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Annals of Life Sciences 4 (2019) 1–18
Research Article
Review on Antidiabetic Activity of some Medicinal Plants which are commonly used in a
Folk Herbal Compound/Medicine for Diabetes
M Khalid Iqbal1, Dr. Haseeb Anwar1,, Abdul Sami1*, Muhammad Abid1*, Imtiaz Mustafa1, Sadaqat
Ali2 Sheza Jhangir2, Aks Noor2
1. Department of Physiology, Government Collage University Faisalabad, Pakistan
1*. Department of Eastern Medicine, The Islamia University Bahawalpur, Pakistan
2. Government Collage University Faisalabad, Pakistan
*Corresponding Author’s e-mail: [email protected]
ABSTRACT
Diabetes mellitus is the most common non-communicable metabolic disorder of endocrine system. Increasing incidence of diabetes mellitus is
becoming serious problem to human health throughout the world. It is the most important cause of death in the world. There are different synthetic
compounds used to treat the diabetes mellitus were discovered directly or indirectly from plant source. Since ancient time plants have been used as
main source of medicine to treat different diseases. There are many medicinal plants have antidiabetic property. Many studies have shown that
medicinal plants with hypoglycemic activity are used to treat diabetes mellitus.
Keywords: Diabetes mellitus, Medicinal plants, Hypoglycemia, Hyperglycemia, Fat and Protein
Introduction:
Diabetes mellitus (DM) defines a group of
metabolic disorders characterized by high
blood glucose levels. People with diabetes
have high risk of developing several serious
life-threatening health complications
resulting in higher medical care costs, lower
quality of life and increased mortality [1].
Diabetes mellitus According to WHO, the
term diabetes mellitus is defined as a
metabolic disorder of multiple cause
characterized by chronic defects in insulin
secretion, insulin action, or both. The effects
of diabetes mellitus include long-term
destruction, dysfunction and failure of
various organs. Diabetes mellitus may have
the specific symptoms such as thirst,
polyuria, blurred vision and loss of weight
[5]. Diabetes mellitus is not a single disorder.
From a medical point of view, it represents a
chain of metabolic disorders associated with
hyperglycemia and caused by partial or
complete insulin insufficiency. Contact to
chronic hyperglycemia can result in micro
vascular problems in the retina, kidney or
peripheral nerves [2]. The global prevalence
of diabetes and impaired glucose tolerance in
adults has been increasing over recent years
[3-4]. A definition of diabetes from a social
perspective includes the load that the disease
places on economies, in terms of both its
expensive treatment and linked with
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premature morbidity and mortality [2]. Many
plants have been found to be beneficial in
treatment of diabetes mellitus. Plants are the
major source of drug and are available in the
bazaar as extracts directly or indirectly from
the plant sources [6]. For the purpose of
protective and curative reasons plants were
used as medicine in several parts of the
world. Medicinal herbs were used to cure
diabetes in large proportion all over the
World because of the easy accessibility and
affordability [7]. The herbal drugs with
antidiabetic activity are yet to be
commercially prepared as modern medicines,
even though they have been acclaimed for
their therapeutic characteristics in the
traditional systems of medicine [8].
Prevalence:
In 1980, the World Health Organization
(WHO) estimated that there were 108 million
people living with diabetes and this count
increased fourfold in 2014 estimates [26].
The International Diabetes Federation (IDF)
estimated the worldwide prevalence to be
151 million in 2000 [27], 194 million in 2003
[28], 246 million in 2006 [29], 285 million in
2009 [30], 366 million in 2011 [31], 382
million in 2013 [32] and 415 million in 2015
[33]. Each estimate was established on the
latest data available. It was estimated that in
2017 there are 451 million (age 18–99 years)
people with diabetes in world [34].
Types of diabetes mellitus:
Insulin Dependent Diabetes Mellitus
(IDDM, Type 1) :
Type 1 Diabetes leads to incapability to
release insulin results in low rates of glucose
acceptance into muscles and adipose tissue
[9]. Pancreatic b-cells are damaged, usually
by autoimmune inflammatory mechanisms.
Serum autoimmune markers contain islet cell
autoantibodies and autoantibodies to
glutamic acid decarboxylase (GAD); insulin,
tyrosine phosphatases IA-2 and IA-2b, and
zinc transporter ZnT8. This damaging
process typically leads to absolute insulin
deficiency with undetectable levels of plasma
C-peptide, but the rate of development can be
variable[35].
Non-Insulin Dependent Diabetes Mellitus
(Niddm Type 2) :
Type 2 diabetes usually occurs in fat
individuals and is linked with hypertension
and dyslipidemia. Thus, the treatment
purposes to reduce insulin resistance and to
motivate insulin secretion. Diabetes is a
metabolic disorder where in human body
does not yield or properly use insulin, a
hormone that is necessary to convert sugar,
starches, and other food into energy. Diabetes
mellitus is described by constant high levels
of blood glucose (sugar). Human body must
maintain the blood glucose levels at a very
narrow range which is completed with insulin
and glucagon. The function of glucagon is
triggering the liver to discharge glucose from
its cells into the blood to produce energy [9].
Gestational diabetes (Type 3):
Gestational diabetes is high blood glucose
that usually develop during the period of
pregnancy and usually disappear after giving
birth of baby. It can occur at any stage of
pregnancy but is more common in the second
half of pregnancy.
Treatment of diabetes mellitus:
Insulin and oral hypoglycemic drugs:
Insulin therapy should aim to mimic nature,
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which is remarkably successful both in
limiting postprandial hyperglycemia and
inhibiting hypoglycemia between meals.
Different products of insulin are available for
example human insulin, beef insulin, pork
insulin. Insulin therapy is not free from
problems and adverse effects. The most
significant adverse effect are weight gain and
hypoglycemia when inappropriate dose of
insulin is taken and when there is mismatch
between meals and insulin injection. They
bind to sulfonylurea receptors on the ß-cell
plasma membrane, triggering closure to ATP
sensitive potassium channels, leads to
depolarize the cell membrane.
Administration of sulfonylureas to type 2
DM patient’s rises insulin release from the
pancreas and may be further increase insulin
levels by reduce hepatic clearance of the
hormones. It has been shown to increase
peripheral acceptance of glucose, and to
decrease hepatic glucose output almost 20-
30% when given orally but not intravenously.
Impaired absorption of glucose from the gut
has also been recommended as a mechanism
of action [10].
Herbal treatment of diabetes:
WHO are listed 21,000 plants, which are used
for curative purposes throughout world.
Among these 2500 species are in India, out of
which 150 species are used commercially on
a properly large scale. India is the biggest
producer of medicinal herbs and is called the
botanical garden of the world [10]. Among
these listed medicinal plants, many plants are
used to cure diabetes throughout the world.
Active anti-diabetic ingredients
extraction techniques:
Most of the extractions used in plants extract
research are linked with the conventional
techniques. In conventional extraction, the
release of the preferred compounds
traditionally required soaking and maceration
in mild solvents. In traditional Chinese
medicine practices, decoction in water is
mostly employed and is an effective method
to be considered in cases where the existence
of a chemical solvent is undesired [11-12]. In
addition to the soaking/maceration technique,
percolations using methanol and ethanol on
the stem were also useful [13-14]. Other
solvents for example acetone, petroleum
ether and hexane have also been used as
solvents in the conventional extraction [15-
16]. Additionally, extraction by liquid
nitrogen was also observed in some research
works [17]. The Soxhlet technique for
extracting anti-diabetic ingredient was not
famous until 2005, after which the extraction
technique was incorporated with ethanol and
light petroleum [18-19]. Other than solvent
extraction techniques such as lyophilization
[20-21] and sonification [22-23] have also
been used. Furthermore, supercritical fluid
extraction and microwave assisted
techniques have also been used in recent
decades. Supercritical fluid extraction on
lotus gem were carried out by Taiwanese
research teams to investigate the antioxidant
activity of the extract [24] and microwave-
assisted extraction was used to investigate the
bioactivity of tea flower polysaccharides
[25]. These two advanced, non-conventional
techniques offer attractive benefits of short
extraction time and solvent free active
compounds, respectively. The techniques
used in the extraction are tabulated in Table
1. The extraction techniques generally used
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in plant research are lacking in the
involvement of the engineering aspect as
well, and hence the processes are not
optimized. As a result, the therapeutic
effectiveness of the plants under
investigation might be affected.
Table 1: Various techniques used in plant extraction
Conventional extraction Non-conventional extraction
Water Soaking
Maceration by water, ethanol,
methanol
Solvent extraction (ethanol,
methanol, petroleum ether,
hexane, acetone, etc.)
Percolation by water
Soxhlet extraction involved
solvents
Lyophilization
Sonification
Supercritical fluid extraction
(carbon dioxide)
Microwave assisted Extraction
Antidiabetic effect of medicinal plants:
Momordica charantia (Cucurbitaceae):
Scientific name: Momordica charantia,
Kingdom: Plantae, Division: Magnoliophyta,
Family: Cucurbitaceae, Genus: Momordica,
Species: Charantia, Duration: Annual [37].
Some common names of M.charantia
include bitter melon, ampalaya, papilla, bitter
gourd, kho gua, salsamino, corrila or karela,
hanzal, assorossie, nigauri or goya, sora,
balsam apple, pear, pear or balsa mina, and
numerous other common names (see Taylor,
2002 [36] for extensive review and technical
data). M. Charantia is a flowering vine. It is
a tropical plant that is broadly cultivated in
Asia, India, East Africa, and South America
for its intensely bitter fruits that are
commonly used in cooking and as a natural
medication for treating diabetes [44]. It is a
climbing perennial that commonly grows up
to 5m and contain elongated fruits with a
knobby surface. It is a useful medicinal and
vegetable plant for human healthiness and
one of the most gifted plants for diabetes
[45]. Various animal studies have frequently
shown hypoglycaemic effects of the seeds,
leaves, fruit pulp and whole plant of MC in
normal animals [42-43]. Numerous
phytochemicals containing hypoglycemic
properties have been isolated from M.
charantia fruit. These phytochemicals
include glycosides (momordin, charantin),
alkaloids (momordicin), and polypeptide p
[39]. Ingredients of Momordica charantia
such as momocharin and momordicin which
is believed to have insulin-like chemical
structure and properties [37]. Charantin,
vicine and p-insulin (polypeptide) are also
reported as the active ingredients. It is a
famous herbal resource to treat diabetes. It
rises the mitosis of pancreatic cells and
partially recovers the ruined cells [38]. M.
charantia decrease plasma and hepatic
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triglyceride content and tissue fat
accumulation [40-41]. Various medicinal
properties are claimed for Momordica
charantia namely anti diabetic, anthelmintic,
abortifacient, antimalarial and laxative and in
galactogogue, jaundice, contraceptive,
pneumonia, leprosy and rheumatism [38].
Cinamomum zeylanicum (Laurceae) :
Cinamomum zeylanicum commonly known
as Dalchini, Darchini, Family: Laurceae.
Commonly part used is Bark. Main
mechanism of action is elevation in plasma
insulin that decrease the glucose level [48].
Cinnamon is a native of tropical Asia and Sri
Lanka. The tree occurs in South India up to
heights of 500 m but is common at lower
heights. The tree occurs in month of January
and fruits ripen from month of May to
August. Cinnamon has been used as a spice
for thousands of years in different recipes. In
Ayurvedic medicine, cinnamon bark has
been used as an antiemetic, antiflatulent,
antidiarrheal and general stimulant [46-47].
Interest in cinnamon as a theoretically useful
treatment for type 2 diabetes began almost 20
years ago. There was isolate an unidentified
factor from cinnamon and named it as insulin
potentiating factor (IPF). They demonstrated
that IPF may be involved in the lessening of
the signs and symptoms of diabetes, and
other diseases related to insulin resistance
[49]. Active chemical constituents are
volatile oil, mannitol, tannin, ca+.oxalate
[48].
Citrullus colocynthis (Cucurbitaceae) :
Citrullus colocynthis also known as bitter
apple, is a desert plant of the family
Cucurbitaceae naturally modified to
dehydrate environments. It is a non-hardy,
herbaceous perennial vine, branched from the
base. Originally from tropical Asia and
Africa, it is now broadly distributed in the
Saharo-Arabian phyto geographic region in
Africa and the Mediterranean region [53].
Each plant yields 15-30 round fruits, about 3-
4 inches in diameter, green with undulate
yellow stripes and becoming yellow all over
when fruits dry. Seeds are small (1-4 inch or
less in length) smooth and brownish when
seeds ripe. The fruits are widely used
medically, especially for stomach pains the
pulp, due to its content of glycosides such as
colocynthin, it is an effective cathartic and
laxative. Several plant secondary metabolites
including cucurbitacins, flavonoids, caffeic
acid derivatives and terpenoids have earlier
been reported from this plant [54-55-56].
Citrullus colocynthis (CCT) is traditionally
used as an antidiabetic treatment in tropical
and subtropical countries [50]. This plant can
induce insulinotropic [51] and mild
immunostimulating effects [52]. The present
study was planned to test the acute and sub-
acute antihyperglycemic effect petroleum
ether extract of Citrullus colocynthis fruits on
Streptozotocin induced Diabetic rats. Oral
administration of two changed doses
(300&500 mg/kg P.O) of Citrullus
colocynthis fruit extract showed a significant
reduction in blood glucose level in diabetic
rats. [57].
Eugenia jambolana (Myrtaceae) :
Eugenia jambolana (EJ) usually known as
Jamun which belongs to the family
Myrtaceae, is a large evergreen tree growing
up to 30 m height, found widely in India and
the Asian subcontinent. The seeds of this
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plant have been reported to have many
medicinal properties in the Ayurveda system
of medicine. The fresh seeds are most
effective in diabetes as they quickly lessen
sugar in urine [58-59-60]. This study was
undertaken to study the effects of changed
doses (100, 200 and 400 mg per day) of
alcoholic and aqueous extracts of EJ on the
metabolic parameters (body weight and
serum glucose, insulin and triglycerides
levels) of fructose fed rats. Fructose feeding
for 15 days increased serum glucose and
insulin levels significantly and triglycerides
levels slightly vs. control (75.46 2.41 vs.
55.59 2.89 mg /dl, 6.26 1.27 vs. 15.04 2.43
mg /dl and 50.93 3.30 vs.41.1 3.33 mg /dl,
respectively). Treatment with 400mg per day
of aqueous extracts of EJ for 15 days
substantially prevented hyperglycemia and
hyperinsulinemia induced by a diet high in
fructose [61].
Gymnema sylvestre (Asclepiadaceae) :
Gymnema sylvestre (Family:
Asclepiadaceae) is a large, woody and
branched climber, distributed in the tropical
and sub-tropical areas of the world. It is
widely used in traditional systems of
medicine and mentioned in the traditional
literatures of Japan, Australia and Vietnam.
In India, it has been used in Ayurveda, the
traditional health care system, for several
centuries [62–63]. Many chemical
constituents are separated and characterized
from the plant. Gymnemic acids are
described to be the main class of chemical
constituents of Gymnema sylvestre.
Gymnemic acids I–IV were the constituents
considered to be of major importance, first
reported from the leaves of the plant followed
by gymnemic acids V and VI [66–67]. All
these constituents were isolated and
characterized from the aqueous extract of
leaves. Further investigations shown the
presence of gymnemic acids VIII and IX in
addition to gymnemic acids X–XII, which
were explained as glucosideuronic acid
derivatives of gymnemagenin acylated with
acetyl, tigloyl and/or 2-methylbutyroyl
moieties [67–68] Gymnemic acids III, IV, V,
VII and gymnemosides b were recognized as
the anti-hyperglycemic active constituents
[69]. Gymnema sylvestre is primarily used in
the treatment of diabetes and related
disorders. Separated compounds from the
leaves on oral and parenteral administration
were found to be useful in the treatment of
diabetes, impaired glucose tolerance, and
various situations associated with diabetes.
Moreover, these compounds decrease
polyuria, polydipsia and polyphagia,
regenerate the pancreatic cells, increase
endogenous insulin, lipase and amylase
levels, increase production of proinsulin and
c-peptide, and lesser blood lipids and
triglycerides and free fatty acids. A hydro
alcoholic extract without water-soluble
fraction significantly lower fasting blood
glucose levels, elevate pancreatic amylase
and lipase levels and number of pancreatic
islets and beta cells [64]. Separated
compounds in the form of pharmaceutically
acceptable salts can also be used in the
prevention or treatment of ailments related to
high blood sugar, high blood lipids, or blood
clotting [65].
Holarrhenaantidysenterica
(Apocyanaceae) :
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Holarrhena antidysenterica, Family:
Apocyanaceae, commonly known as Kurchi
[73]. Flowering and Fruiting Time from
February to June. Holarrhena
antidysenterica bark is collected from 8-10
years old plant. The bark of Kurchi is free
from attached wood and is peeled into small
parts. Kurchi is native to India and is found at
higher altitudes of 1000 meters. It is found in
Himalayan region and in the Assam, Uttar
Pradesh, states of Orissa and Maharashtra
[71]. About 30 alkaloids have been separated
from the plant, commonly from the bark.
These include conessine, kurchine, conimine,
kurchicine, conarrhimine, conessimine, iso-
conessimine, conaine, holacetin,
holarrhimine, and conkurchin [72]. The
ethanolic extract of H.antidysenterica seed
has antihyperglycemic activity as it drops
serum glucose level in diabetic albino rats
and significantly increases glucose tolerance.
It stops weight loss in diabetic rats and
corrects changed biochemical para meters
e.g. serum cholesterol, urea, triglyceride,
alanine transaminase, alkaline transferase,
total protein, aspartate transaminase,
creatinine and uric acid to near normal
physiological range. This is a signal of its
better metabolic control and powerful
antidiabetic property. Hence, further studies
are necessary to know the exact mechanism
of action and constituent responsible for
antidiabetic effect [70].
Nigella sativa (Ranunculaceae) :
Nigella sativa Linn. (family Ranunculaceae),
commonly known as black seed or black
cumin, is an annual plant that has been
frequently used in the Indian subcontinent
[75], Arabian countries [76] and Europe [77]
for cooking and medicinal purposes as a
natural medicine for a number of illnesses
and conditions that include asthma, diabetes,
bronchitis, inflammation, cough, headache,
eczema, fever, hypertension, dizziness and
influenza [78]. N. sativa seeds contain 36%–
38% fixed oils, alkaloids, proteins and
saponin and 0.4%–2.5% essential oil [74].
The effect of N. sativa on certain of the
complications of experimental (alloxan-
induced) diabetes mellitus in rabbits has been
investigated by several workers [79-80-81].
It was described that intraperitoneal
administration of the volatile oil of N. sativa
seeds (50 mg/kg) significantly reduced (by
about 15%–23%) the fasting blood glucose
concentration in normal and hyperglycemic
rabbits, 4–6 h after administration. Insulin
concentration was not affected by the
treatments, possibly indicating that the
hypoglycaemic effect was facilitated by an
(yet unidentified) mechanism that does not
involve insulin [79].
Swertia chirata (Gentianaceae) :
Swertia chirayata commonly known as
Chirayata, Family: Gentianaceae, Whole
plant is used. Main mechanism of action is to
stimulate insulin release from islets [82]. A
methanol extract of S. chirata plant (CT)
possessed antidiabetic activity and contains
mangiferin (MG), amaroswerin (AM),
sweroside (SW), amarogentin (AG) and
swertiamarin (SM) as major active
constituents [88]. These active constituents
are known to have antidiabetic, antitumor,
antiviral, chemo preventive, anticholinergic,
antioxidant and immunomodulatory activity
[83-84-85-86]. The hexane fraction of the
alcoholic extract of S.chirayita is reported to
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indicate significant hypoglycaemic activity
in albino rats [88]. Single oral administration
at a dose of 250 mg/kg body weight induced
at once a drop-in blood sugar and an increase
in plasma immune reactive insulin (IRI)
without inducing liver glycogen
concentration. Interestingly, daily
administration of the crude fraction at the
same dose for 28 days resulted in a significant
rise in liver glycogen level. It is suggested
that the hexane fraction may not be capable
of inhibiting intestinal absorption of glucose
and probably acts through its insulin-
releasing effect [89].
Terminalia chebula (Combretaceae) :
Terminalia chebula (T. chebula) is a
flowering evergreen tree of the family
Combretaceae. It has numerous common
names such as black myrobalan, ink tree, or
chebulic myrobalan (English), haritaki
(Sanskrit and Bengali), harada (Marathi and
Gujrati), harad (Hindi), Karkchettu (Telgu)
and Kadukkaya (Tamil). In Tibet, T. chebula
is known as the “King of Medicine” [90]. T.
chebula has been reported to exhibit a range
of biological activity, including antidiabetic
[96], anticancer [95], antimutagenic [97-98],
antibacterial [99], antifungal [100], and
antiviral [101-102] activities, etc. Oral
administration of 75% methanolic extract of
T. chebula (100mg/kg body weight) decrease
the blood sugar level in normal and alloxan
diabetic rats significantly within 4 h.
Continued daily administration of the drug
created a sustained effect [91]. The
chloroform extract of T. chebula seeds (100,
200 and 300 mg/kg body weight) created
dose-dependent reduction in blood glucose of
diabetic rats in both short term and long-term
study (300mg/kg body weight for 8 weeks).
Further, notable renoprotective activity was
also observed in T. chebula treated rats [92].
Oral administration of ethanolic extract of
fruits of T. chebula (200 mg/kg body weight
for 30 days) reduced the levels of blood
glucose and glycosylated hemoglobin in
streptozotocin (STZ)-induced investigational
diabetic rats [93]. In a similar study, aqueous
extract of T. chebula (200 mg/kg body weight
for two months) decrease the raised blood
glucose and increase in glycosylated
hemoglobin [94].
Tinospora cordifolia (Menispermaceae) :
Tinospora cordifolia (Willd.) Miers ex Hook.
F. & Thoms is a large, glabrous, deciduous
climbing shrub belonging to the family
Menispermaceae [103-104]. The stems of
Tinospora cordifolia are juicy with long
filiform fleshy aerial roots from the branches.
It is extensively used in folk and ayurvedic
system of medicine as general tonic,
hepatoprotective, antiperiodic, anti-
spasmodic, anti-inflammatory, antiarthritic,
anti-allergic and antidiabetic [104-105-106-
107-108-109-110-111]. A variety of
constituents are present in TC plant
belonging to different classes such as
alkaloids, diterpenoid lactones,
sesquiterpenoid, glycosides, steroids,
aliphatic compounds, phenolics and
polysaccharides. Water soluble isoquinoline
alkaloids viz., jatrorrhizine, palmatine,
berberine, tembetarine, magnoflorine,
choline, tinosporine, isocolumbine and
hydrastine are also existing (112-113-114-
115-116-117-118-119]. The oral
administration of several extracts (hexane,
ethyl acetate and methanol) of T. cordifolia
stem was found to have powerful antidiabetic
property by reducing blood sugar level in
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streptozotocin induced diabetic rats at a dose
of 250 mg/ kg [120]. Saponarin separated
from leaf extract of T. cordifolia presented
hypoglycemic activity at doses of 20-80
mg/kg [121]. The hydro alcoholic and
chloroform extracts of T. cordifolia stem
reveals significant antidiabetic property at
250 and 500mg/kg dose dependently in
alloxan induced diabetic rats [122-123].
Conclusion:
Diabetes mellitus is a metabolic disorder
characterized by defects in insulin action and
secretion. According to the World Health
Organization diabetes mellitus increasing
day by day throughout the world. Many
synthetic drugs that are available in markets,
used to treat diabetes mellitus but have many
side effects. Many antidiabetic plants
traditionally used in the treatment of diabetes
mellitus. These medicinal plants have less
toxic effect and have no side effect. There
are many bioactive chemicals that are
responsible for antidiabetic property of these
antidiabetic plants. Further investigations
should be carried out to find the mechanism
of action of these antidiabetic plants.
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