Diabetes mellitus: An overview on its pharmacological aspects and reported medicinal plants having antidiabetic activity

Abstract

Diabetes mellitus is not a single disease but is a group of metabolic disorders affecting a huge number of population in the world. It is mainly characterized by chronic hyperglycemia, resulting from defects in insulin secretion or insulin action. It is predicated that the number of diabetes person in the world could reach upto 366 million by the year 2030. Even though the cases of diabetes are increasing day by day, except insulin and oral hypoglycemic drugs no other way of treatment has been successfully developed so far. Thus, the objective of the present review is to provide an insight over the pathophysiological and etiological aspects of diabetes mellitus along with the remedies available for this metabolic disorder. The review also contains brief idea about diabetes mellitus and the experimental screening model with their relevant mechanism and significance mainly used nowadays. Alloxan and streptozotocin are mainly used for evaluating the antidiabetic activity of a particular drug. This review contain list of medicinal plants which have been tested for their antidiabetic activity in the alloxan induced diabetic rat model. From the available data in the literature, it was found that plant having antidiabetic activity is mainly due to the presence of the secondary metabolite. Thus, the information provided in this review will help the researchers for the development of an alternative methods rather than insulin and oral hypoglycemic agents for the treatment of diabetes mellitus, which will minimize the complication associated with the diabetes and related disorder.

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Document heading
Diabetes mellitus: An overview on its pharmacological aspects and
reported medicinal plants having antidiabetic activity
Patel DK, Kumar R, Laloo D, Hemalatha S*
Pharmacognosy Research Laboratory, Department of Pharmaceutics, Institute of Technology, Banaras Hindu University, Varanasi-221005, India
Asian Pacific Journal of Tropical Biomedcine (2012)411-420
Asian Pacific Journal of Tropical Biomedicine
journal homepage:www.elsevier.com/locate/apjtb
*Corresponding author: Hemalatha S, Pharmacognosy Research Laboratory,
Department of Pharmaceutics, Institute of Technology, Banaras Hindu University,
Varanasi-221005, India.
Tel: + 91 9415256481
E-mail: shemalatha.phe@itbhu.ac.in
1. Introduction
Diabetes is a metabolic disorder of carbohydrate, fat
and protein, affecting a large number of population in
the world[1]. Diabetes mellitus is not a single disorder
but it is a group of metabolic disorder characterised by
chronic hyperglycemia, resulting from defects in insulin
secretion, insulin action, or both. Increased thirst, increased
urinary output, ketonemia and ketonuria are the common
symptoms of diabetes mellitus, which occur due to the
abnormalities in carbohydrate, fat, and protein metabolism.
When ketones body is present in the blood or urine, it
is called ketoacidosis, hence proper treatment should
be taken immediately, else it can leads to other diabetic
complications[2]. Diabetes mellitus has caused significant
morbidity and mortality due to microvascular (retinopathy,
neuropathy, and nephropathy) and macrovascular
(heart attack, stroke and peripheral vascular disease)
complications[3]. Diabetes is mainly attributed to the
rapid rise in unhealthy life style, urbanization and aging.
Hyperglycaemia which is the main symptom of diabetes
mellitus generates reactive oxygen species (ROS) which
cause lipid peroxidation and membrane damage. ROS
plays an important role in the development of secondary
complications in diabetes mellitus such as cataract,
neuropathy and nephropathy. Antioxidants protect 毬-cells
from oxidation by inhibiting the peroxidation chain reaction
and thus they play an important role in the diabetes. Plants
containing natural antioxidants such as tannins, flavonoids,
vitamin C and E can preserve 毬-cell function and prevent
diabetes induced ROS formation. Polyphenols, which are
classified into many groups such as flavonoids, tannins and
stilbenes, have been known as health-beneficial properties,
which include free radical scavenging, inhibition of
hydrolytic and oxidative enzymes, anti-inflammatory action
and antidiabetogenic potentiality[4,5]. Aldose reductase as
a key enzyme, catalyze the reduction of glucose to sorbitol
and is associated in the chronic complications of diabetes
ART ICLE IN FO ABSTR ACT
Article history:
Received 4 April 2011
Received in revised form 27 July 2011
Accepted 3 September 2011
Available online 28 May 2012
Keywords:
Aldose reductase
Alloxan
Antioxidant
Diabetes mellitus
Insulin
Phytoconstituents
Streptozotocin
Oral hypoglycemic agents
Diabetes mellitus is not a single disease but is a group of metabolic disorders affecting a huge
number of population in the world. It is mainly characterized by chronic hyperglycemia, resulting
from defects in insulin secretion or insulin action. It is predicated that the number of diabetes
person in the world could reach upto 366 million by the year 2030. Even though the cases of
diabetes are increasing day by day, except insulin and oral hypoglycemic drugs no other way of
treatment has been successfully developed so far. Thus, the objective of the present review is to
provide an insight over the pathophysiological and etiological aspects of diabetes mellitus along
with the remedies available for this metabolic disorder. The review also contains brief idea about
diabetes mellitus and the experimental screening model with their relevant mechanism and
significance mainly used nowadays. Alloxan and streptozotocin are mainly used for evaluating the
antidiabetic activity of a particular drug. This review contain list of medicinal plants which have
been tested for their antidiabetic activity in the alloxan induced diabetic rat model. From the
available data in the literature, it was found that plant having antidiabetic activity is mainly due
to the presence of the secondary metabolite. Thus, the information provided in this review will
help the researchers for the development of an alternative methods rather than insulin and oral
hypoglycemic agents for the treatment of diabetes mellitus, which will minimize the complication
associated with the diabetes and related disorder.
Contents lists available at ScienceDirect

Patel DK et al./Asian Paicfic Journal of Tropical Biomedicine (2012)411-420
412
such as peripheral neuropathy and retinopathy. Use of aldose
reductase inhibitors and 毩-glucosidase inhibitors has been
reported for the treatment of diabetic complications[6].
The aim of this review is to provide the available data
about diabetes mellitus, its epidemiology, causes of diabetes,
pathophysiology, available treatment, diagnostic criteria,
major available screening model system, herbal approach to
treat diabetes and pharmacologically tested plant material.
The review also covers certain plant materials which were
screened in alloxan induced diabetic rat’s models and the
data information were collected from the available litreature
search published in last three year using alloxan induced
diabetic rat model. Moreover, only subacute and chronic
diabetic study of the plant material were included in the
present review.
2. Epidemiology of diabetes mellitus
The word ‘diabetes’ is derived from the Greek word “Diab”
(meaning to pass through, referring to the cycle of heavy
thirst and frequent urination); ‘mellitus’ is the Latin word for
“sweetened with honey” (refers to the presence of sugar in
the urine). Greeks had knowledge of a disease accompanied
by polyurea and wasting of body, whereas Aretaeus of
Cappadocia mentioned a disease characterized by thirst
and polyurea. Subsequently, the knowledge spreaded to
Chinese, Iranians and Arabians. From the Middle East, the
knowledge of diabetes mellitus had spread to Spain as a
disease characterized by polyurea, polydipsia with sugary
flavoured urine. With the discovery of sugar in urine and its
detection by laboratory test, the knowledge permeated into
the 18th century. The estimated burden of diabetes in India
was 22 millions in 1990, 28 million in 1995 and 33 millions in
2000. It is the most common metabolic associated disease
in the world. NIDDM is the most common form of diabetes
constituting nearly 90% of the diabetic population in any
country with varying numbers in different geographical
regions[7].
According to ancient Hindu physicians, ‘Madhumeha’
is a disease in which a patient passes sweet urine and
exhibits sweetness all over the body. They had recorded in
their observations that ‘if too many ants swarm around a
spot of urine, then the person have symptoms of diabetes
mellitus’[7]. According to World Health Organization
projection, the diabetes population is likely to increase to
300 million or more by the year 2025[8]. The current studies
in India indicate that there is an alarming rise in prevalence
of diabetes which has gone beyond epidemic form to a
pandemic one[1]. Globally, diabetes mellitus presents
enormous and increasingly important public health issues.
The occurrence and consequences associated with diabetes
are found to be high in countries like India (31.7%), China
(20.8%) and United State of America (17.7%)[9]. It is predicted
that by 2030, India, China and the United States will have
the largest number of people with diabetes[10]. In most
western countries, type 1 diabetes accounts for over 90% of
childhood and adolescent diabetes although less than half
of individuals with type 1 diabetes are diagnosed before the
age of 15 years. Type 2 diabetes is becoming more common
in youth onset diabetes in certain at risk populations. In
addition, there is a distinct slowly progressive form of type 1
diabetes in Japan, which represents approximately one third
of cases of type 1 diabetes. Type 1 diabetes is more common
in the offspring of diabetic men compared with diabetic
women[2].
3. Type of diabetes mellitus
Based upon the etiology, diabetes mellitus can be divided
into two main types, Type 1, “Juvenile Diabetes Mellitus”
(Insulin Dependent Diabetes Mellitus) and Type 2, “Adult
type” (Non-Insulin Dependent Diabetes Mellitus). Type 1
occurs in childhood, mainly due to destruction of pancreatic
毬-cell islets through autoimmune-mediated, resulting in
absolute insulin deficiency. Type 2 is more associated with
an adulthood and elderly people, which are mainly due to
insulin resistance or abnormal insulin secretion[3,7]. The
exact causes of pancreatic failure and insulin resistance
are unknown, but they are associated with disease state,
environmental impact and food habit. Diabetic patients
are more susceptible to various type of infection such as
skin diseases and carbuncles[7]. Other type of diabetes
is gestational diabetes which is mainly associated with
pregnancy. Genetic defects of 毬-cell function or insulin
action is also a type of diabetes mellitus commonly called
maturity onset diabetes[2]. Neonatal diabetes mellitus is
also a type of disorder in which Insulin is required for
the maintainance of blood glucose level in the first three
months of life. It may be associated with intrauterine growth
retardation and defects of chromosome[2]. Mitochondrial
diabetes is commonly associated with sensorineural deafness
and is characterised by progressive non-autoimmune beta-
cell failure[2]. Cystic fibrosis related diabetes is primarily
due to insulin deficiency, but insulin resistance during
acute illness, secondary to infections and medications,
may also contribute to impaired glucose tolerance and
diabetes. Sometimes diabetes can also occurs by other
factors like stress or in other case by the uses of medication
such as dexamethasone, L-asparaginase, glucocorticoids,
cyclosporin or tacrolimus, olanzapine, risperidol, quetiapine
and ziprasidone[2].
4. Pathophysiology of diabetes mellitus
Diabetes mellitus has a profound adverse effect on quality
of life in terms of social, psychological well-being as well as
physical health. Diabetic complications are mainly mediated
through oxidative stress such as increased production of
ROS or impaired antioxidant defense systems. Enhancement
of lipid peroxidation, alteration in antioxidant enzymes
and impaired glutathione metabolism are the main factors

Patel DK et al./Asian Paicfic Journal of Tropical Biomedicine (2012)411-420 413
involved in the development of diabetes[11]. Production of
free radicals is also involved in the pathogenesis of various
type of disease including diabetes mellitus[12]. Increased
formation and accumulation of advanced glycation products
(AGEs) is also involved in the diabetic complications,
such as retinopathy, neuropathy, and renal dysfunction
through a series of pathological changes[13]. Though several
hormones are involved in the regulation of blood glucose
level, the most important ones are insulin and glucagon.
When imbalanced occurs in the level of hormones in the
body, sugar starts accumulating in the blood and when
concentration of glucone increased in the blood then finally
it will passes in urine along with other minerals[7]. In most
cases of diabetes, primarily T-cell mediates pancreatic islet
毬-cell destruction, and becomes clinically symptomatic
when 90% of pancreatic beta cells are destroyed. Serological
markers such as islet cell, glutamic acid decarboxylase
(GAD), IA-2, IA- 2毬, or insulin autoantibodies, are present
in 85-90% of individuals when fasting hyperglycemia
is detected. Sometimes environmental triggers, such as
chemical or viral initiated pancreatic 毬-cell destruction,
which can triger consequences and thereby leads to the
cause in diabetes mellitus. From the study it was found that
enterovirus infection is also associated with the development
of diabetes mellitus[2].
5. Causes of diabetes mellitus
The cause of diabetes depends on the type of diabetes.
Type 1 occurs mainly due to 毬-cell destruction, mediated
through either immune mediated or idiopathic, whereas
Type 2 diabetes occurs mainly due to insulin resistance or
with relative insulin deficiency. Diabetes is also associated
with lifestyle factors and genetics[2]. There are various types
of other factors that involved in the development of diabetes
which are the genetic material such as chromosomal and
mitochondrial DNA mutation. Leprechaunism, Rabson-
Mendenhall syndrome and lipoatrophic diabetes is
associated with the genetic defects in insulin action.
In some cases congenital rubella and cytomegalovirus
infection also lead to the cause of diabetes mellitus.
Sometimes drugs and other chemicals such as pentamidine,
nicotinic acid, glucocorticoids, thyroid hormone, 毬
-adrenergic agonists, thiazides, 毩-interferon can cause
diabetes mellitus. Abnormalities in the pancrease such as
pancreatitis, pancreatectomy, neoplasia, cystic fibrosis,
fibrocalculous pancreatopathy can also develop diabetes.
There are other factors related to immune system such as
‘Stiff-man’ syndrome and anti-insulin receptor antibodies
that are involved in the development of the diabetes.
Disease associated with pancrease such as aromegaly,
Cushing’s syndrome, glucagonoma, phaeochromocytoma,
hyperthyroidism and aldosteronoma can also mediate
diabete mellitus. There are some other genetic syndromes
such as Down syndrome, Klinefelter syndrome, Turner
syndrome, Wolfram syndrome, Friedreich’s ataxia,
Huntington’s chorea, Laurence-Moon-Biedl syndrome,
Myotonic dystrophy, Prader-Willi syndrome which were also
involved in the development of diabetes in some cases[2].
6. Diagnostic feature of diabetes mellitus
Main diagnostic criteria of diabetes are elevated blood
glucose level and the presence or absence of symptoms such
as polyurea, polydepsia and fatigueness, blurring of vision,
and weight loss, in association with glycosuria and ketonuria.
Diabetes mellitus can be confirmed by measurement of a
marked elevation of the blood glucose level. The diagnosis
of diabetes should not be based on a single plasma glucose
concentration. Diagnosis may require continued observation
with fasting or 2 hour post-prandial blood glucose levels and
an oral glucose tolerance test (OGTT). Symptoms of diabetes
plus plasma glucose concentration 曒 200 mg/dL or fasting
plasma glucose 曒 126 mg/dL and 2-hour postload glucose 曒
200 mg/dL during an OGTT were considered as diabetes[2,7].
Sometimes measurement of specific autoantibody markers
such as islet cell antibody (ICA), GAD, IA2, IAA and HbA1c
may be helpful for the diagnosis of diabetes mellitus.
Measurement of fasting insulin and C-peptide level can also
be useful in the diagnosis of type 2 diabetes in children[2].
7. Experimental models for diabetic mellitus screening
To understand the pathogenesis, complications,
and testing of various therapeutic agents appropriate
experimental models are needed. Diabetes animal
models can be obtained through spontaneously, chemical
induced or dietary or surgical manipulations. In recent
trends large numbers of new genetically modified animal
models including transgenic, generalized knock-out
and tissuespecific knockout mice have been used for the
screening of antidiabetic drugs[10]. Since the initial findings
in 1943 of alloxan induced 毬-cell necrosis in rabbits, it has
been used for inducing experimental diabetes till so far.
Alloxan is a uric acid derivative act by selectively destroying
the pancreatic beta islets leading to insulin deficiency,
hyperglycaemia and ketosis. Because of its low stability,
relatively very shorter half-life and acidic nature of solution,
intravenous route of administration of alloxan is preferred[14].
Like alloxan, streptozotocin causes hyperglycaemia mainly
by its direct cytotoxic action on the pancreatic beta cells.
In streptozotocin, nitrosourea moiety is responsible for beta
cell toxicity, while deoxyglucose moiety facilitates transport
across the cell membrane. Like alloxan, the involvement
of free radicals generation and resulting alteration of
endogenous scavengers of these reactive species have
been reported in streptozotocin induced diabetes. There
are various types of Type 2 antidiabetic screening animal
model used for the screening of drug such as spontaneous or
genetically derived diabetic animals, Diet/nutrition induced
diabetic animals, chemically induced diabetic animals,

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414
surgical diabetic animals, transgenic/knock-out diabetic
animal models[14].
8. Available therapy for diabetes mellitus
The treatment of diabetes mellitus is considered as the
main global problem and successful treatment has yet
to be discovered. Eventhough insulin therapy and oral
hypoglycemic agents are the first line of treatment for the
diabetes mellitus they have some side effects and fail to
significantly alter the course of diabetic complications[15].
8.1. Human insulin
Human insulin is a polypeptide, having a molecular
weight of about 6 000 Da, consisted of two amino acid chains
A and B, which are linked by two disulphide (-S-S-)
linkages. Normal human pancreas contains about 8-10 mg
of insulin. Insulin is not suitable for oral administration due
to inactivation by digestive enzymes. 80% of exerted insulin
is normally degraded in the liver and kidneys. The amount
of insulin secreted per day in a normal human is about 40
units. The dose of insulin required to control the diabetes
varies from patient to patient and from time to time in the
same patient[7].
8.2. Oral hypoglycemic drugs
Currently available oral therapies for treatment of diabetes
mellitus are sulfonylureas, biguanides, 毩-glucosidase
inhibitors, and glinides, which can be used alone or
combined with other drugs to achieve better effect. Many
of these oral antidiabetic agents have a number of serious
adverse effects, thus, the management of diabetes without
any side effects is still a challenge[1,8]. Sulphonylureas
are useful in the treatment of diabetes which cannot be
controlled by diet or other available therapy. Sulphonylureas
are absorbed rapidly from the intestine, some important
drugs of this group are tolbutamide, chlorpropamide,
glibenclamide, tolazamide etc. Biguanides is the other
class of oral anti-diabetic agents which control all types of
diabetes mellitus. It reduces glucose absorption from the
intestine and can also be used to treat mild diabetes during
pregnancy[7]. Natural anti-diabetic drugs from medicinal
plants, is the other available therapy for the treatment
of diabetse mellitus due to their well-known biological
activity. Substances extracted from fruiting bodies, cultured
mycelia, and culture media have exhibited promising in vitro
and in vivo biological activity including anti-diabetes[13].
There are many herbal formulation available in the market
which are used to treat diabetic mellitus such as Diabecon,
Diasulin, Pancreatic tonic 180 cp, Chakrapani, Bitter gourd
Powder, Dia-care, Diabetes-Daily Care, Gurmar powder,
Epinsulin, Diabecure, Diabeta and Syndrex[16]. If the diet of
the diabetic patients is not properly controlled, insulin or
oral hypoglycemic drugs will not act properly. A diabetic
person should take more care about his body weight and
food habit, regular exercise can also improve the utilization
of the blood glucose through different tissue in the body
which can reduces the symptoms of diabetes[7].
9. Herbal remedies for diabetes mellitus
Herbal medications have been used for the treatment of
variety of ailments, a huge number of population in the
world is entirely dependent on traditional medicines[8,17].
A number of medicinal plants and their formulations are
used for treating diabetes in Ayurvedic medicine system as
well as in ethnomedicinal practices[1]. In India, indigenous
remedies have been used in the treatment of diabetes
mellitus since the time of Charaka and Shusrutha. From the
ethnobotanical information, about 800 plants which may
possess anti-diabetic potential have been found[7,15,18].
Several plants have been used as dietary adjuvant and
in treating the number of diseases even without any
knowledge on their proper functions and constituents. This
practice may be due to its fewer side effects compare to
the synthetic hypoglycemic agents and because of their
safety, effectiveness, and availability[9,11]. Although various
synthetic drugs were developed to treat diabetes but still
very less number of drugs is available for the treatment of
diabetes[11]. There are about 200 pure compounds from plant
sources reported to show blood glucose lowering effect. The
compounds may be alkaloids, carbohydrates, glycosides,
flavonoids, steroids, terpenoids, peptides and amino acids,
lipids, phenolics, glycopeptides and iridoids. Many anti-
diabetic products of herbal origin are now available in the
market. More than 1 200 species of plants have been screened
for activity on the basis of ethnomedicinal uses[7].
The ethnobotanical information reports a huge number
of plants that may possess anti-diabetic potential, of
which Momordica charantia (M. charantia), Pterocarpus
marsupium (P. marsupium), and Trigonella foenum (T.
foenum) greacum have been reported to be beneficial for
treatment of type 2 diabetes. Herbal treatments for diabetes
have been used in patients with insulin dependent and non-
insulin dependent diabetes, diabetic retinopathy, diabetic
neuropathy etc. The families of plants with the most potent
hypoglycaemic effects include Leguminoseae, Lamiaceae,
Liliaceae, Cucurbitaceae, Asteraceae, Moraceae, Rosaceae,
Euphorbiaceae and Araliaceae[19]. Here all the enlisted
plants were pharmacologically tested in the alloxan induced
diabetic rat’s model system.
9.1. Acacia arabica
The chloroform extracts of Acacia arabica (Leguminosae)
bark in diabetic rats at 250 and 500 mg/kg, p.o. for two
weeks, significantly decreased the serum glucose level and
restored total cholestrol (TC), triglyceride (TG), high density
lipoprotein (HDL) and low density lipoprotein (LDL) level.
Moreover chloroform extract of Benincasa hispida fruit,

Patel DK et al./Asian Paicfic Journal of Tropical Biomedicine (2012)411-420 415
Tinispora cordifolia stem, Ocimum sanctum (O. sanctum)
areal parts and Jatropha curcus leaves were shown the
similar effect in the diabetic rats[20].
9.2. Achyranthes rubrofusca
The aqueous and ethanolic extracts of Achyranthes
rubrofusca (Amaranthaceae) leaves in diabetic rats were
investigated for anti-diabetic activity. It decreased the
blood glucose level significantly, pancreatic enzyme such as
superoxide dismutase (SOD), catalase (CAT) and glutathione
level were significantly increased in the treated group
compared to control group. Further aqueous extract showed
better result compared to the ethanolic extract[21].
9.3. Andrographis paniculata
The oral administration of ethanol extract of Andrographis
paniculata (Acanthaceae) in diabetic rats at a dose of 100
and 200 mg/kg, p.o. for 30 days treatment, significantly
decreased the blood glucose level. Further it restored TG,
TC, phospholipids, glycosylated haemoglobin, alanine
transaminase (ALT), aspartate transaminase (AST), acid
phosphatase (ACP) and alkaline phosphatase (ALP) level
which indicates its anti-diabetic activity[22].
9.4. Argyriea cuneata
The anti-diabetic activities of ethanol extract of leaves
of Argyriea cuneata (Convolvulaceae) in diabetic rats were
investigated and found to have significant anti-diabetic as
well as lipid lowering potential[23].
9.5. Barleria prionitis
Alcoholic extracts of leaf and root of Barleria prionitis
(Acanthaceae) in diabetic rats at 200 mg/kg, p.o. for 14
days treatment, significantly decreased blood glucose and
glycosylated hemoglobin level. Moreover serum insulin and
liver glycogen level were significantly increased[24].
9.6. Capparis decidua
The aqueous and ethanolic extract of Capparis decidua
(Capparaceae) stem in diabetic rats at 250 and 500 mg/kg,
p.o. for 21 days treatment significantly decreased the blood
glucose level which signified its anti-diabetic potential[25].
9.7. Cassia grandis
The aqueous and ethanolic extracts of Cassia grandis
(Leguminosae) in diabetic rats at the dose level of 150 mg/
kg, p.o. for ten days treatment, significantly decreased the
blood glucose, TC, and TG level proving its anti-diabetic
potential[26].
9.8. Ceriops decandra
The anti-diabetic activity of ethanolic extract of the leaves
of Ceriops decandra (Rhizophoraceae) in diabetic rats at 30,
60, 120 mg/kg, p.o. for 30 days treatment were investigated.
Extract treated group modulated all the parameters such
as blood glucose, hemoglobin, liver glycogen and some
carbohydrate metabolic enzymes. Further 120 mg/kg, p.o.
dose level was found to be more significant compared to
other tested dose level[27].
9.9. Colocasia esculenta
Ethanol extract of Colocasia esculenta (Araceae) in diabetic
rats at at 400 mg/kg, p.o. for 14 day, significantly decreased
the blood glucose level and prevented loss of body weight. It
indicates its anti-diabetic potential[28].
9.10. Costus igneus
Ethanolic extracts of leaves of Costus igneus (Costaceae)
extracts in diabetic albino rats showed significant reduction
of blood glucose level and prevented body weight loss
indicating its anti-diabetic potential[29].
9.11. Eucalyptus citriodora
Aqueous extract of Eucalyptus citriodora (Myrtaceae)
leaf in diabetic rats at 250 and 500 mg/kg, p.o. for 21 days
treatment, significantly reduced the blood glucose level
which confirms its anti-diabetic potential[30].
9.12. Ficus bengalensis
The aqueous extract of Ficus bengalensis (F. bengalensis)
(Moraceae) bark in both insulin dependent diabetes mellitus
(IDDM) and Non-insulin dependent diabetes mellitus
(NIDDM) rats at 1.25 g/kg, p.o. for 4 weeks, significantly
decreased the plasma glucose and serum lipids level. It
shows anti-diabetic potential of F. bengalensis[31].
9.13. Heinsia crinata
The ethanolic leaf extract of Heinsia crinata (Rubiaceae)
in diabetic rats for 2 weeks, significantly reduced the
fasting blood glucose levels. It indicates its anti-diabetic
potential[32].
9.14. Helicteres isora
The antihyperglycemic and hypolipidemic activities of
butanol and aqueous ethanol extracts of Helicteres isora
(Sterculiaceae) root in diabetic rats at 250 mg/kg for 10
days treatment were investigated. Extract treated group
showed decreased level of blood glucose, TC, TG and urea.
Further histological examination showed the restoration of
pancreatic islets, kidney glomeruli, and liver to its normal
size and therefore signified its anti-diabetic potential[15].

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9.15. Ipomoea reniformis
The ethanolic and aqueous extracts of stem of Ipomoea
reniformis (I. reniformis) (Convolvulus) in diabetic rats at
300 and 600 mg/kg, p.o. for 12 days treatment, significantly
decreased the blood glucose and lipid level. From the
obtained data it was found that I. reniformis have significant
anti-diabetic antihyperlipidaemic potential[33].
9.16. Juglans regia
Anti-diabetic effects of methanolic extract of Juglans
regia (J. regia) (Juglandaceae) leaves was estimated in
diabetic male wistar rats at 250 mg/kg and 500 mg/kg, p.o.
for three weeks. J. regia significantly decreased the blood
glucose, TG and TC level. Further it increased GPX, SOD and
cell antibody level significantly and therefore signified its
anti-diabetic potential[34].
9.17. Lantana aculeata
The anti-diabetic effect of ethanolic extract of the dried
mature roots of Lantana aculeata (verbenaceae) in diabetic
rats at 25, 50 and 100 mg/kg, p.o. for 30 days treatment, was
assessed. The plant significantly reduced the blood glucose
level. Further it decreased TC and TG level and increased
insulin and glycogen concentration in a dose-dependent
manner, justifying its anti-diabetic potential[35].
9.18. Limonia acidissima
Methanolic extract of Limonia acidissima (Rutaceae)
in diabetic rats at 200 and 400 mg/kg, p.o. for 21 days
treatment, significantly decreased the blood glucose and
malondialdehyde (MDA) level. Further the activity of
antioxidant enzymes such as SOD, CAT were found to be
higher in treated group compared to the control group which
show the anti-diabetic and antioxidant potential of the
plant[36].
9.19. Luffa aegyptiaca
The alcoholic and aqueous extracts of Luffa aegyptiaca
(Cucurbitaceae) in diabetic rats at 100 mg/kg, p.o. for 15
days treatment, significantly decrease the blood glucose
of hyperglycemic rats which signifies its anti-diabetic
potential[37].
9.20. Momordic charantia
Anti-hyperglycemic and anti-oxidative potential of
aqueous extracts of Momordic charantia (M. charantia)
(Cucurbitaceae) pulp in diabetic rats for 30 days treatment
were investigated. M. charantia extract significantly
decreased the blood glucose levels. Moreover all other
parameter was significantly restored in the treated group
compared to control group. Further similar activity was
found with the T. foenum graecum extract treatment[38].
9.21. Mukia maderaspatana
The methenolic root extract of Mukia maderaspatana
(Cucurbitaceae) in diabetic rats at a dose of 500 mg/kg,
p.o. for 21 days treatment, significantly decreased the
blood glucose, TC, TG, LDL, phospholipids and very-
low density lipoprotein (VLDL) level. Further it decreased
serum glutamate oxaloacetate transaminases (SGOT),
serum glutamate pyruvate transamineses (SGPT), alkaline
phosphateses (ALP) and increased total protein (TP) content
significantly at tested dose level[39].
9.22. Nymphaea pubescens
The ethanolic extract of Nymphaea pubescens (Nymphaeaceae)
in diabetic rats at 200 and 400 mg/kg, p.o. after 14 days
treatment significantly reduced the blood glucose level.
Further histopathological examination of pancreas revealed
its regenerative potential corroborating its anti-diabetic
potential[40].
9.23. Ocimum gratissimum
The methanolic extracts of Ocimum gratissimum
(Lamiaceae) in diabetic Wister rats at 500 mg/kg, p.o. showed
significant reduction of blood glucose level. Moreover
methanolic extracts of Ocimum americanum, O. sanctum
and Ocimum basilicum also showed similar effect in the
diabetic rats, with maximum potential in case of O. sanctum
compared to the other tested extracts[41].
9.24. Paspalum scrobiculatum
Aqueous and ethanolic extracts of Paspalum scrobiculatum
(Poaceae) in diabetic rats at 250 and 500 mg/kg, p.o. for 15
days treatment, significantly reduced the blood glucose
level and lipid parameters. Further extract treated group
showed a significant increase in the liver glycogen contents
and a significant decrease in glycated haemoglobin level.
Moreover 500 mg/kg, p.o. dose level showed more significant
anti-diabetic activity compared to the 250 mg/kg, p.o. dose
level[42].
9.25. Phoenix dactylifera
The Phoenix dactylifera (P. dactylifera) (Arecaceae) leaf
extract in diabetes Wistar rats at 100, 200, and 400 mg/kg,
p.o. and its fractions at 50, 100, and 200 mg/kg, p.o. for 14
days treatment, significantly reduced blood glucose, TC, TG
level and water intake but increased plasma insulin level
significantly compare to control group. The data obtained
from experiment showed that P. dactylifera have anti-
diabetic potential[43].

Patel DK et al./Asian Paicfic Journal of Tropical Biomedicine (2012)411-420 417
9.26. Phyllanthus niruri
The methanol extract of aerial parts of Phyllanthus niruri
(Euphorbiaceae) in diabetic rats significantly reduced
the blood glucose, TC and TG in a dose-related manner.
Moreover histological studies showed that extract had
imparted cell regenerative power in drug treated group
which boosted its anti-diabetic potential[44].
9.27. Phyllanthus simplex
Various fractions of Phyllanthus simplex (Euphorbiaceae)
such as petroleum ether (200 and 400 mg/kg), ethyl acetate
(100 and 200 mg/kg), methanol (125 and 250 mg/kg), water
fraction (150 and 300 mg/kg) were investigated for their
anti-diabetic potential. Methanol (125 and 250 mg/kg) and
aqueous fractions (150 and 300 mg/kg) showed significant
antihyperglycemic effect. The active fractions also restored
the antioxidant enzymes levels in liver and kidney[45].
9.28. Pongamia pinnata
The standardized ethanolic extract of Pongamia pinnata
(P. pinnata) (Fabaceae) in diabetic rats was tested for its
anti-diabetic potential. After 21-day treatment it was found
that P. pinnata Posseses significant anti-diabetic activity[46].
9.29. Solanum nigrum
Antihyperglycemic and hypolipidemic effects of aqueous
leaf extracts of Solanum nigrum (S. nigrum) (Solanaceae)
in diabetic rats at 200, 400 mg/kg b.w. for 21 days treatment
were investigated. Extracts of S. nigrum significantly
reduced the blood glucose and other lipid parameter. Similar
effect was also found with Musa extract. These findings show
the anti-diabetic potential of these two plants[47].
9.30. Sphenostylis stenocarpa
The methanolic extract of seeds of Sphenostylis stenocarpa
(Leguminosae) in diabetic rats at the doses of 200, 400 and 600
mg/kg, p.o., significantly reduced the blood glucose level.
Moreover, 600 mg/kg, p.o. was found to be more significant
compared to other tested dose level[48].
9.31. Tephrosia villosa
Ethanolic extract of leaves of Tephrosia villosa
(Fabaceae) in diabetic rats at two different doses, showed
significant reduction in the blood glucose level. Moreover
histopathological examination of pancreas showed
regenerative power and therefore signified its anti-diabetic
potential[49].
9.32. Trigonella foenum-graecum
The anti-diabetic activity of ethanol extract of Trigonella
foenum-graecum (Fabaceae) seeds in diabetic rats at 2 g/
kg, 1 g/kg, 0.5 g/kg and 0.1 g/kg, p.o. was investigated and
it was found to have significant blood glucose lowering
capacity. Further among all the tested dose level, 1 g/kg, p.o.
was found to be more significant comparing to other dose
levels[50].
9.33. Triumfetta rhomboidea
Treatment with ethanolic extract of Triumfetta rhomboidea
(T. rhomboidea) (Malvaceae) in diabetes rats at doses of 100,
200, and 400 mg/kg, p.o., significantly decreased the blood
glucose level in dose dependent manner. From the data it
was found that T. rhomboidea has significant anti-diabetic
potential[51].
9.34. Vaccinium arctostaphylos
The ethanolic extract of Vaccinium arctostaphylos (V.
arctostaphylos) (Ericaceae) fruit in diabetic male rats for
3 weeks, significantly decreased the blood glucose and
triglyceride level. However it increased the erythrocyte SOD,
glutathione peroxidase, catalase activities and expression
of GLUT-4 and INS genes. These findings indicates anti-
diabetic potential of V. arctostaphylos[17].
9.35. Vernonia amygdalina
The anti-diabetic activity of the various combinations of
metformin (50 mg/kg) and aqueous extracts of the leaves of
Vernonia amygdalina (Asteraceae) (100 mg/kg) in diabetic
rats were investigated. Extract and metformin at the ratios of
1:1 and 2:1 were given to both normoglycemic and diabetic.
From the data it was found that, blood glucose level was
decreased more significantly by the drug combination
compared to the single treatment of the drug in the diabetic
rats[52].
9.36. Zaleya decandra
Effect of ethanolic extract of Zaleya decandra (Aizoaceae)
roots in diabetes rats at 200 mg/kg, p.o. for 15 days treatment,
significantly restored the levels of glucose, TC, TG, TP,
urea, creatinine, lipid peroxidation level, and antioxidant
enzymes. Histopathological studies showed significant
regenerative power in the extract treated group compared to
the control group[8].
9.37. Zizyphus mauritiana
The petroleum ether and aqueous extract of Zizyphus
mauritiana (Rhamnaceae) at 200 and 400 mg/kg, p.o.
doses, significantly restored the elevated biochemical
parameters such as glucose, urea, creatinine, TC, TG, HDL,
LDL, hemoglobin, and glycosylated hemoglobin. From the
obtained data it was found that this plant had significant
anti-diabetic potential[53].

Patel DK et al./Asian Paicfic Journal of Tropical Biomedicine (2012)411-420
418
10. Discussion
Diabetes mellitus is a chronic metabolic disorder of
carbohydrates, proteins and fat metabolism which can be
due to absolute or relative deficiency of insulin secretion
or insulin resistance. It is characterised by high blood
glucose level, which can cause various type of secondary
complication associated with morbidity and mortality.
The number of people suffering with diabetes worldwide
is increasing at an alarming rate. It is predicated that, the
number of diabetes person could reach upto 366 million by
the year 2030[54]. Diabetes mellitus can cause both acute
and chronic complications, resulting in blindness, kidney
failure, heart disease, stroke and amputations. A proper
treatment strategy is necessary to maintain glycemic control
with proper excercise. Varieties of new pharmacologic
treatments have been developed in the past 5 years to
treat diabetes mellitus along with strategies dealing to
diet management and exercise. There are mainly two
categories of drugs available in the market for the treatment
of diabetes mellitus, i.e. insulin and oral hypoglycemic
agents[55]. Diabetic ketoacidosis is another serious metabolic
complication associated with diabetes, which includes
triad of hyperglycemia, metabolic acidosis, and increased
ketone bodies concentration in the body. Due to coexistence
of diabetic ketoacidosis and gestational diabetes mellitus
chances of fetal loss increases many fold. From the data
available in the litreature, it was found that, there is an
explosive increase in the number of people diagnosed
with diabetes mellitus worldwide in the last two decades.
Type 2 diabetes, which is associated with modern lifestyle,
abundant nutrient supply, reduced physical activity, and
obesity makes main chunk of diabetic patients. Most number
of type 2 diabetes complications are associated with obesity.
Numerous studies have shown that insulin resistance
precedes the development of hyperglycemia in subjects that
eventually develop type 2 diabetes[3]. Diabetes mellitus is the
biggest health care issue in North America and individuals
having diabetes are at high risk of heart disease and other
complications[56,57]. Oxidative stress can be an underlying
cause of many diseases, such as diabetes mellitus. It can
act through development of insulin resistance, 毬-cell
dysfunction, impaired glucose tolerance, and mitochondrial
dysfunction resulting in diabetic mellitus. Experimental
and clinical data suggest that, chronic exposure to oxidative
stress activates a series of stress pathways which can also
cause diabetes mellitus[58]. There are numbers of tests
for the diagnosis of the diabetic people, such as fasting
blood glucose measurment, oral glucose tolerance test, and
glycated hemoglobin[59-62].
Many numbers of animal models have been developed
and described for the screening of anti-diabetic drugs. But
none of them is exactly equivalent to human diabetes, but
each model acts as essential tool for investigating genetic,
endocrine, metabolic, morphologic changes and underlying
aetiopathogenic mechanisms that could be associated
with the development of diabetes[14]. Both alloxan and
streptozotocin induced diabetes model is used as screening
methods for anti-diabetic drugs. ROS in the cases of
alloxan and DNA alkylation in the cases of streptozotocin
mediate the toxic action. Due to chemical nature and greater
stability, streptozotocin is mainly used for the reproducible
induction of diabetes in experimental animals[55]. For the
screening of anti-diabetic drugs, oral glucose tolerance test,
streptozotocin or alloxan-induced diabetic animal models
are used. There are various types of mechanisms associated
with anti-diabetic activity of the compounds, which
may be related to pancreatic -cells (synthesis, release,
cell regeneration) or the increase in the protective effect
against insulinase enzyme. Other involved mechanisms
may be increase of peripheral utilization of glucose,
increase of synthesis of hepatic glycogen and decrease of
glycogenolysis, inhibition of intestinal glucose absorption,
reduction of glycaemic index of carbohydrates[19].
Medicinal plants that are effective in controlling plasma
glucose level with minimal side effects are commonly
used in developing countries as alternative therapy for
the treatment of diabetes mellitus. In Africa, hundreds of
plants are used traditionally for the management of diabetes
mellitus, but only a few of such medicinal plants have been
scientifically validated[54,63]. Currently available therapies
for diabetes such as oral hypoglycemic agents and insulin
have some side effects. A variety of chemical constituents
present in medicinal plants can act on variety of targets by
various modes and mechanisms, which can treat various
acute and some chronic complication of diabetes[64].
Though anti-diabetic plants belong to diverse groups
of families but most of them have been identified with
some specific families such as Leguminoseae, Lamiaceae,
Liliaceae, Cucurbitaceae, Asteraceae, Moraceae, Rosaceae,
Euphorbiaceae and Araliaceae, which have significant
impact on diabetes mellitus. Plant belongs in these family
such as Opuntia streptacantha, T. foenum graecum, M.
charantia, F. bengalensis, Polygala senega and Gymnema
sylvestre have been shown to possess significant anti-
diabetic potential[19]. Natural products classified into
terpenoids, alkaloids, flavonoids, phenolics, and some other
categories have shown anti-diabetic potential through
various type of modes of action. In the present review, plants
which have shown anti-diabetic activity in alloxan induced
diabetic rat have been included, among all of them M.
charantia, P. marsupium and T. foenum greacum have been
reported to have significant effect on diabetes mellitus[65].
In conclusion, this paper has presented the brief idea
about diabetes and its related complication, epidimeolgy,
diagnostic parameters, available therapies and plants
having anti-diabetic potential tested in the alloxan-
induced diabetic rat model. It showed that these plants
have hypoglycaemic effects. In some cases they showed
more significant anti-diabetic activity compared to the
standard drugs. However lots of investigations is needed
for the evaluation of mechanism of action of medicinal

Patel DK et al./Asian Paicfic Journal of Tropical Biomedicine (2012)411-420 419
plants with antidiabetic activity. Every plant material is
not safe, therefore the toxic effect of these plants should
be investigated before consumption. The less popularity
of the herbal medicine in the modern medical practices is
because of lack of scientific and clinical data, which provide
its efficacy and safety. So for the safety point of view there
is a need of conducting clinical research for herbal drugs.
Developing simple bioassays for biological standardization,
pharmacological and toxicological evaluation, and
developing various animal models for toxicity and safety
evaluation are also needed for the scientific validation of
herbal drugs. It is also important to isolate and test the
active components from the available plant extracts to
get better treatment options compared to the traditional
methods, which can be used for the treatment of various type
of disorder including diabetes mellitus.
Conflict of interest statement
We declare that we have no conflict of interest.
Acknowledgements
The financial assistance from University Grants
Commission, New Delhi, for Dinesh Kumar Patel (Senior
Research Fellowship) is greatly acknowledged.
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