and are not required to undergo systematic
testing. Consequently our knowledge of their potential adverse effects and interactions is limited. In the
UK and the USA herbal remedies are considered as dietary supplements rather than as drugs.
Consequently companies selling them cannot make any claims about their therapeutic effects and they
give no advice about their adverse effects or contraindications gives examples of some known medically
serious adverse effects of herbal preparations.
 Allergic reactions- Like orthodox drugs, herbal preparations can result in hypersensitivity reactions, which
can range from dermatitis through to anaphylactic shock. For example, tea tree oil - widely used as a
topical disinfectant - or chamomile can cause allergic reactions Mutagenic reactions Anthranoid laxatives
such as aloe, cascara, rhubarb and Senna have Genotoxic potential and have been associated with
colorectal cancer in epidemiological studies in humans. Chaparral may also be mutagenic. One case has
been described where a patient developed cystic renal cell carcinoma after regularly drinking Chaparral
tea.
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7. DRUG INTERACTIONS & CONTAMINATION
 Drug interactions- Most consumers believe herbal medicines are harmless, so they have no qualms with taking
them in along with prescribed conventional medicines. In addition, many immigrants to the UK have their own
traditional medicines, which they may combine with orthodox medical care (D'Arcy, 1993). Both these practices
can lead to harmful herb-drug interactions. This problem is exacerbated because at least 30% of patients do not
tell their doctor that they are using them (Eisenberg et al, 1993; Yoon and Horne, 2001). This is either because
patients do not consider herbal remedies as 'drugs', and so when asked for a history of their medications do not
mention them, or because they are reluctant to mention them for fear of a negative response from the
practitioner. It is therefore vital that clinicians include questions about herbal remedies in their routine drug
histories, and be informed rather than judgmental about their use.
 Contamination- Herbal medicines are not required to undergo the same quality checks as conventional drugs
and so they may be contaminated or adulterated. For example, many Asian and Indian herbal remedies have
been found to contain heavy metals such as lead, arsenic and mercury. One of the worst examples of
contamination causing adverse effects occurred in the USA in 1989, where there was an outbreak of
eosinophilia-myalgia syndrome associated with the use of Tryptophan, an over-the-counter dietary supplement
used for weight loss (Anon, 1999). More than 1500 cases were reported, including 38 deaths. More than 95% of
the cases were traced to an individual Japanese supplier. Researchers found some trace-level impurities,
suggesting that a contaminated batch of L-tryptophan contributed to the outbreak.
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8. FALSE AUTHENTICATION
 False authentication can occur inadvertently or deliberately. An example of this is Ginseng preparations.
Only Asian ginseng contains the active compounds ginsenosides, but commercial preparations often do
not make this clear. More seriously, ingredients may be included which are not identified, including potent
orthodox drugs such as digitalis, steroids, active oestrogens, phenacetin and glibenclamide. Finally, one
ingredient can be replaced with another. This led to an outbreak of fibrosing interstitial nephritis in
Germany and France when 'Guang fangi‘ containing nephrotoxic aristolochic acids was substituted for the
Chinese drug 'Fangji. The use of herbal medications in the United States over the past decade has
increased dramatically and there are over 29,000 products on the market. In the United States, as many as
65 percent of the population report the use of complementary and alternative medical (CAM) therapies.
 Women are more likely to use complementary medicine, and non-Hispanic whites are more likely than
other racial groups. Use is highest in persons between the ages of 35 and 55 years. In 1997, the out-of-
pocket cost for all complementary and alternative therapies was estimated to be $27 billion while $19
billion was spent for dietary supplements .Use of herbal medications can be traced back as far as ancient
China, India, and Sumeria, and formulations have been expanded upon over the centuries .Many patients
consider "natural" herbal remedies to be completely free of unwanted side effects. This is concerning
since many herbal products have biological activity that can lead to severe toxicity. Fewer than 40 percent
of patients disclose to their physician that they are using these products.
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9. TOXIC INGREDIENTS
 Botanical supplements containing toxic constituents, such as liver toxins or carcinogens (chemicals with
potential to cause cancer), do occasionally cause adverse reactions, but as a rule, these supplements are
quickly withdrawn from the market once a potential problem has been identified. Some may still be sold
in supplements imported from Asia or Europe.
 The following is a partial list of botanicals with potentially toxic constituents: Aconite, Alfa alfa , Aloevera,
Borage, Calamus, Chaparrel ,Coltsfoot, Comfrey ,Ephedra, Germander , Ginkgo biloba, Ginseng,
Glycyrrhiza glabra (Licorice) Isapghul, Sassafras , Senna , Silybum marianum , St. John’s wort etc. A few of
the above are briefly covered below.
 Aconite- Aconite alkaloids contained in the root-stocks of plants of Aconitum family are accredited with
analgesic and anti-inflammatory effects within several systems of traditional medicine and are still widely
proposed for the treatment of rheumatism, neuralgia and cardiac complaints.
 Alfa alfa- The herb widely used in Homeopathy, is said to contain vitamins A, C, E and K as well as calcium,
potassium, phosphorus and iron. However it has been reported that the use of this herb can induce
Systemic Lupus Erythromatosus (SLE) like syndrome in individuals predisposed to this condition.
 Aloevera- Seventh most widely used herb for centuries as a treatment for minor bruises and is
increasingly being used in products for internal consumption. Long term use of aloe latex could results in
potassium deficiency so the laxatives containing anthraquinone glycosides should not be used
continuously for longer than 1-2 weeks owing to the danger of electrolyte imbalance.
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10. TOXIC INGREDIENTS(CONTINUE)
 Comferey: The herb was used by Greek Physicians in the first century as a safe drug in the form of
poultice to heal wounds and as a tea to help knit broken bones. In late 1970,s scientists discovered that it
contains pyrrolizidine alkaloids which are known to be hepatotoxic and has been associated with
obstruction of blood flow to the liver, possibly leading to hepatotoxic reactions besides being a risk for
cancer.
 Ephedra: The herb has been used in traditional Chinese medicine since antiquity for the treatment of
respiratory ailments. The drug has been advertised as a supposedly safe, natural product for weight loss,
body building and mood evaluation. Recently the drug became highly controversial due to its use in
slimming formulas and products claiming to deliver a "legal high" resulting in serious health hazards.
Ephedra has many side effects including restlessness, irritability, increased blood pressure and heart
rhythm disorders. The alkaloid ephedrine contained in ephedra herb can cause serious toxic reactions
ranging from liver damage to severe high blood pressure and heart problems.
 Ginkgo biloba: Ginkgo fruits and seeds have been used medicinally for thousands of years as a
supplement to improve mental alertness and related memory problems. Researchers have shown that the
extract is a potent inhibitor of platelet-activating factor and long term use has been associated with
increased bleeding time, spontaneous haemorrhage and sub dural haematomas (Rowin and Lewis, 1996).
 Isapghul: Isapghul which is considered to be the safest and largely used for its demulcent and laxative
properties since centuries is reported to have adverse reactions including bronchospasm, asthma and
intestinal obstruction. If swallowed dried it may cause oesophageal obstruction.
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11. TOXICITY OF HERBAL MEDICINES
 Toxicity of Chinese herbal medicines-:
 It is estimated that there are 7000 species of medicinal plants in China and, of the 150 species most
commonly used, 10 are toxic." Chan et al" report that in Hong Kong, most cases of serious poisoning by
CHMare related to the use of Caowu, the root of Aconitum kusnezoffii, and Chuanwa., the main root of
Aconitum carmichaeli. These herbs contain variable amounts of highly toxic alkaloids, including a conitine,
which activate sodium channels and cause widespread excitation of cellular membranes.
 Several herbal preparations containing aconitine alkaloids, for example, Monkshood (Aconitum spp.), are
commonly used in CHM to treat arthritic, rheumatic and musculoskeletal pain. The alkaloids have
analgesic, antipyretic and local anaesthetic properties but they are potentially toxic and there is a narrow
margin of safety between a therapeutic and toxic dose.v-" The toxic effects include severe cardiac
arrhythmias, nausea., vomiting, generalised weakness, numbness and paraesthesia. There is no antidote
for aconitine poisoning.
 A number of cases of accidental aconitine poisoning following ingestion of CHM preparations have been
reported."?" Dickens et at" report 30 accidental aconitine poisonings, in Hong Kong during the period
1989-1994. In at least 17 cases, intoxication was life threatening requiring management in an intensive
care unit, and three patients died. 18 All 17 patients developed symptoms of aconite toxicity within two
hours of herb ingestion; most developed tachyarrhythmia's. In two cases ventricular tachycardia and
fibrillation resulted in death within 12 hours of taking CHM containing aconitine.
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12. REGULATION OF HERBAL DRUGS
 Need for regulation of Herbal drugs- Most serious side effects originate from overuse or misuse of such
medicines. The likelihood of side effects increases when the production and sale of such products is
largely uncontrolled and or unregulated and the consumer is not adequately informed about their proper
uses. While in some countries herbal medicines are regulated through official controls and rigorous
manufacturing standards, this is not so everywhere. In Germany, for example, where herbal products are
sold as "phytomedicines" they are subject to the same criteria for their safety, efficacy and quality as
applicable to other drugs. Regulatory controls are therefore considered necessary to safeguard Drug
interactions with herbal drugs. So it is always wise to consult a qualified medical practitioner having
clinical herbal experience in case of any doubt about the compatibility of herb and the drugs you intend
to take (WHO Reports, 1997, 2002).
 The current emphasis is on screening the environment for man-made genotoxic and carcinogenic
compounds .They detracts from studies on the possible health hazard or beneficial effects of naturally
occurring agents to which humans are daily exposed in their day to day life . The simple phenolics, belong
to this category of compounds. They are ubiquitous among plants, used as food additives, and ingested
daily in milligram quantities. They are also known to induce double-strand DNA breaks, DNA adducts,
mutations and chromosome aberrations in a great variety of test systems. 12

13. REGULATION OF HERBAL DRUGS(CONTINUE..)
 However, both in vitro and in vivo assays have proved that they can suppress the genotoxic activity of numerous
carcinogenic compounds. Some studies on animal models revealed that, phenolics induce precancerous lesions,
papillomas and cancers, act as cocarcinogens, and exert a promoting effect in various rodent assays. At the initiation and
promotion stages induced by carcinogens and promoters of different molecular structures. phenolics have proved to be
potent inhibitors of carcinogenesis . The extent to which a health hazard or protective activity of complex dietary
mixtures is due to their phenolic content needs to be confirmed by further research. In addition, these multiple,
occasionally contradictory functions of simple phenolics make it difficult to propose their use as chemo preventive
agents (Stich 1991).
 In India, manufacture, sale, export and import of herbal medicines are regulated as per the Drugs and Cosmetics Act,
1940. Most of the traditional medicinal products are available as over the counter (OTC) drugs. Duration of a license to
sell herbal drugs by a pharmacy is five years from the issue/renewal of a license. For manufacturing a herbal drug,
application needs to submitted to the state licensing authority. On receipt of application authority will verify the
statements and will inspect manufacturing and testing establishment in accordance with the provisions of rule. If
authority is satisfied the application will be forwarded to central license approving authority and license will be issued if
requirements are meet. Employee requirements of a manufacturing unit include a graduate in pharmacy or
pharmaceutical chemistry, a graduate in science, a graduate in medicine.
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14. CURRENT REGULATORY PERSPECTIVE OF HERBAL DRUGS
 Foreign organic matter (FOM)
 The Foreign organic matter is a common contaminant in the herbal drugs. As per WHO, any matter or residue that is present
apart from labelled description of monograph can be consider as foreign organic matter.
 The FOM may also be a moulds or insects, including excreta and visible contaminant such as sand or silicaceous matter,
poisonous harmful foreign matter, chemical residues and animal matters such as insects and microbes, which can produce
toxins, are also among the potential contaminants of herbal medicines (WHO, 2004, 2003; EMEA, 2002).
 FOM should be regulated in market within limit as per WHO guidelines. Even though many death issues happening due to
foreign contaminants, there are no scientific evidences or documentation in form of literature or publications. Hence this
became difficult for the authors to represent the clinical data in this article.
 Phytochemical complexity of Phyto-pharmaceuticals
 Plant consist diversity in its phytoconstituents, it is quite difficult to have a clear total phytochemical data that is responsible
for targeted biological activity. It is mandate to know clear total phytochemical fingerprint nature of each plant. Even in 21st
century after having modern tools like chromatography and spectroscopy, the modern sciences failed to document total
phytochemical finger print and complex interactions between phytochemicals. Still the concept of multitargeting effect of
phototherapeutics is unclear (Efferth & Koch, 2011).
 Even incidents like discovery of hyperforin proved that hypericin is less potent and stable than hyperforin, till 19th to 20th
century, Science assume that hypericin is only the phytochemical marker responsible for various therapeutics and it was
changed after discovery of hyperforin (Vollmer & Rosenson, 2004). Even for the regulatory agencies it has become a big
issue to regulate and document the phytochemical complexity reactions.
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15. REGULATION OF HERBAL DRUGS IN INDIA
 In India, traditional medicines are governed by the Drugs and Cosmetics Act of 1940 and the Drugs and Cosmetics Rules
of 1945. They regulate the import, manufacture, distribution and sale of drugs and cosmetics. In 1959, the Government
of India recognized the traditional Indian systems of medicine and amended the Drugs and Cosmetics Act to include
drugs which are derived from traditional Indian medicine. No products derived from traditional systems may be
manufactured without a licence from the State Drug Control Authorities. Patent and proprietary medicines derived from
the traditional systems must contain ingredients which are mentioned in the recognized books of the above systems, as
specified in the Drugs and Cosmetics Act. The government is advised by a special committee and an advisory board for
Ayurvedic, Siddha and Unani drugs. Pharmacopoeia committees have been constituted to prepare pharmacopoeias for
all these systems.
 In 1993, an expert committee appointed by the Indian government developed guidelines for the safety and efficacy of
herbal medicines which were intended to be incorporated into the Drugs and Cosmetics Act and rules. It was proposed
that no new herbal medicines other than those authorized by the licensing authorities be allowed to be manufactured
or marketed, except for those mentioned in and manufactured in compliance with the formulae given in the
"authoritative" books for Ayurveda, Siddha and Unani herbal medicines. A manufacturer of a new herbal medicine must
include safety data and appropriate efficacy data in the marketing authorization application. Herbal preparations are
defined as natural products in which the predominant active constituents are of plant origin. A classification for herbal
medicines was proposed depending on their market availability, and the nature of the herbs:
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16. Category 1: already in use for more than 5 years
Category 2: in use for less than 5 years
Category 3: new medicines.
The classification of herbal medicines depends on whether they contain processed or unprocessed parts of plants
and whether they contain potentially poisonous plants. Requirements for safety and efficacy vary
according to the classification and market availability of the product. Depending on the nature of herbs and market
availability, different requirements exist for submission of clinical trial data and toxicity data.
Labelling Requirements
Labelling should include name of the drug, content, the name, address of the manufacturer, manufacturing licence number,
batch or lot number, and date of expiry, if any. If any preparation contains not less than 3 per cent by volume of alcohol the
quantity, of alcohol shall be stated in terms of the average percentage by volume of absolute alcohol in the finished products.
Misbranded drugs
ASU drugs are deemed to be misbranded: If coloured or coated to conceal the damage or made appear better than
therapeutic value; If it is not labelled in prescribed manner; If label or container accompanying drug bears any false claim or
misleading
(Mukherjee et al., 2007).
Adulterated drugs
ASU drugs are deemed to be adulterated if it consists of filthy, or decomposed material, if prepared, packed or stored under
insanitary conditions; if its container contains any poisonous or deleterious substance; color other than one which is
prescribed; harmful or toxic substance; if any substance mixed to reduce its
quality or strength (Mukherjee et al., 2007).
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17. Spurious drugs
ASU drugs are deemed to be spurious if it is sold or offered under another name, if it is an imitation or
substitute for another drug, if the label or container bears the name of an individual or company which is
fictious, if it has been substituted by other drug. Central government. can prohibit manufacture of ASU if
drug involves any risk to human beings or animals, drug does not have the therapeutic value claimed.
Standards are to be complied with in manufacture for sale or for distribution of Ayurvedic, Siddha and
Unani Drugs (Mukherjee et al., 2007).
Import of Manufacture of New Drug for Clinical Trials or Marketing
A drug, as defined in the Act including bulk drug substance which has not been used in the country to any
significant extent under the conditions prescribed, recommended or suggested in the labelling thereof and has
not been recognized as effective and safe by the licensing authority mentioned under Rule 21 for the proposed
claims. Going by statutory provisions, there exist two types of Ayurvedic medicines- one being the classical
medicine as mentioned in the authoritative books of Ayurveda and proprietary medicines. The former group of
medicine is manufactured and named in accordance with the formulations described in the authoritative texts,
whereas second group of medicine makes use of ingredients referred in the formulations of authoritative texts
but with intellectual intervention, innovation or invention to manufacture products different from the classical
medicine (Anonymous, 2013b).
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18. Drugs and Cosmetics 4th Amendment Rule 2008 (Rule 170) classifies traditional medicines into four
categories to which clinical study requirement is prescribed: ASU drugs manufactured in accordance with
formula as per the definition given in Section 3(a) of DCA, medicines based on aqueous extracts of
medicinal plants for indications as per approved text, Indian ethno-medicine– based drugs, and hydro
alcoholic extract–based drug, whereas medicines under category III and IV need to conduct clinical trials
for licensing. Although Ayurvedic medicines are known for their long history of safe and effective use,
validation of safety and efficacy using scientific and evidence-based methodologies is needed for the
purpose of universal acceptability, for gaining confidence of practitioners and to offer satisfaction to end
users of the products. In this perspective, clinical trials on Ayurvedic medicines need to be guided
according to the principle of Good Clinical Practice. (Anonymous, 2013b).
Non-clinical studies need to be conducted. Information provided should include data relating to non
clinical pharmacology and toxicology. The relevant results should be provided in summary form, stating
the methodology used, the results, and a discussion of the relevance of the findings to the investigated
therapeutic effects besides the possible unfavourable effects in humans.
• The information provided may include the following, as appropriate:
• Species used
• Number and sex of animals in each group
• Unit dose (mg/kg)
• Dose interval
• Route of administration
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19. REGULATION OF HERBAL DRUGS IN INDIA(CONTINUE…)
 As per the rule no new drug shall be imported/manufactured, except under, and in accordance with, the
permission granted by the licensing authority. An application for the grant of permission to import a new drug
shall be made in to the licensing authority. The importer of a new drug when applying for permission, shall
submit data as given in Appendix I to Schedule Y including the results of local clinical trials carried out in
accordance with the guidelines specified in that schedule and submit the report of such clinical trials in the
format given in appendix II to the said schedule. Provided further that the submission of requirements relating
to toxicology, reproduction studies, teratogenic studies, perinatal studies, mutagenicity and carcinogenicity
may be modified or relaxed in case of new drugs approved and marketed for several years in other countries
if it is satisfied that there is adequate published evidence regarding the safety of the drug, subject to the other
provisions of these rules. As per the rule no clinical trial for a new drug, whether for clinical investigation or
any clinical experiment by any institution, shall be conducted except under, and in accordance with, the
permission, in writing, of the licensing authority. An application for grant of permission to conduct.(a) human
clinical trials (Phase-I) on a new drug shall be made to the licensing authority in Form 44 accompanied by a
fee of fifty thousand rupees and such information and data as required under Schedule Y. (b) exploratory
clinical trials (Phase-II) on a new drug shall be made on the basis of data emerging from Phase I trial; (c)
confirmatory clinical trials (Phase-III) on a new drug shall be made on the basis of the data emerging from
Phase-II and where necessary, data emerging from Phase-I. The licensing authority after being satisfied with
the clinical trials, shall grant permission
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24. CONCLUSION
 As globally, there is a high demand and trust towards herbal therapies and it is must to have regulatory policies in
order to meet the challenges like content uniformity, stability, bio similarity, clinical toxicity issues. Hence this
review is explaining the need on the modern perspectives in regulating quality, safety and efficacy of herbal
medicine.
 The traditional medical systems are part of a time-tested culture and honoured by people still today. For more
than 3,000 years, these traditions have successfully set an example of natural resource use in curing many
complex diseases. Many advantages of such eco-friendly traditions exist. The plants used for various therapies
are readily available, easy to transport, and have a relatively long shelf life. The most important advantage of
herbal medicine is the minimal side effects, and relatively low cost compared to the synthetic medicines. The
success of medicinal plants sector mainly depends on the awareness and interest of the farmers as well as its
other stakeholders, supportive government policies, availability of assured markets, profitable price levels, and
assess to simple and appropriate agro-techniques.
 To conclude, not all botanical/pharmaceutical interactions are harmful. For example, in some cases, botanicals
can enhance the effect of a pharmaceuticals, thus allowing individuals to reduce their dosage Even a potent
poison becomes the best drug on proper dosage administration. 24

25. REFERENCES
 Article followed
 Herbal Medicine: Toxicity and Recent Trends in Assessing Their Potential Toxic Effects.
 POSSIBLE TOXICITY OF HERBAL REMEDIES
 Herbal drug toxicity and safety evaluation of traditional medicines
 Toxicity and Safety Implications of Herbal Medicines Used in Africa
 Concerns regarding the safety and toxicity of medicinal plants - An overview
 CURRENT REGULATORY PERSPECTIVE OF HERBAL DRUGS
 Regulatory Situation of Herbal Medicines A worldwide Review
 Regulations for Herbal Medicine-Worldwide
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