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Chapter-1 INTRODUCTION
Bhavik Ph. D Dissertation 1
1. INTRODUCTION
1.1 Herbal Medicine
Plant kingdom had played vital role in man‟s existence on this earth. Nature has
always been stands as a golden mark to amplify the outstanding phenomenon of
symbiosis. Medicinal plants existing even before human being made their appearance
on the earth.1Natural products have been derived from higher plants, microbes or
animals and those can be of either terrestrial or marine or aquatic origin.
Practically every country develops its own medical system, which includes the ancient
civilization of China, Egypt and India. Thus, the Indian Medical system Ayurveda
came into existence. The raw materials for Ayurvedic medicines were mostly
obtained from plant sources in the form of crude drugs such as dried herbal powders
or their extracts or mixture of products. Also, Siddha and Unani are traditional health
care systems have been flourishing for many centuriesin the country. Apart from these
systems there has been a rich heritage of ethanobotanical tradition of herbs by a
diversity of tribal communities in the country.
The medicinal preparations based on these raw materials were in the form of crude
drug. Many of these reputed medicinal plants came under chemical investigation
leading to the isolations of active principles with the advent of scientific methods.
There was continuous activity in this area since 1800 AD and many of the well known
medicinal plants were chemically analyzed and their active principles were
characterized. Soon after their isolation and characterization of these compounds,
either in pure state or in the form of extracts, became part of pharmacopoeias of
several countries. This is where herbal medicine and modern medicine have a
common link.2,3,4
1.1.1Herbal wealth of India
Now-a-days natural products are becoming an integral part of human health care
system, because of popular concern over toxicity and resistance of modern drugs.
India is one of 12 leading bio-diversity centers with presence of over 45,000 different
plant species, 15000-18000 flowering plants, 23,000 fungi, 16,000 lichens, 18,000
bryophytes and 13 million marine organisms. From this flora 15,000 to 20,000 have
good medicinal value. Among those only about 7,000 plants are used in Ayurveda,
600 in Siddha, 700 in Unaniand 30 in modern medicines.
Chapter-1 INTRODUCTION
Bhavik Ph. D Dissertation 2
The WHO estimated that 80% of the population of developing countries relies on
traditional medicines, mostly plant drugs, for their primary health care needs. Also,
modern Pharmacopoeias still contain at least 25% drugs derived from plants and
many others which are synthetic analogues built on prototype compounds isolated
from plants. Demand for medicinal plant is increasing in both developing and
developed countries due to increasing recognition of natural products, being non-
narcotic, having less side-effect, easily available at affordable prices and sometime
the only source of health care available to the poor. Medicinal plant sector has
traditionally occupied an important position in the socio-cultural, spiritual and
medicinal arena of rural and tribal lives of India.5
Demand for medicinal plant is increasing in both developing and developed countries,
and the bulk of the material trade is still from wild harvested sources on forest land
and only a very small number of species are cultivated. The expanding trade in
medicinal plants has serious implications on the survival of several plant species, with
many under serious threats to become extinct. A holistic management action plan is
necessary to formulate for assessment and management of resource base; best
harvesting and processing practices; trade issues and aspects dealing with the
intellectual property rights on the traditional medicines by the tribal people.6
1.1.2 Steps necessary for promoting herbal drugs
Phytochemistry or natural product chemistry research is the backbone of herbal
industry. For promoting use of herbals in modern medicine, phytochemistry should be
envisaged for; isolation, purification and characterization of new phytoconstituents,
use of newly isolated phytoconstituents as “lead” compound for the synthetic design
of analogues with either improved therapeutic activity or reduced toxicity and
conservation of lead phytoconstituents into medicinally important drugs.7
1.1.3 Ethno-pharmacological approach to herbal drugs
The term ethno-pharmacology refers the interdisciplinary scientific observation,
description, and experimental investigation of indigenous drugs and biological
activities. Recent interest in the use of ethno-pharmacological information of plant
drugs has greatly increased for several reasons. Scientists showed that 119 important
plant derived drugs used in one or more countries, 88 were regarded as having been
discovered as a result of being derived from a plant used in traditional medicine.8
Chapter-1 INTRODUCTION
Bhavik Ph. D Dissertation 3
1.1.4 Practical aspects of herbal drug discovery
The stages involved in the development of pure drug from a plant source are
summarized as follow.
Collection and identification of the plant and deposition of voucher sample in
local and major herbaria.
Literature survey on the plant species selected for studies.
Preparation of extracts by using non-polar and polar solvent for initial
biological testing.
Evaluation of plant extract against a panel of biological test methods, as
exemplified by receptor biding, enzyme inhibition, and /or cytotoxicity assays.
Activity guided fractionation of the extract, by monitoring chromatographic
fraction with bioassay chosen from the panel available to the investigation.
Structure elucidation of pure active isolate using spectroscopic techniques and
chemical methods, if necessary.
Test each active compound (whether of novel or known chemical structure) in
all in vitro and in vivo biological test methods available, in order to determine
potency and selectivity of the drug.
Perform molecular modeling studies and prepare derivatives of the active
compound of interest.
Carry out large scale re-isolation of active compounds for toxicological,
pharmacological and mutation studies, when total synthesis is not practical.
Clinical trials (phase I – III).
1.1.5 Current status of herbal drugs
Recent years newer and newer diseases are posing threat to humanity. In fact diseases
are not new but are detected newly. Despite this, WHO had taken the vouch of
providing „Health for all‟ by 2000 AD. In spite of stupendous advances made by
modern medicine, the present century has many more health problems than earlier
centuries. Drugs for viral diseases like AIDS, certain type of cancers, arthritis,
Parkinsonism are yet to come. The newer concepts about herbal drugs have
immunomodulators and are recognized for prophylactic and preventive therapy.
Chapter-1 INTRODUCTION
Bhavik Ph. D Dissertation 4
Surprisingly, a recent survey revealed that more than 50% of all prescription drugs
issued by rational physicians are either directly derived from the natural sources or
synthesized from the natural models as the sole ingredient or as one of the several
ingredients. It seems certain that the continued scientific study of medicinal plants
afford a plethora of novel, structurally diverse and bioactive compounds.
Multidisciplinary research on plants has lead to many new drugs, as well as prototype
active molecules and biological tools.9
1.1.6 Future prospects in herbal medicines
At the moment, scientific research on medicinal plants is continuing most intensely in
research institutes, universities and pharmaceutical laboratories as well as in the
clinics of many developed countries. This research is oriented mainly in two
directions. Firstly the active ingredients of plants that have long been known for their
healing properties are been investigated. The second sphere of basic research has led
to the discovery of new kinds of medicinal plants and new drugs from the more
remote regions of the world where new species with unknown substances still remain
to be looked into.
Each and every traditional medicine are tested and validated scientifically. CSIR,
New Delhi, already involved in this filed, validated about 350 formulations for
different activities. The WHO has emphasized the need to ensure the quality control
of herbs and herbal formulations by using modern techniques. Several countries have
herbal pharmacopoeias and lay down monographs to maintain their quality. The
Ayurvedic pharmacopoeia of India which was recommends basic quality parameters
for eighty common Ayurvedic herbal drugs.10
1.2Standardization
Standardization is an essential factor for polyherbal formulation in order to assess the
quality of the drugs based on the concentration of their active principle. It is very
important to establish a system of standardization for every plant medicine in the
market, since the scope for variation in different batches of medicine is enormous.
Plant material when used in bulk quantity may vary in its chemical content and
therefore, in its therapeutic effect according to different batches of collection e.g.
collection in different seasons and/or from sites with different environmental
surroundings or geographical location. WHO has appreciated the importance of
Chapter-1 INTRODUCTION
Bhavik Ph. D Dissertation 5
medicinal plants for public health care in developing nations and has evolved
guidelines to support the member states in their efforts to formulate national policies
on traditional medicine and to study their potential usefulness including evaluation of
its quality, safety and efficacy.11
The process of evaluating the quality and purity of crude drugs by means of various
parameters like morphological, microscopically, physical, chemical and biological
observation is called standardization.12
Standardization involves adjusting the herbal drug preparation to a defined content of
a constituent or a group of substances with known therapeutic activity by adding
excipients or by mixing herbal drugs or herbal drug preparations. Botanical extracts
made directly from crude plant material show substantial variation in composition,
quality, and therapeutic effects. The presence of the word “Standardized” on a
supplement label does not necessarily indicate product quality. When the active
principles are unknown, marker substances should be established for analytical
purposes and standardization.
Fig 1.1: Parameters for standardization and quality evaluation of herbal drugs
1.2.1 WHO guidelines for standardization of herbal formulations.13,14
The standardization of crude drug materials includes the following steps
i. Authentication: Herbal drugs should be authenticated by considering
parameters like; stage of collection, parts of the plant collected, regional
status, botanical identity like phytomorphology, microscopy and
Chapter-1 INTRODUCTION
Bhavik Ph. D Dissertation 6
histological analysis, taxonomical identity, etc.
ii. Foreign matter: Herbs collected should be free from insect parts or
animal excreta and other contaminants like dust, soil, stones and
extraneous matter etc. Foreign matters also include parts or the organ of
the plant other than require for drug by definition or beyond limits set by
the WHO guidelines.
iii. Organoleptic evaluation: Sensory characters, taste, appearance, odour,
texture etc of the drug, are the various Organoleptic parameters should be
evaluated for identification and purity before undertaking further tests.
iv. Presence of important diagnostic tissues: Microscopically identity of
medicinal plant material is indispensable for the identification of broken
or powdered material. An examination by microscopy alone cannot
always provide complete identification, though when used in association
with other analytical method.
v. Ash values: The amount of material remaining after ignitionis called total
ash. It is also further determined by acid insoluble ash and water soluble
ash.
vi. Extractive values: This determines the amount of active constituents
extracted with different solvents like water, alcohol, ether, chloroform etc.
from a given amount of medicinal plant material.
vii. Moisture content and volatile matter: Determination of moisture
content or loss on drying helps in the estimation of the amount of volatile
matter. It is more appropriate for substances contain water as the only
volatile constituent. An excess of water in medicinal plant material will
encourage microbial growth so that limits for water content should be set
for every plants.
viii. Chromatographic and spectroscopic evaluation: TLC, HPTLC, HPLC
methods will provide qualitative and semi quantitative information about
the main active constituents present in the crude drug as chemical markers
in the TLC fingerprint evaluation of herbals. The quality of the drug can
also be assessed on the basis of the chromatographic fingerprint.
Chapter-1 INTRODUCTION
Bhavik Ph. D Dissertation 7
ix. Heavy metals: Medicinal plant materials with heavy metals like; arsenic,
lead, mercury and cadmium can be contaminated due to many causes
including environmental pollution and traces of pesticides.
x. Pesticide residue: WHO and Food and Agricultural Organization (FAO)
have set limits of pesticides, which are usually present in the herbs. These
pesticides are mixed with the herbs during the time of cultivation. Mainly
pesticides like DDT, BHC, toxaphene, and aldrin cause serious side-
effects in human beings if the crude drugs are mixed with these agents.
xi. Microbial contamination and afflatoxins: Usually medicinal plants
containing bacteria and molds are coming from soil and atmosphere.
Analysis of the limits of E. coli and molds clearly throws light towards the
harvesting and production practices. The substance known as afflatoxins
will produce serious side-effects if consumed along with the crude drugs.
Afflatoxins should be completely removed or should not be present.
xii. Radioactive contamination: Microbial growth in herbals is usually
avoided by irradiation. This process may sterilize the plant material but
the radioactivity hazard should be taken into account. The radioactivity of
the plant samples should be checked accordingly to the guidelines of
International Atomic Energy (IAE) in Vienna and that of the WHO.
In order to obtain quality oriented herbal products care should be taken right from the
proper identification of plants; season and area of collection, extraction, isolation and
verification process.
1.2.2 Quality control parameters for herbal formulations
i. Physical parameters: It include colour, appearance, odour, clarity,
viscosity, moisture content, ash values, pH, disintegration time, friability,
hardness, flow property, flocculation, sedimentation and settling rate.
ii. Chemical parameters: It includes limit tests for heavy metal, extractive
values, chemical assays for active constituents, etc.
iii. Chromatographic analysis of herbals: Chromatographic analysis can be
carried out using TLC, HPLC, HPTLC and GC, UV, Fluorimetry, GC-
MS, etc.
Chapter-1 INTRODUCTION
Bhavik Ph. D Dissertation 8
iv. Microbiological parameters: It includes total viable content, total mold
count, total entero-bacteriaceae and their count.
1.3Antioxidants15,16,17,18,19
Hyper physiological burden of free radical causes imbalance in homeostatic
phenomenon between oxidants and antioxidants in the body. The imbalance leads to
oxidative stress that is being suggested as the root cause of aging and various human
diseases like arteriosclerosis, stroke, diabetes, cancer and neurodegenerative diseases
such as Alzheimer‟s and Parkinsonism. Therefore research in recent past have
accumulated enormous evidence advocating enrichment of body system with
antioxidants to correct vitiated homeostasis and prevent onset as well as treat the
disease caused due to free radical and related oxidative stress. Stress, smoking, drugs
and dietgenerates excessive free radicals in human body.
Antioxidants have defined as the substance those in small quantities, able to prevent
or greatly retard oxidation of easily oxidisable material such as fats. Antioxidants may
exert their effect by different mechanisms such assuppressing the formation of active
species by reducing hyperoxides (ROO)and H2O2 and also by sequestering metal ions
scavenging active free radicals, repair and/or clearing damage. Mechanisms of radical
scavenging activity of antioxidants are well available
1.3.1 Characteristics
a) The presence of phenolic pharmacophore in antioxidant molecules.
b) An antioxidant should have electron-donating substituents.
c) Substitution on ortho positions are important in determining the stability of
phenoxy radical.
d) Presence of nucleophilic electron donating properties of polyphenols present in
the flavanol (tea) may be one of the important mechanisms of action involved in
inhibition of carcinogenesis.
Antioxidant plays an important role in removing such free radicals. Free radicals
reaction is an important pathway in a wide range of unrelated biological systems.
Amongst the many ways to chemically injure and kill cells, an important class of
reaction is that producing free radicals intermediates which trigger a network of
multifarious disturbances because of ubiquity of molecular oxygen in aerobic
organism and its ability to accept electron. Oxygen derived free radicals are often
mediators or products of normal pathological or toxic free radical reaction. A vast
Chapter-1 INTRODUCTION
Bhavik Ph. D Dissertation 9
number of circumstantial evidence implicates oxygen derived free radicals (especially
superoxide and hydroxyl free radical) and high-energy oxidants (such as
peroxynitrile) are as mediators of shock inflammation and ischemia reperfusion
injury. Thus, free radical scavenging is very essential for preventing organ injury
associated with shock, inflammation and ischemia reperfusion injury.
Naturally, there is a dynamic balance between the amount of free radicals generated in
the body and antioxidants to quench or scavenge them and protect the body against
their deleterious effects. However, the amount of free radicals protective antioxidant
principles present under normal physiological condition are only to cope with the
physiological role of free radical generation. Any addition burden of free radicals
eighter from environment or produced within the body, can tip the free radical (pro-
oxidant) and anti free radical (anti-oxidant) balance leading to oxidative stress, which
may result in tissue injury. These free radicals are chemical species possessing an
unpaired electron that can be considered as fragment of molecules and which are
generally extremely reactive and short lived. They are produced continuously in cells
eighter as accidental by products of metabolism or deliberately during phagocytises.
1.3.2Free radical’s formation
The haemolytic cleavage of a covalent bond of a normal molecule, with each
fragment retaining one of the paired electrons; by loss of single electron from a
normal molecule or by the addition of a single electron to a normal molecule. Electron
transfer is a far more common process in biological systems, than the other two. The
most important free radicals in biological systems are radical derivative of oxygen.
With increasing acceptance of free radicals as common and important bio-chemical
intermediates, they have been implicated in very large number of human diseases.
Thus free radical scavenging is very essential for preventing organ injury associated
with shock, inflammation and ischemia or reperfusion. Plants and its products are
known to possess excellent antioxidant properties and play a significant role in
preventing the conditions due to the excessive free radicals.
1.3.3In-vitro antioxidant assay method
Various antioxidant activity methods have been used to monitor and compare the
antioxidant activity of foods. These analytical methods measure the radical
scavenging activity of antioxidants against free radicals like DPPH, the hydroxyl
Chapter-1 INTRODUCTION
Bhavik Ph. D Dissertation 10
radical or the Peroxyl radical (ROO), superoxide anion radicalO2. The various
methods used to measure the antioxidant activity of various extracts can give varying
results depending on the specificity of the free radical being used as reactant. The
following reactants are being used to determine the antioxidant activity.
a. Malondialdehyde (MDA)
b. Thiobarbituric acid-reactive substances(TBARS)
c. 2,2-aznobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS)
d. 2,2-azobis(2-amidinopropane)(AAPH)
Many studies have been performed to identify anti-oxidant compounds with
pharmacological activity and a limited toxicity. The phytochemical analysis of plants
used traditionally has revealed a large number of compounds including flavonoids,
vitamins, carotenoidsand polyphenols, which have been proved to have potent anti-
oxidant properties. The herbal mixture preparations of Indian traditional medicines
have also anti-oxidant activity arising from their content of plants with antioxidant
principles that act probably in a synergistic way. This hypothesis along with the lack
of toxicity can be important to understand their use in past as well as now a day.
Based on the concept, present study was undertaken to evaluate the antioxidant
potentials of Bhunimbadi churna, which has been explored for their antioxidant
potential through various in vitro models.
A general recommendation to the consumer is to increase the intake of foods rich in
anti-oxidant compounds having well-known healthy effects. As a consequence, these
evidences accelerated the search for antioxidants principles, which led to the
identification of natural re-sources and isolation of active antioxidant molecules.
Plants with potential antioxidant activities are given in Table 1.1
Table 1.1: Medicinal plants with antioxidant properties20,21,22
Sr No. Botanical name Family Part used
1 Achilleamillefolium Asteraceae Whole plant
2 Acoruscalamus Araceae Rhizome
3 Archangelicaofficinalis Umbelliferae Leaf
4 Artemisia vulgaris Compositae Whole plant
5 Carumcarvi Umbelliferae Fruit
6 Chelidoniummajus Papaveraceae Whole plant
Chapter-1 INTRODUCTION
Bhavik Ph. D Dissertation 11
7 Curcuma longa Zingiberaceae Rhizome
8 Cynamonumzeylanicum Lauraceae Seed
9 Cyperusrotundus Cyperaceae Root, Stem
10 Echinacea purpurea Asteraceae Leaf
11 Epilobiumhirsutum Onagraceae Whole plant
12 Glycyrrhiza glabra Fabaceae Stem
13 Herniaraglebra Caryophyllaceae Whole plant
14 Holarrhenaantidysenterica Apocynaceae Seed, stbk
15 Humuluslupulus Cannabaceae Cone
16 Hypericumperforatum Hypericaceae Whole plant
17 Inulahelenium Compositae Root
18 Juglansregia Juglandaceae Leaf
19 Levisticumofficinale Umbelliferae Whole plant
20 Marrubiumvulgare Labiatae Whole plant
21 Melisa officinalis Labiatae Whole plant
22 Myristicafragrans Myristicaceae Fruit
23 Origanumvulgare Labiatae Whole plant
24 Petroselinumsativum Umbelliferae Root
25 Picrorrhizakurroa Scrophulariaceae. Rhizome
26 Piper longum Piperaceae Fruit
27 Piper nigrum Piperaceae Fruit
28 Plumbagozeylanica Plumbaginaceae Root
29 Polygonumaviculare Polygonaceae Whole plant
30 Salvia officinalis Labiatae Whole plant
31 Silybummarianum Compositae Seed
32 Swertiachirata Gentianaceae Whole plant
33 Syzygiumaromaticum Myrtaceae Fruit
34 Thymus vulgaris Lamiaceae Leaf
35 Valerianaofficinalis Valerianaceae Root
36 Zingiberofficinale Zingiberaceae Rhizome
Chapter-1 INTRODUCTION
Bhavik Ph. D Dissertation 12
1.4 Diabetes
There are many diseases that are caused due to genetically disorders, and one of this is
Diabetes Mellitus. Diabetes is a disorder of metabolism (the way our bodies use
digested food for growth and energy). Most of the food we eat is broken-down by the
digestive juices into a simple sugar called glucose. Glucose is the main source of fuel
for the body. After digestion, the glucose passes into bloodstream where it is available
for body cells to use for growth and energy. Glucose gets into the cells in presence of
insulin, a hormone produced by the pancreas.
Normally, pancreas is automatically producing the right amount of insulin to move
the glucose from our blood into our cells. If body doesn‟t make enough insulin or the
insulin doesn't work right, the sugar cannot get into the cells. It stays in the blood.
This makes high levels of glucose (or sugar) in the blood producing hyperglycemia.
As a result, glucose builds up in the blood, overflows into the urine, and passes out of
the body in urine (glucosuria). Thus, the body loses its main source of fuel even
though the blood contains large amounts of glucose. Thus Diabetes is a chronic
condition that occurs when the pancreas does not produce enough insulin or when the
body cannot effectively use the insulin.23,24
There are more than 125 million people with diabetes in the world today and this
number is expected to approach 220 million. It is also estimated that there are 30 to 33
million diabetics in India now, and every fourth diabetics in the world today is an
Indian. Indians are genetically more susceptible to diabetes and the WHO predicts the
number of diabetes in India would group to 80 million by 203025
.There are two types
of Diabetes; Diabetes insipidus and Diabetes mellitus.
1.4.1 Diabetes Insipidus: Despite the similar names diabetes insipidus is not related
to diabetes mellitus. Some people with diabetes insipidus have kidneys that don‟t
concentrate urine very well (meaning their urine is more diluted). They might wake
up 2 or 3 times in the night to urinate. People with diabetes insipidus are thirsty all the
time. They often want to drink liquids every hour.
Etiology of Diabetes insipidus suggests that in some people, a part of the brain
doesn‟t make enough anti diuretic hormone (ADH).In other people, the kidneys do
not work with this hormone the way they should. Most people with diabetes insipidus
get it after an injury to the head or after brain surgery or in case of a brain tumor.26
Chapter-1 INTRODUCTION
Bhavik Ph. D Dissertation 13
1.4.2 Diabetes mellitus: It is a clinical syndrome characterized by hyperglycemia due
to the pancreas may produce little insulin, if any. In other cases, the pancreas may
produce some insulin, but the cells do not respond to it. Diabetes mellitus is
characterized by hyperglycemia, glucosuria, negative nitrogen balance and sometimes
ketonemia.27
It is classified as follows
Type I: Immune mediated - Juvenile onset /Insulin dependent (could be in
children with a more rapid onset or adults with a slower onset „late
autoimmune diabetes of adults‟),
Type II: Insulin resistant -Adult onset diabetes/non-insulin dependent diabetes
A. Gestational diabetes mellitus
B. Other specific types (e.g. certain genetic defects; drug induced; etc)28
Type I: It is characterized by severe lack of insulin due to the destruction of most or
all of the beta cells in the islets of Langerhans by an autoimmune process, usually
leading to absolute insulin deficiency. The onset is usually acute, developing over a
period of a few days to weeks. Over 95% of persons with type 1 diabetes mellitus
develop the disease before the age of 25 and most often between the ages of 10 and
16, with an equal incidence in both sexes and an increased prevalence in the white
population. Type I diabetes is invariably treated with insulin.
Type II: Insulin resistance in peripheral tissue and an insulin secretary defect of the
beta cell of pancreas, so that less glucose is produced, and to an impairment of
insulin's ability to stimulate the uptake of glucose in muscles and other tissues. The
cause of this insulin resistance has not yet been fully established, but may involve
defects in the action of insulin after it has bound to the insulin receptor on the surface
of cells. This is the most common form of diabetes mellitus and is highly associated
with a family history of diabetes, older age, obesity and lack of exercise.29,30
A. Gestational diabetes: Occur during pregnancy, sensitivity to insulin
decreases (placental hormones affect glucose tolerance). Beta cells may not be
able to meet this increased need for insulin gestational diabetes. They are
occurs in up to 14% of pregnancy. This increases subsequent risk of
developing type II diabetes. Increased risk for perinatal mortality and neonatal
morbidity.
Chapter-1 INTRODUCTION
Bhavik Ph. D Dissertation 14
B. Other types of diabetes mellitus: Specific genetic/molecular defects have
been identified in a minority of what were considered type II diabetes:
1) Genetic defects of function of beta cell. e.g. Hepatic nuclear factor 4
alpha - autosomal dominant condition of impaired insulin secretion;
early onset and slowly progressive; type I(mature onset diabetes of the
young).e.g. Mutation of mitochondrial DNA
2) Genetic defects in the action of insulin: e.g. insulin receptor - (severe
insulin resistance) Lipoatrophic diabetes
3) Endocrine disorders
Diseases of the pancreas, e.g. pancreatitis, neoplasia, cystic
fibrosis, haemochromatosis
Endocrinopathies, e.g. acromegaly, Cushing's syndrome,
hyperthyroidism, pheochromocytoma
4) Drug/chemical induced, e.g. vacor, pentamidine, glucocorticoids,
thiazides, dilantin
5) Infection, e.g. congenital rubella, cytomegalo virus
6) Immune mediated (uncommon), e.g. Stiff man syndrome, anti-insulin
receptor antibodies.
1.4.3 Causes of Diabetes
a. Heredity i.e. family history of late onset diabetes
b. Obesity i.e. over weight
c. Lack of physical activity i.e. sedentary life style
d. Women with prior gestational diabetes
e. Stress and Strain31
1.4.4 Diabetes Symptom
A. Symptoms of type I diabetes may include
Increased thirst and urination
Blurred vision
Feeling very hungry
Weight loss in spite of increased eating
Chapter-1 INTRODUCTION
Bhavik Ph. D Dissertation 15
B. Symptoms of type II diabetes may include
Feeling tired or ill
Frequent urination (especially at night)
Unusual thirst
Weight loss
Blurred vision
Frequent infections
Slow healing of sores.
Having dry, itchy skin
Having tingling in the feet.
1.4.5 Complications occur in diabetes
Acute Complications
Type – I Diabetes (IDDM)
Due to illness or fever, insulin requirement increases if additional requirement
of insulin is not met with, a diabetic coma can develop.
Diabetic Ketoacidosis – Appearance of large amount of glucose along with
„Ketone‟ bodies in urine.
Type – II Diabetes (NIDDM)
Dehydration coma – Loss of excessive amounts of water and salt.
Skin problems.
Long term complications
Eyes: Progressive loss of vision, leading to blindness, diabetes is among the
three common causes of blindness today.
Heart: Diabetics are very prone to developing high blood pressure.
Blood vessels and circulation: The arteries may develop fat deposits
hindering flow of blood, affecting the blood supply to extreme parts of limbs.
An injury of such limbs may develop gangrene, which may lead to an
amputation.
Chapter-1 INTRODUCTION
Bhavik Ph. D Dissertation 16
Kidneys: More susceptible to infections of the urinary bladder and Kidneys. It
may also lead to failure of kidney functions.
Nervous System: Diabetes affects the nerves leading to loss of sensation. In
contrast certain diabetics may suffer from tingling or burning sensation in
extreme parts of limbs.32
1.4.6 Prevention of diabetes mellitus
It may not be possible to prevent diabetes in all cases but even delay in its onset is an
achievement. First step is the identification of high-risk groups. These high-risk
individuals follow.
Regular exercise to maintain normal body weight
Obese persons should undergo diet control and exercise to reduce weight.
Avoid fast food and take original Indian lacto vegetarian food
Avoid stressful life.
Meditation and yoga can also help.
Two diabetics should not marry.
If above non-pharmacological methods fail drugs may be used for prevention of
diabetes.33
1.4.7 Drug used in diabetes
Oral Hypoglycemic agents
1) Sulphonylureas : Gibenclamide, Tolbutamide,
Chlorpropamide, Tolazamide,
Glipizide, Gliclazide
2) Bigaunides : Metformin,Phenformin
3) α-Glucosidase inhibitors : Acarbose, Miglitol, Voglibose
4)Thiozolindinedione derivatives : Troglitazone, Ciglitazone
5) Inhibitors or gluconeogenesis : Dichloroacetic acid (DCA)
6) Inhibitors of lypolysis : Acipimox (Nicotinic acid analogue)
7) Fatty acid oxidation : Tetrahydecylglycidicacid (TDGA)
Chapter-1 INTRODUCTION
Bhavik Ph. D Dissertation 17
Oral anti-diabetic agents, act only on a part of the pathogenic process, may not
produce any cure and prevent all the complications of diabetes. Insulin cannot be used
orally and continuous insulin injection has many side effects and toxicity. Thus,
people have started looking at the ancient healing systems. Since ancient times many
medicinal plants claim to control the diabetes in humans but systematic evaluation of
them are not done yet. The lack of documentation and stringent quality control are the
key obstacles, have hindered the acceptance of the alternative medicines in the
developed countries. In recent times, many studies have been carried out in the search
of a proper plant drug that would be effective in diabetes mellitus. Medicinal plants
with proven antidiabetic and related beneficial effects used in treatment of diabetes
are compiled in table 1.2.
Table 1.2: Medicinal plants with antidiabetic properties34,35,36
Sr No. Botanical name Family Part used
1 Acacia Arabica Mimosaceae Bark
2 Acacia malanoxylon Fabaceae Root
3 Acacia modesta Fabaceae Seed
4 Adhatodavasica Acanthaceae Leaves
5 Aeglemarmelos Rutaceae Leaves & Root
6 AlangiumSalvifolium Alangiaceae Leaves
7 Allium cepa Liliaceae Bulb
8 Alliumsativum Liliaceae Bulb
9 Aloe barbadensis Liliaceae Leaves
10 Anacardiumoccidentale Anacradiaceae Leaves & bark
11 Areca catechu Arecaceae Seed
12 Artemisia pallens Compositae Arial parts
13 Avena sativa Cyperaceae Seed
14 Azadirachtaindica Meliaceae Leaves
15 Boerhaviadiffusa Nyctaginaceae Leaves
16 Bougainvillea pectabilis Nyctaginaceae Leaves
17 Brassica oleracea Brassicaceae Leaves
18 Cassia fistula Leguminoseae Seeds
19 Cassia occidentalis Febaceae Seed & Bark
Chapter-1 INTRODUCTION
Bhavik Ph. D Dissertation 18
20 Cocciniaindica Cucurbitaceae Root
21 Cyperusrotundus Cyperaceae. Rhizome
22 Emblicaofficinalis Myrtaceae Seed
23 Eucalyptus citriodora Myrtaceae Leaves
24 Eugenia jambolana Myrtaceae Seed
25 Ficusreligiosa Moraceae Bark & Root
26 Gmelina arborea Verbenaceae Fruit
27 Gymnemasylvestre Asclepiadaceae Leaves
28 Holarrhenaantidysenterica Apocynaceae Seed
29 Holarrhenaantidysenterica Apocynaceae Stem Bark
30 Holostemaannualare Asclepiadaceae Root
31 Hordeumvulgare Gramineae Root
32 Ipomoea nil Convolvulaceae Whole plant
33 Mangiferaindica Anacardiaceae Leaves
34 Momordicacharantia Cucurbitaceae Fruits
35 Morus alba Moraceae Leaves
36 Picrorhizakurroa Scrophulariaceae Rhizome
37 Piper nigrum Piperaceae Fruit
38 Piper longum Piperaceae Fruit
39 Pinusroxburghii Pinaceae Bark & Root
40 Plumbagozeylanica Plumbaginaceae Root
41 Pterocarpusmarsupium Leguminoseae Bark &Wood
42 Saussurealappa Compositae Root
43 Swertiachirata Gentianaceae Whole plant
44 Smilax lanceifolia Smilacaceae Root
45 Trigonellafoenum-graecum Leguminoseae Seed
46 Thevetiaperuviana Apocynaceae Bark
47 Zanthoxylumacanthopodium Rutaceae Leaf
48 Zingiberofficinale Zingiberaceae Rhizome
Chapter-1 INTRODUCTION
Bhavik Ph. D Dissertation 19
Marker compound, chemical constituents within a medicinal that can be used to verify
its potency, isolated for direct use as drugs and lead compounds or pharmacological
agents.Here given some active agents isolation from medicinal plants used as an
antidiabetic agent are given in table 1.3.
Table 1.3: Active antidiabetic principles isolated from the medicinal plants37,38
Sr. No Botanical name Part used Active Principles (Marker)
1 Acontiumcarmichaeii Root Aconitan A,B,C &D
2 Anemarans Rhizomes Anemarans A, B, C&D
3 Atractylodes japonica Rhizome Glycons A,B,C,D Atractants
4 Bauhinia pururea Aerial part Quercetin
5 Capsicum annum Fruit Capsaicin
6 Clytiarichardiana Leaves SaudinRhamnoside
7 Cyperusrotundus Rhizome Cyperene
8 Dioscorea japonica Rhizome Glycans A,B,C,D,E,F
9 Galegaofficinalis Seed Galegin
10 Holarrhenaantidysenterica Seed Conessine
11 Holarrhenaantidysenterica Stem Bark Conessine
12 Lathyrus japonica Seed Lathyrines
13 Lepidiumruderale Aerial part Lepidine
14 Picrorhizakurroa Rhizome Picroside I, II
15 Piper nigrum Fruit Piperin
16 Piper longum Fruit Piperin
17 Potatorumancisteroides Aerial part Tormetic acid
18 Plumbagozeylanica Root Plumbagin
19 Swertiachirata Whole plant Sawertiamarine, Mangeferin
20 Zingiberofficinale Rhizome 6,8,10-gingerol
Chapter-1 INTRODUCTION
Bhavik Ph. D Dissertation 20
References
1 Sujatha S, ShalinJJ.Complementary therapeutic potential: A focus on polyherbal
products for hyperglycemia. Asian J Scientific Res 2012; 5(1):1-13.
2 Kokate CK, Purohit AP, Gokhale SB. Textbook of
Pharmacognosy.14thedition.NiraliPrakashan, Pune 2000:1-4.
3 Shastri MR. Legal regulatory control on herbal drugs.The Eastern Pharmacist
1993: 49-53.
4 HandaSS.Future trends of plants as drugs. Pharma Times 1991; 23(4):13.
5 Tewari DN.Report of the task force on conservation & sustainable use
ofmedicinalplants.Available from:
http://planningcommission.nic.in/aboutus/taskforce/tsk_medi.pdf.
6 Seth SD, Sharma B. Medicinal plants in India. Indian J of Med Res 2004;
120(1): 9-11.
7 Graham NA, Chandler RF. Podophyllum. Canad Pharm J 1990; 123:330-33.
8 De Smet PAGM, Rivier L. A general outlook on ethanopharmacology.J of
Ethnopharmacology1989; 25: 127-38.
9 Ashok DB, Thomas PA. Current status of herbal drugs in India: An overview. J
ClinBiochemNutr 2007; 41:1-11.
10 Dobriyal RM, Narayana BA. Ayurvedic herbal raw material.The Eastern
Pharmacist 1998; 31-2.
11 Aswatha Ram HN, Ujjwal K, Lachake P, Shreedhara CS. Standardisation of
Avipattikarchurna-apolyherbal formulation. Pharmacognosy Research 2009;
1(4):224-27.
12 Agrawal SS,Tamrakar BP, Paridhavi M.Clinically useful Herbal Drugs. 1st
edition, Ahuza publishing house 2005:193-97.
13 Quality controls methods for medicinal plant materials. World Health
Organization, Geneva. AITBS publisher and distributors, Delhi 2002: 8-70.
14 http://www.pharmainfo.net/reviews/who-guidelines-herbal-drugs.
Chapter-1 INTRODUCTION
Bhavik Ph. D Dissertation 21
15 Viturro C, Molina A, Schmeda G. Free radical scavengers from
Mutsiafriesiana(Asteraceae) and Saniculagraveoleans (Apiaceae).
Phytotherapy Res 1999; 13(5):416-18.
16 Devaki T, Shivshangari KS, Govindraju P. Effect of Boerhhaviadiffusaon tissue
antioxidant defence system during ethanol induced hepatotoxicity in rats. J Nat
Remed2005; 5(2):102-7.
17 Kelm MA, Nair MG, Strasberg GM. Antioxidant and cycloxygenase inhibitory
phenollic compounds from Ocimum sanctum Linn. Phytomedicine2000; 7(1):
7-13.
18 Shenoy R, Shirwaikar A. Anti-inflammatory and free radical scavenging studies
of Hyptissuaveolens(Labiatae). Indian drugs 2002; 39(11): 574-77.
19 Baheti JR, Jain V, Shah GB, Goyal RK. Free radical scavenging activity of
aqueousextract of Rhussuccendaneagalls. J Nat Remed2005; 5(1):15-18.
20 Wojdylo A, ski JO, Czemerys R. Antioxidant activity and phenolic compounds
in 32 selected herbs. Food Chemistry 2007;105: 940-49.
21 Katalinic V, Milos M, Kulisic T. Screening of 70 medicinal plant extracts for
antioxidant capacity and total phenols.Food Chemistry 2006; 94: 550-57.
22 Dragland S, Senoo H, Wake K, Holte K, Blomhoff R. Several culinary and
medicinal herbs are important sources of dietary antioxidants. J of Nutrition
2003; 133:1286–90.
23 Elsas JL, Longo N.Glucose Transporters. Annual Review of Medicine 1992;
43:377-93.
24 http://www.diabetes .niddk.nih.gov
25 http://www.who.int.
26 http://www.ctfp.com/pt_out/Diabetes%20Insipidus.doc
27 Tripathi KD. Essentials of Medical Pharmacology.5th edition, Jaypee
brothers, New Delhi 2003:242-43.
28 Pickup JC.Text Book of Diabetes.2nd
edition. Black Well Scientific
Publications, London 1991; (2): 4-9.
Chapter-1 INTRODUCTION
Bhavik Ph. D Dissertation 22
29 http://www.ultimatefatburner.com/introduction-to-diabetes.html.
30 Rang HP, Dale MM, Ritter JM, Moor PK. Book Review: Pharmacology.5th
edition. Elsevier, New Delhi 2003: 385-87.
31 http://diabetesinformationhub.com/WhatCausesDiabetes.php.
32 http://www.holisticonline.com/Remedies/Diabetes/diabetes_introduction.htm
33 http://www.medicinenet.com/diabetes_prevention/article.htm.
34 Mukherjee PK, Maiti K, Mukherjee K. Leads from Indian medicinal plants with
hypoglycemic potentials.J Ethnopharmacol2006; 106: 1-28.
35 Arumugam G, Manjula P, Paari N. A review: Anti diabetic medicinal plants
used for diabetes mellitus. J Acute Disease 2013:196-200.
36 Chauhan A, Sharma PK, Srivastava P, Kumar N.Plants having potential
antidiabetic activity: A review.Der Pharmacia Letter2010;2(3):369-87.
37 Hakin ZS. Potential antidiabetic agents from plant sources- pharmacological
aspects.Ind J Nat Prod 1995; 11(1):3.
38 Mrles RJ, Frnsworth NR. Antidiabetic plants and their active
constituents.Phytomedicine 1995; 2(2):137-89.