1

CHAPTER ONE

INTRODUCTION

For centuries the therapeutic properties of various medicinal plants have been used

to treat human diseases. About 60- 90% of populations living in developing

countries follow traditional and herbal medicine almost exclusively and apply them

as a normal part of primary health care. To the traditional medicines aromatic

plants are mostly used as antimicrobial agents and their oils have been known since

ancient times to possess antibacterial and antioxidant activities (Penesyan, Gillings

and Paulsen, 2015).

Microbial infections remain a threat to millions of lives of those individuals and

currently there is an increased problem of antibiotic resistance due to microbial

persistence (Ajayi, 2018).

The dramatic increase of bacteria resistance to the common antibiotics in use

increases the demand to search for the new, potential and alternative active

compound in plants to treat the bacterial infection that cause by those antibiotic

resistance bacteria. In addition, source of medicinal plant are more accessible to

human beings in the developing or under developing country compared to those of

orthodox medicines. Natural drugs that are produced from medicinal plants are

also safer to consume, less toxic and normally has lower side effect compared with
 2

conventional drugs which are manufactured by chemical compound

(Bandaranayake, 2016).

Medicinal plant materials normally carry a large number of microbes originating

from the soil. Microorganisms of various kinds are normally adhered to leaves,

stem, flowers, seeds, and roots (Faleye, Odeyemi and Olagboye, 2015).

As the global use of herbal medicinal products continues to grow and many newer

products are introduced into the market, public health issues, and concerns

surrounding their safety are also increasingly recognized. Although some herbal

medicines have promising potential and are widely used, many of them remain

untested and their use also not monitored. This makes knowledge of their potential

adverse effects very limited and identification of the safest and most effective

therapies as well as the promotion of their rational use more difficult. It is also

common knowledge that the safety of most herbal products is further compromised

by lack of suitable quality controls, inadequate labeling, and the absence of

appropriate patient information (Faleye et al., 2011).

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CHAPTER TWO

IMPLICATION OF HERBAL DRUGS

2.1 Herbal Medicine

Traditional medicine is defined as health practices, approaches, knowledge and

beliefs incorporating plant, animal and mineral based medicines, spiritual

therapies, manual techniques and exercises, applied singularly or in combination to

treat, diagnose and prevent illnesses and maintain well-being. Herbal medicine,

also known as herbalism or botanical medicine, is a medical system based on the

use of plants or plant extracts that may be eaten or applied to the skin. Since

ancient times, herbal medicine has been used by many different cultures

throughout the world to treat illness and to assist bodily functions. While herbal

medicine is not a licensed profession in the United States, herbal remedies in the

form of extracts, tinctures, capsules and tablets as well as teas may be

recommended by healthcare practitioners of many different disciplines as a

practical way to address a wide variety of medical conditions (Atanasov,

Waltenberger, Pferschy-Wenzig, Linder, Wawrosch, Uhrin and Temml, 2015).

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2.2 Good Effect of Herbal Drugs

2.2.1 Efficacy of herbal drugs

During recent decades, different plant, derived extracts and phytochemicals have

been ascribed a variety of potentially health-promoting biological activities. Plants

such as Hyptis suaveolens have oil which is strongly aromatic and has been

reported to be potent for reducing bacterial and fungal growth. The juice squeezed

from the leaves, when mixed with lime juice, is drunk to cure colic, gastrointestinal

disorder and when applied to forehead, alleviate headache ( Bamidele, Ogundipe and

Shogeyinbo, 2014).

Mangifera indica (Mango) bark and leaves have astringent properties such that a

lotion and mouth-wash relieves toothache, sore gums and sore throat. An infusion

of root bark is given for diarrhea and dysentery. Vitex doniana (Hausa: ɗinya) is

being used by traditional medicine practitioners in the treatment of dysentery and

gastroenteritis (Tor-Anyiin and Anyam, 2013).

The stem bark and leaves of Garcinia kola can be used for the treatment of

diseases caused by Staphylococcus aureus (Akande and Ajao, 2014). Many other

plants are said to be of medical importance in treatment of conditions ranging from

fever, throat, intestinal, urethral, skin and venereal diseases. It is estimated that

almost 75% of the useful bioactive plants-derived pharmaceuticals used worldwide

 5

were discovered by systematic investigation of leads from traditional medicine

practitioners (Akande and Ajao, 2014).

Herbalists believe that the use of tinctures and herbal tonic can help the body to

heal itself by restoring harmony and balance and activating the body’s life force.

Their remedies are extracted from leaves, petals and roots, barks and plants possess

a complex mixture of different compounds, a principle referred to as “herbal

synergy”. While a conventional pharmaceutical will usually be a single active

ingredient, the idea of herbal synergy explains that the hundreds if not thousands of

constituents of a plant extract all work together to treat an illness. For example,

ephedrine, an early anti-asthma drug was first isolated from the herb Ephedra

traditionally used to treat chest complaints. One of the side effects of ephedrine is

that it raises the blood pressure. Herbalist point out that among many compounds

found in the plant itself is one that lowers blood pressure so, the herbal remedy

contains a compound to treat the chest, but also to counteract the side effects of the

compound (Ojo, Anibijuwon and Ojo, 2010). In fact, numerous researches in vitro

and in vivo have indicated the efficacy and effectiveness of herbs in treating one

disease or the other. Plant materials are used not only in medication but also in the

control of pest and other parasites, such as mosquitoes. A compound from

Azadirachta indica (Azadirachtin) has adverse effect on endocrine system of beans

beetle Epilachna variveatis and cause sterility in the female insect and also
 6

demonstrates potency in the control of the insect in question by causing

degradation in larval epidemics preventing the larvae from molting (Ojo et al.,

2010).

2.2.2 Low cost of herbal drugs

Many people use herbal drugs because of its low cost. Herbal medicines can be

grown from seed or gathered from nature for little or no cost. Many of the

pharmaceuticals currently available to physicians have a long history of use as

herbal remedies, including opium, aspirin, digitalis, and quinine. According to the

World Health Organization, approximately 25% of modern drugs are derived from

plants because of its low cost and effectiveness (Atanasov et al., 2015).

The use of herbal remedies is more prevalent in patients with chronic diseases such

as cancer, diabetes, asthma and end-stage renal disease. Multiple factors such as

gender, age, ethnicity, education and social class are also shown to have

association with prevalence of herbal remedies use (Bishop and Lewith, 2010).

Through its use of natural products, traditional medicines offer merits over other

forms of medicine in such areas as the following: discovery of lead compounds and

drug candidates; examining drug-like activity; and exploring physicochemical,

biochemical, pharmacokinetic, and toxicological characteristics. If any form of

traditional medicines is applied successfully, it may surprisingly assist in the

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development of new drugs, thereby resulting in many benefits, such as significant

cost reductions (Abdullahi, 2011).

2.2.3 Accessibility of herbal drug

Herbal drugs have increasingly been used worldwide during the last few decades

as evidenced by rapidly growing global and national markets of herbal drugs. Now

people rely more on herbal drugs because of high price and harmful side effects of

synthetic drugs and this trend is growing not only in developing countries but in

developed countries too. A number of plants have been indicated to possess

antimicrobial properties from traditional uses (Ajayi, 2018).

The use of medicinal plants as a fundamental component of the African traditional

healthcare system is perhaps the oldest and the most assorted of all therapeutic

systems. In many parts of rural Africa, traditional healers prescribing medicinal

plants are the most easily accessible and affordable health resource available to the

local community and at times the only therapy that subsists (Fawzi, 2013). African

herbal medicine is “holistic” in the sense that it addresses issues of the soul, spirit,

and body. It is cheap and easily accessible to most people, especially the rural

population. It is also considered to be a lot safer than orthodox medicine, being

natural in origin (Ezekwesili-Ofili and Okaka, 2018).

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2.3 Bad Effect of Herbal Drug

An adverse drug reaction is defined as “a harmful or troublesome reaction, due to

intervention related to the use of a healing substance, which envisages risk from

future administration and requires prevention or explicit treatment, or alteration of

dose and method of administration, or withdrawal of the medical substance.” Any

substance with a healing effect can generate unwanted or adverse side reactions.

As with synthetic drugs, the quality, efficacy, and safety of medicinal plants must

also be assured. Despite the widespread use of herbal medicines globally and their

reported benefits, they are not completely harmless. In as much as medicinal herbs

have established therapeutic effects, they may also have the potential to induce

adverse effects if used incorrectly or in overdose. The likelihood of adverse effects

becomes more apparent due to indiscriminate, irresponsible, or nonregulated use

and lack of proper standardization. These concerns have been the focus of many

international forums on medicinal plants research and publications [53]. The rich

flora of Africa contains numerous toxic plants, though with interesting medicinal

uses. The toxic constituents (e.g., neurotoxins, cytotoxins, and metabolic toxins)

from these plants can harm the major systems of the human body (cardiovascular

system, digestive system, endocrine system, urinary system, immune system,

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muscular system, nervous system, reproductive system, respiratory system, etc.)

(Daniels and Olu, 2014).

In a survey in Lagos metropolis, Nigeria, among herbal medicine users, it was

found that herbal medicine was popular among the respondents but they appeared

to be ignorant of its potential toxicities (Bamidele et al., 2014). Several herbal

medicines have been reported to have toxic effects. Current mechanisms to track

adverse effects of herbal medicines are inadequate (Parle and Bansal, 2016).

Consumers generally consider herbal medicines as being natural and therefore safe

and view them as alternatives to conventional medications. Only very few people

who use herbal medicines informed their primary care physicians. It is therefore

likely that many adverse drugs reactions go unrecorded with either patients failing

to divulge information to health services, and no pharmacovigilance analyses are

being carried out, or the observations are not being reported to appropriate quarters

such as health regulatory bodies. Establishing a diagnosis of herbal toxicity can be

difficult. Even when herbal-related toxicity is suspected, a definitive diagnosis is

difficult to establish without proper analysis of the product or plant material. Very

few adverse reactions have been reported for herbal medicines, especially when

used concurrently with conventional or orthodox medicines (Hussin, 2011). The

results of many literature reviews suggest that the reported adverse drug reactions
 10

of herbal remedies are often due to a lack of understanding of their preparation and

appropriate use (Hussin, 2011).

In a research of liver and kidney functions in medicinal plant users in South-East

Nigeria, it was found that liver problems were the most prominent indices of

toxicity as a result of chronic use (Spigelblatt, Laine-Ammara, Pless and Guyver,

2014). Toxic components in these herbs such as alkaloids, tannins, oxalates, etc.,

may likely be responsible for such observed toxicities. Another important source of

toxicity of herbal medicines worth mentioning is microbial contamination due to

poor sanitary conditions during preparation (Ojo et al., 2010). Toxicity may also

arise as a result of herb-drug interaction in situations where there is co-

administration of herbal medicines with some conventional drugs or supplements.

Incorrect identification and misuse of plants may also lead to toxicity (Hussin,

2011).

2.3.1 Toxicity of Herbal Drug

Patients consuming herbal preparations should be aware that herbs could cause a

variety of toxic reactions. Certain groups of the population should be extra cautious

as they are more susceptible to herbal adverse reactions or toxicities. They include

pregnant and nursing women; some compounds in herbs can cross the placenta and

are clearly linked to birth defects or other problems in newborns. Children and

infants are much more sensitive than adults to the effects of all medicines including
 11

herbs. The elderly with cardiovascular problems, diabetes and other chronic

diseases may show exaggerated toxic/adverse reactions to herbs. Herbs can be

hazardous in many ways (Hussin, 2011).

The ways in which herbal products produce toxicity can be classified as follows:

1. Some herbals may contain toxic ingredients Some herbs are found to contain

toxic constituents with various potential adverse effects.

2. Unintentional substitution of the herb with a toxic species.

3. Intentional addition of drugs. The intentional addition of drugs is done to

produce the therapeutic effects or potentiate the effects of the herbals.

4. Environmental contamination of the herbs. Because herbal preparations are

usually not evaluated for purity and consistency of active components, they often

contain unintentional contaminants.

2.3.2 Toxic when taken in combination with modern medicines

When herbs with some potential for toxicity are mixed with modern medicines,

there may be potentiation of the toxicity of the herb by the metabolic and

physiological effects of the drug. In some cases, herbal use may be contraindicated

with certain disease states. Interaction of herbals with drugs may also bring about

changes in the pharmacokinetic and pharmacodynamics properties of the latter. For

example, herbal-drug interaction may cause decrease or increase in the absorption,

distribution, metabolism and excretion of the drug. The interaction may also
 12

increase or decrease the desired pharmacological effects of the drug (Spigelblatt et

al., 2014).

2.3.3 Wrong Perception about Healing Efficiency of Herbal Drug

The general perception that herbal remedies or drugs are very safe and devoid of

adverse effects is not only untrue, but also misleading. Herbs have been shown to

be capable of producing a wide range of undesirable or adverse reactions some of

which are capable of causing serious injuries, life-threatening conditions, and even

death. Numerous and irrefutable cases of poisoning have been reported in the

literature (Ernst, 2012).

An association between traditional herbal medicine use and the development of

liver fibrosis among study participants in Uganda. A number of Chinese herbal

medicines and other herbal medicines from different parts of the world have also

been implicated in cases of poisoning. Many of them have been shown to contain

toxic compounds which are capable of reacting with cellular macromolecules

including DNA, causing cellular toxicity and genotoxicity (Spigelblatt et al.,

2014).

2.3.4 Misuse and Over-use of Herbal Drugs

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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 (Tor-Anyiin and Anyam, 2013). 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 the use and

administration of 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 (Smet, 2017).

The current emphasis is on screening the environment for man-made genotoxic and

carcinogenic compounds. 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

(Smet, 2017). However, both in vitro and in vivo assays have proved that they can
 14

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 (Smet, 2017). 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 chemopreventive

agents (Stich, 2011).

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CHAPTER THREE

COMPLICATION OF HERBAL DRUGS

3.1 Nephrotoxicity of Herbal Drug

Nephrotoxicity is toxicity in the kidneys. It is a poisonous effect of some

substances, both toxic chemicals and medications, on renal function. There are

various forms, and some drugs may affect renal function in more than one way.

Nephrotoxins are substances displaying nephrotoxicity (Naesens et al., 2009).

Herbal medicine involves the use of natural compounds, which have relatively

complex active ingredients with varying degrees of side effects. Some of these

herbal medicines are known to cause nephrotoxicity, which can be overlooked by

physicians and patients due to the belief that herbal medications are innocuous.

Some of the nephrotoxic components from herbs are aristolochic acids and other

plant alkaloids (Yang et al., 2018). In addition, anthraquinones, flavonoids, and

 16

glycosides from herbs also are known to cause kidney toxicity. The kidney

manifestations of nephrotoxicity associated with herbal medicine include acute

kidney injury, CKD, nephrolithiasis, rhabdomyolysis, Fanconi syndrome, and

urothelial carcinoma. Several factors contribute to the nephrotoxicity of herbal

medicines, including the intrinsic toxicity of herbs, incorrect processing or storage,

adulteration, contamination by heavy metals, incorrect dosing, and interactions

between herbal medicines and medications (Yang et al., 2018).

3.2 Gastrointestinal Bleeding

Gastrointestinal bleeding is when bleeding occurs in any part of the gastrointestinal

tract. The gastrointestinal tract includes your esophagus, stomach, small intestine,

large intestine (colon), rectum, and anus. Gastrointestinal bleeding itself is not a

disease, but a symptom of any number of conditions. The causes and risk factors

for gastrointestinal bleeding are classified into upper or lower, depending on their

location in the gastrointestinal tract (Cochran et al., 2011).

Gastrointestinal bleeding is a life-threatening complication of gastrointestinal

diseases. There is a large variety of uncommon reasons which contribute to UGB

and might become reasons for misdiagnosis and sometimes lead to fatal

consequences (Zhang et al., 2012).

Drug-induced bleeding is commonly thought of as gastrointestinal bleeding

resulting from the use of nonsteroidal anti-inflammatory drugs (NSAIDs).

 17

Nosebleeds and abnormal bruising, in addition to gastrointestinal bleeding, may be

linked to the use of herbal drugs (Anglin et al., 2014). Hemorrhoidal bleeding may

be associated with drugs that cause constipation. In addition, other predictors that

may contribute to or cause an increase in bleeding include advancing age, the use

of multiple drugs, drug-drug interactions, and coexisting diseases or conditions

(Cochran et al., 2011).

3.3 Hypokalemia

Frequent consumption of herbal medication has been reported to cause

hypokalemia (Satko and Burkart, 2011). Hypokalemia is a low level of potassium

(K+) in the blood serum. Mild low potassium does not typically cause symptoms.

Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low

potassium also increases the risk of an abnormal heart rhythm, which is often too

slow and can cause cardiac arrest. Causes of hypokalemia include vomiting,

diarrhea, medications like furosemide and steroids, dialysis, diabetes insipidus,

hyperaldosteronism, hypomagnesemia, and not enough intake in the diet (Soar et

al., 2010).

Over consumption of herbal drugs can lead to decrease in the amount of potassium

that occurs due to excessive uptake of potassium by metabolically active cells in a

 18

blood sample after it has been drawn. It is a laboratory artifact that may occur

when blood samples remain in warm conditions for several hours before

processing (Zieg et al., 2016).

3.4 Cardiotoxicity

Cardiotoxicity is a term used for damage to heart or altering heart functions. It is a

state in which there is alteration in electrophysiological function of heart or cardiac

muscle damage, which weakens the heart causing inefficient pumping and

circulation of blood. This can be detected by symptoms such as dry, non-

productive cough, inflammation of ankles, hand, feet, and neck veins; irregular

heartbeat; tachycardia; cardiomegaly; weakness; vertigo, etc (Nudrat and Naira,

2016).

Herbal medicines are advertised to be free from side effects, which is a myth. A

large number of people still rely on herbal medicines, and some people take herbal

medicines along with routine allopathic medicines especially in cases of diabetes,

hypertension, thyroid disease, etc., where the patient is on long-term or lifelong

treatment (Maffe et al., 2013).

3.5 Health Impact of Herbal Drugs

There is a perception that ‘natural’ drugs are safe and have no side effects. Toxic

side effects of herbal medicines used in traditional societies have typically not been

reported, and this is often cited in favour of their safety. However, the lack of
 19

systematic observation has meant that even serious adverse reactions, such as the

kidney failure and liver damage caused by some plant species, have gone

unrecognised until recently. Unfortunately, even ‘natural’ drugs may have

significant toxicity (Smet, 2017). In fact, a good proportion of commonly used

pharmaceuticals is derived from natural substances. The safety of combining

natural remedies with conventional medical therapy has not been well studied.

Allergic reactions to chamomile tea used to treat colic have been reported. Infant

death has been reported following maternal ingestion of teas containing

pyrolizidine alkaloids found in herbs such as comfrey (Penesyan et al., 2015). The

ginseng abuse syndrome involves diarrhea, hypertension, insomnia, nervousness

and skin eruption. Ginseng can also interact with warfarin and digoxin (Raynor et

al., 2011). Alfalfa can induce or reactivate systemic lupus erythematosis. Bee

pollen has caused severe allergic reaction, including anaphylaxis. Feverfew has

caused mouth ulceration. The investigation into herbal toxicity is limited by the

following: the lack of a good animal model, a passive reporting system, analytical

methodology that is not well characterized, limited knowledge of active ingredients

and chemical interactions, limited knowledge of the mechanism of action,

variability in the preparation method, and interpatient variability (Philomena,

2011).

3.6 Safety and Standard of Traditional Medicines

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The growing popularity of herbal remedies is fueling and is to some extent fueled

by increasing scientific interest in herbal medicine (Ansari and Inamdar, 2010).

The 35,000-70,000 species of plants that are used for medicinal purposes, around

5,000 have been submitted for biomedical scrutiny (WHO, 2012). Scientific

evidence of efficacy is beginning to emerge from randomized controlled trials in

which herbs compare favourably with place (Ekeanyanwu, 2011).

Another reason for the growing popularity of herbal medicines is that many people

believe they are safer and more natural than pharmaceuticals. However, studies

have shown that not all natural products are safe, some poisons are also natural

(Ansari and Inamdar, 2010). Herbal medicine however natural can cause serious

illness from allergy to liver or kidney malfunction to cancer and even death (Ansari

and Inamdar, 2010). In terms of carcinogenicity for example, toxicological

potential of natural plant chemicals is roughly the same as that of synthetic

chemicals. Most herbal products on the market today have not been subjected to

drug approval process to demonstrate their safety and effectiveness. Some of them

contain mercury, lead, arsenic and corticoids and poisonous organic substances in

harmful amounts. Hepatic failure and even death following ingestion of herbal

medicine have been reported. A prospective study shows that 25% of the childhood

blindness in Nigeria and India were associated with the use of traditional eye

medicine (Ekeanyanwu, 2011).

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Standardization of herbal medicine that may contain hundreds of chemical

constituents with little or no evidence indicating which might be responsible for

the presumed or proven therapeutic effect is a particularly theory issue. Many users

of herbal medicines consider that they are safe for human consumption, an

assumption based in part on extensive prior field experience. If this concept ever

had validity, it is no longer correct. In Nigeria, teas and infusions of herbs are the

most popular traditional drug formulation available today. On a batch to batch

basis, there must be botanical, chemical and biological standardization of products

and collateral studies which would establish both the safety of the products and a

demonstration of its efficacy and meaningful shelf-life (Ekeanyanwu, 2011).

CHAPTER FOUR

CONCLUSION AND RECOMMENDATION

4.1 Conclusion

Herbal medicine is a component of alternative treatment methods and it includes

the use of different plants and their extracts due to their large benefits. It is one of

the most effective and safe treatment options and is even getting recognition from

practitioners of traditional medicine. The consumption of herbal medicines is

increasing steadily throughout the world as an alternative treatment for alleviating

a number of health problems including heart diseases, diabetes, high blood

pressure, and even certain types of cancer. However, unlike drugs, herbal products
 22

are not regulated for purity and potency. Herbal medicine can be beneficial to

consumers, but they also can cause serious side effects and potentially dangerous

conditions. Herbal medicines can cause kidney failure and liver damage in some

consumers because they contain toxic chemicals or heavy metals, or react

harmfully with other drugs, a study has found. The risk of a herbal remedy

producing an adverse reaction depends not only on the remedy and its dosage but

also on consumer-related parameters, such as age, genetics, concomitant diseases

and concurrent use of other drugs. Another important determinant of the toxicity of

herbal remedies is their quality.

4.2 Recommendation

Based on the finding about the health implication of consumption of herbal

medicine, it is recommended that;

1. People should minimize or if possible abstain from talking some herbal

medicine especially the commercially prepared herbal medicine that its

composition is not known and the seller claim that it cures every kinds of disease.

2. NAFDAC should strengthen their monitoring and regulation of herbal

preparation in Nigeria

3. Researchers should more on the toxicity and safety of herbal drug and create

awareness for the masses to be aware of the kind of medicine they should take
 23

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