Traditional medicinal plants of Manipur as
L. Warjeet Singh
Department of Chemistry, Manipur University, Canchipur-795003,
Accepted 19 October, 2010
Manipur, which lies in the North-eastern part of India, is rich
in its flora and fauna; and is one of the hotspots of
biodiversity. The flora of this region includes aromatic and
medicinal plants with a number of bioactive compounds. Before
the coming of the modern pharmacological medicines, the people
of Manipur use medicinal plants for the treatment of diabetes
mellitus. Even today, people not only in the rural areas but
those living in the urban areas are also using these traditional
medicines, and give first preference to herbal treatments by
consulting the medicine men. An outline of the medicinal plants
of Manipur which are used for curing diabetes is reported.
Traditional, plants, Manipur, anti-diabetics.
Since ancient times, plants have been used as herbal medicines.
Ayurveda has a 5000 years old rich heritage of role of the use of
plants in the treatment of various human ailments as alternative
medicines. The ethno-botanical information reports about 800 plants
that may possess anti-diabetic potential. A wide array of plant
derived active principles representing numerous chemical compounds
has demonstrated activity consistent with their possible use in the
treatment of diabetes mellitus (DM). DM can be defined as a group of
syndromes characterized by hyperglycemia altered metabolism of
lipids, carbohydrates and proteins along with an increased risk of
complications from vascular disease. In simple terms, diabetes can
be defined as a chronic disorder of metabolism caused by a relative
or absolute lack of insulin in the body. Its primary characteristic
is a high level of sugar in the body, in the fasting and/or post
meal stages. During the normal digestion process, the body turns the
food consumed into glucose and the insulin hormone helps the glucose
so generated to reach the body cells. However, in diabetics, due to
inadequate insulin - and its inadequate action, as a result - the
glucose stays in the blood. Though several hormones are involved in
the maintenance of diabetes, the most important ones are insulin and
Diabetes is caused as a result of the loss of the balanced effect
of these hormones, usually due to less insulin production, sugar
starts accumulating in the blood and blood-sugar level increases and
sugar passes in urine along with other minerals. High blood-sugar
level is known as “hyperglycemia” and the presence of sugar in the
urine is known as “glycosuria”. Insulin is secreted by β-cells of
islets of Langerhans of pancreas and is necessary for the burning of
sugar in the tissues with the help of oxygen. Thus, DM is a group of
syndromes characterized polydipsia (drinking large amount of water),
polyuria (excretion of large amount of dilute urine) and glycosuria
(excretion of glucose in urine).
Knowledge about DM existed in ancient Egypt and Greece. 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). Earliest reference
about a disease with ‘polyurea’ was made in “Ebers Papyrus” (Egypt),
a document outlining clinical symptoms of the disease (1550 BC).
Greeks had a knowledge of a disease (Celsus, 30-38 AD) accompanied
by polyurea and wasting of body, whereas Aretaeus of Cappadocia (150
AD) mentioned a disease characterized by thirst and polyurea which
was christened as Diabetes. Subsequently, the knowledge permeated to
Chinese (Tehang Tehong King, 200 AD), Iranians (Rhazes (860-932 AD)
and Arabians (Avicena, 980-1037 AD).
From the Middle East, the knowledge of DM had spread into Spain (Mermonides,
1135-1204 AD) as a disease characterized by polyurea, polydipsia
with sugary flavoured urine. With discovery of sugar in urine
(Thomas Wills, 1664 AD) and its detection by laboratory test (Mathew
Dobson, 1776 AD), the knowledge permeated into 18th century. Today,
around 30 million people throughout the world suffer from DM. It is
the most common metabolic abnormality in the world. Non-insulin
dependent diabetes mellitus (NIDDM) is the most common form of
diabetes constituting nearly 90% of the diabetic population in any
country. Its prevalence varies in different geographic regions and
also in different ethnic groups.
National Status of DM
The term Diabetes mellitus was recognized as ‘Madhumeha’, a type of
‘Prameha’, in primeval times. The knowledge of the system of DM
existed with the Indians since prehistoric age. Its earliest
reference (1000 BC in the Ayurbedic literature) was found in
mythological form where it is said to have originated by eating
Havisha, a special food which used to be offered at the times of
Yagna organized by Daksha Prajapati. The disease was known as
‘Asrava’ during vedic era (600 BC) and a detailed description of it
is available in Brahatta, viz. Charak Samhita, Sushruta Samhita and
Vagbhatta. Asthanga Haridaya (600 AD) is the first medical treatise
in which one gets clear definition of ‘Madhumeha’ by mentioning
glycosuria (madhviv mehati - honey like urine). The word, ‘Prameha’
is derived from the root ‘miha sechane’ meaning watering. In
reference to disease of human beings, it may have a meaning of
passing urine, qualified by prefix ‘pra’ meaning excess in both
frequency and quantity. Thus, ‘Prameha’ means ‘Pra’ (excessive)-‘Meha’
According to ancient Hindu physicians, ‘Madhumeha’ is a disease in
which a patient passes sweet urine and exhibits sweetness all over
the body, that is, in sweat, mucus, breath, blood, etc. They knew of
the fact that the urine of a Madhumeha patient tastes sweet. They
had recorded in their observations that - ‘if too many ants swarm
around a spot of urine, one can state that Prameha of any variety,
if neglected, will finally lead to Madhumeha and in due course
become incurable’. It is interesting to note that although symptoms
of the disease were known to ancient Hindu physicians, clear cut
knowledge about the treatment of the disease was not handy although
suitable dietary therapy, that is, use of oils (unsaturated fat)
instead of animal fat (saturated fat), was recommended. It is
evidenced by the fact that as early as Charak-Susruta era (600
BC), it was recommended that addition and restriction of certain
foods were an adjunct to treatment of Madhumeha (Grover and Vats,
2001). It was recommended that the low carbohydrate diet (low sugar
- low starch) and almost total withdrawal of animal fats should be
taken recourse to by patients suffering from Madhumeha. However, it
was also felt that lean and young patients should be prescribed
nourishing diet, whereas obese adults should live on low calorie
diet. Use of vegetable oil was generally recommended. The severity
was high in urban areas and many cases go unreported due to lack of
education on the disease as it is not contagious like malaria or
tuberculosis. According to the India Council of Medical Research (ICMR),
it had reported a prevalence of 2.3% in the urban and 1.5% in the
rural areas. According to a report came from the multicentre study
conducted by the ICMR, the estimated burden of Diabetes in India was
22 millions in 1990, 28 million in 1995 and 33 millions in 2000. It
is a very large and continuously growing health problem and adequate
treatment is often not available.
Types of Diabetes Mellitus
There are two types of Diabetes mellitus – Type 1, “Juvenile
Diabetes mellitus” (Insulin Dependent Diabetes Mellitus, IDDM),
which is hereditary and is treated by giving insulin; and Type 2,
“Adult type” (Non-Insulin Dependent Diabetes Mellitus, NIDDM), which
occurs in elderly people and is treated by controlling the diet and
oral anti-diabetic drugs should be given. The main symptoms of these
types of diabetes are, increased thirst, increased urinary output
and ketonaemia and ketouria, that is, presence of ketone bodies in
the blood and urine. Diabetes should be suspected when any of the
symptoms are present. If there is any history of diabetes in one’s
family, then an individual should check for diabetes.
In the insulin dependent diabetes mellitus (IDDM), people do not
produce insulin and have to take it every day to filter out the
glucose from their blood and into their cells as fuel. Here,
sometimes there is damage to the pancreas, the organ that produces
insulin. IDDM is not associated with obesity and is complicated by
ketosis (that is, piling of ketone bodies in the blood stream) and
acidosis. In type II diabetes (NIDDM), the amount of insulin that is
produced is not enough or the cells of the body do not respond to
its presence. NIDDM is usually associated with normal β-cell
morphology and insulin content, if the β-cells have not become
exhausted. Obviously, the former kind is more severe and the later
is more common especially in developing countries such as India.
Thus, in IDDM, a high blood sugar level due to failure of the
β-cells in the pancreas is found whereas in NIDDM, a high blood
sugar level due to failure of cells to take up glucose is found.
The exact causes of pancreatic failure and loss of cellular
acceptance of insulin are unknown, but are associated with disease,
environmental, and/or dietary conditions.
Human insulin, which is secreted by beta cells of the islets of
langerhans of pancreas, is a polypeptide, having a molecular weight
of about 6,000. It consists of two amino acid chains A and B, which
are linked by two disulphide ( –S–S–) linkages between cys (cystidine)
7 of A with cys 7 of B, cys 20 of A and cys 19 of B, and an intra
-S-S- linkage between cys 6 and cys 11. The chain A contains 21
amino acids and chain B contains 30 amino acids, all in a known
sequence; hence it is a polypeptide chain having 51 amino acids. The
disulphide bridges are essential for its biological activity. Normal
human pancreas contains about 8-10 mg of insulin. Insulin is an
amphoteric protein and forms salts with weak acids and alkalis. It
is soluble in water. It can combine with proteins such as protamine
and with zinc without any change in its biological activity.
It is inactivated by digestive enzymes; hence it is not suitable for
oral administration. The free amino and aliphatic hydroxyl groups of
insulin are not required for biological potency. The solubility of
insulin depends on its physical state (that is, amorphous or
crystalline), on the concentration of zinc and on the nature of
buffer in which it is being suspended. All tissues have the ability
to metabolize insulin, but 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 (286 mmol). In normal
individuals, insulin secretion is low between meals and increase
with each meal. Duplication of pattern of secretion can be achieved
in diabetes with portable electronic insulin pumps programmed to
inject. Following intravenous insulin administration, the decline is
maximal in about 30 min; following the subcutaneous administration,
it is maximal in 2-3 h. The dose of insulin required to control the
diabetes varies from patient to patient and from time to time in the
Diagnostic tests for Diabetes in urine and blood
Diabetes can be detected by the glucose tolerance test (GTT), which
divides diabetes according to the sugar level of the patient as
normal, mild, moderately severe, or severe diabetes. Diagnostic
tests for diabetes in urine and blood are discussed here. There are
two tests which are commonly used to show the presence of sugar in
urine - (a) Benedict’s test, and (b) Fehling’s test. Among these two
tests, Benedict’s test is more satisfactory and is used more
frequently. For Benedict’s test: take 5 mL of Benedict’s reagent
in a test tube and add 5 mL of urine and mix. Heat the test tube
for 5 min. in water bath and cool spontaneously. A greenish to
yellowish brown to reddish brown precipitate is formed which shows
the presence of sugar. A white precipitate may be produced due to
the presence of phosphate, but this is not recorded. If the solution
appears green due to the suspension of a yellow precipitate, then
the presence of reducing substance or sugar is indicated as “trace”.
If the solution shows a yellow tinge, result is reported as ‘+’, an
orange precipitate as ‘++’ and a brick red precipitate as ‘+++’.
Blood glucose analysis is of great value in detection of diabetes.
Due to hormonal control, blood sugar level is maintained constant at
a value of 70-120 mg of glucose per 100 mL. Though several hormones
are involved in this, the most important ones being insulin and
glucagon. By diet control, the presence of sugar in the urine may
come down to normal range. But this may not be so in the blood where
the sugar level may be beyond the normal range. Thus, the severity
of the diabetic condition, that is, when the blood sugar level is
160-180 mg/dL, can be known only by blood-sugar tests. One of the
important blood sugar tests for detecting the diabetic condition is
the sugar tolerance test or glucose tolerance test (GTT). This test
is usually carried out in the morning after a night’s fast but, if
necessary, it may be done some four or five hours after the last
food was taken. Blood samples are taken for the determination of
fasting blood sugar. After withdrawing the blood sample, the patient
is orally given 1.75 g of glucose/kg body weight and blood samples
are taken subsequently at half, one and two hours intervals and the
blood sugar level is determined. In the normal case, the blood sugar
level rises to about 150 after an hour, then starts falling and at
the end of two hours, the normal level is restored. In diabetic
condition, the sugar level rises higher at 200-300 mg and stays high
for a longer time, i.e., 3-6 h. Further, the peak value is reached
in longer time (2 h). In non-diabetics, the peak of the curve is
usually between half and one hour. For estimation of sugar, sodium
fluoride (100 mg/mL) has to be added to the blood immediately after
collection. This is done to inhibit blood enzymes which alter the
amount of glucose in blood during storage. Within limits, however,
the glucose concentration of blood in the body responds to a variety
of biochemical and physiological events. Such factors as stress,
size and sugar content of meals, rate of digestion, and agents that
alter glucose absorption and metabolism allow sugar levels to be
modified at several points throughout the glucose cycle in the body.
If diabetes is properly controlled, a diabetic patient can live a
normal long life. Diabetes can be controlled by stabilizing the body
metabolism. Control of diabetes should be continued for years.
The diet control is of immense importance in controlling
diabetes and should be maintained life long. If the diet of the
diabetes is not properly controlled, insulin or oral hypoglycemic
drugs will not control the disease properly. A diabetic person
should control his or her body weight and should avoid overeating.
Regular exercise should be included in daily routine as the muscles
live on glucose and exercise helps them to utilize it. Diabetic
patients are more vulnerable to infectious skin diseases like boil,
carbuncles, etc. These infections must be attended immediately and
proper care should be taken.
sulphonylureas and biguanides
The drugs which lower the blood sugar and can treat the symptoms of
DM are known as hypoglycemic drugs. These drugs could be categorized
as (i) insulin and insulin preparation, which are employed only
parenterally, and (ii) oral hypoglycemic drug which can be
administered orally. As insulin are ineffective through oral
administration, oral hypoglycemic drugs are introduced which could
control diabetes when administered orally. Although the drugs
available now do not meet all the requirements, but the most
important drugs belong to two groups, namely, sulphonylureas and
biguanides (Figure 1). Sulphonylureas are useful in treating
diabetes which can not be controlled by diet alone. These drugs can
be used to treat mild diabetics during pregnancy. Sulphonylureas are
quickly absorbed from the intestinal track. These drugs are
ineffective in Juvenline diabetes, and in presence of ketosis and
during severe stress. Some important drugs of this group are
tolbutamide, chlorpropamide, glybenclamide, tolazamide, etc.
Biguanides control all types of DM. These drugs reduce glucose
absorption from the intestine. These drugs can be used to treat mild
diabetes during pregnancy. Though these drugs are not used in
treating Type I, but it is used along with insulin to control Type
I. These drugs which have been used as oral hypoglycemic agents do
not affect insulin secretion but lowers the blood sugar in diabetics
by directly increased the uptake of glucose by cells and by actively
promoting its glycolysis via the Embden Mayerhof (pathway to
pyruvate and lactate). Some important drugs of this group are
phenformin and metformin, which can be obtained from Zingiber
show Hypoglycemic activity (Herbal Anti-diabetes)
Since ancient times, traditional medicines all over the world have
advocated the use of plants to treat diabetes. The ethno-botanical
information reports about 800 plants that may possess anti-diabetic
potential (Alarcon et al., 1998). Main symptoms targeted were thrist,
polyuria and glycosuria. Most of the drugs from plant sources are
secondary metabolites which have no role in plant metabolisms but
are postulated to play a significant role in the plant defense
mechanism. A wide array of plant derived active principles
representing numerous chemical compounds has demonstrated activity
consistent with their possible use in the treatment of NIDDM (Bailey
and Day, 1989; Marles and Farnsworth, 1995). 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. Inolter is one of them; each capsule of Inolter contains
Momordica charantia (fruits, seeds and leaves, 100 mg), Trigonella
foenum graeceum (seeds, pods and leaves, 100 mg), Asphalt (100 mg),
Gymnema sylvestre (Root and leaves, 100 mg) and Eugenia jambolena
(seeds, fruits and bark). Inoltar is claimed to have properties of
releasing of insulin from islet of langerhans and as an insulin
sensitizer (Shanmugasunderam et al., 1990). A scientific clinical
trial has been conducted to study the role of Inoltar (herbal
product) in the management of type 2 diabetes (Kothari et al.,
2002). Several herbs have shown anti- diabetic activity when
assessed using presently available experimental techniques (Saifi et
al., 1999). Although, oral
hypoglycemic agents/insulin are the mainstay of treatment of
diabetes and are effective in controlling hyperglycemia, they have
prominent side effects and fail to significantly alter the course of
diabetic complications (Rang and Dale, 1991).
More than 1200 species of plants have been screened for activity on
the basis of ethnopharmacology or on random basis. The products
obtained range from marine algae and fungi to phytogenetically
advanced classes of compounds. Plants that demonstrate hypoglycemic
activities within the body play a major role in folk medicine, and
various studies on folklore have identified approximately 50 plants
that affect the sugar level in blood.
Manipur, which lies in the North-eastern part of India, is rich of
its flora and fauna; and is one of the hotspots of biodiversity. The
flora of this region includes aromatic and medicinal plants with a
number of bioactive compounds. Most of these medicinal plants are
required to identify the active principles present in these plants.
Before the coming of the modern pharmacological medicines, the
people of Manipur is using medicinal plants for the treatment of DM.
Even today, people not only in the rural areas but those living in
the urban areas are also using these medicines, and give first
preference to herbal treatments by consulting the medicine men. A
report of some commonly used anti-diabetic plants which are found in
Manipur, North-East India in the indigenous system of health care is
Acacia arabica or nilotica
Feeding of 94% seed diet to normal rats showed significant
hypoglycemic effect versus controls. However, the same diet failed
to show any hypoglycemic effect in alloxanized rats (175 mg/kg SC)
indicating that plant acts through release of insulin (Singh et al.,
1975). Powdered seeds of A. arabica administered in doses of
2, 3 and 4 gm/kg body weight exerted a significant hypoglycemic
effect in normal rabbits by initiating the release of insulin from
pancreatic beta cells. No acute toxicity and behavioral changes were
observed at these doses (Wadood et al., 1989).
Oral administration of aqueous decoction of Aegle marmelos root bark
(1 ml/100 gm) showed hypoglycemic effect which was maximum (44%) at
3 h in normal fasted rats. In addition, the same extract completely
prevented peak rise of blood sugar at 1 h in OGTT. The hypoglycemic
activity was reduced upon storage of extract (Karunanayake et al.,
1984). Aqueous extract of the leaves (1 gm/kg for 30 days)
significantly controlled blood glucose, urea, body weight,
liver glycogen and serum cholesterol of alloxanized (60 mg/kg
IV) rats as compared to controls and this effect was similar to
insulin treatment (Ponnachan et al., 1993). When fed as aqueous leaf
extract (1 gm/kg/day) to STZ (45 mg/kg IV) diabetic rats for 2
weeks, it decreased malate dehydrogenase levels (an enzyme known to
increase in diabetes) in comparison to diabetic controls. The
extract was equi-effective in comparison to insulin in restoring
blood glucose and body weight to normal levels (Seema et al., 1996).
Aqueous leaf extract administered orally for 28 days also normalized
STZ (45 mg/kg body weight) induced histo-pathological alterations in
the pancreatic and kidney tissues of rats (Das et al., 1996).
Various ether soluble fractions of onion as a single oral dose (0.25
mg/kg) showed significant hypoglycemic effect in normal fasted
rabbits. Ether extract showed most potent hypoglycemic action (Augusti,
1973). Petroleum ether insoluble fraction of the ether extract of
dried onion powder (100 mg/kg) given orally for 7 days to
alloxanized (180 mg/kg) diabetic rabbits caused a significant
anti-hypoglycemic effect (Mathew and Augusti, 1975). In a
preliminary study of seven different fractions obtained from onion
bulb, only petroleum ether and chloroform extracts significantly
lowered blood sugar in OGTT (2 mg/kg) in rabbits (Gupta, 1977).
Administration of a sulphur containing amino acid isolated from
A. cepa, called S-methyl cysteine sulphoxide (SMCS) to
alloxanized rats significantly controlled blood glucose and lipids
in serum and tissues, and normalized the activities of liver
hexokinase, glucose 6-phosphatase and HMG CoA reductase. The effect
was comparable to that of glibenclamide and insulin (Kumari et al.,
Oral administration of 0.25 mg/kg of ethanol, petroleum ether, ethyl
ether extract of Allium sativum causes 18.9, 17.9, 26.2%
reduction in blood sugar in alloxan- diabetic rabbits (150 g/kg IV)
(Jain and Vyas, 1975). Oral administration of 0.25 gm/kg allicin
(isolated from A. sativum) produced hypoglycemia comparable to
tolbutamide in mildly diabetic animals (Mathew and Augusti, 1973).
Pretreatment with aged garlic extract (AGE) in stress induced
hypoglycemia model of mice significantly prevented adrenal
hypertrophy, hyperglyce-mia and elevation of cortisone without
altering serum insulin levels. The efficacy of AGE was the same as
that of diazepam. Thus, AGE may prevent stress-induced risk of DM
and its progression (Kasuga et al., 1999). Administration of S-allyl
cysteine sulphoxide (SACS), a sulphur containing amino acid,
significantly decreased the concentration of serum lipids,
blood glucose and activities of serum enzymes like alkaline
phosphatase, acid phosphatase and lactate dehydrogenase and liver
glucose 6-phosphatase. It also significantly increased liver and
intestinal HMG CoA reductase activity and liver hexokinase activity
(Sheela and Augusti, 1992). In another study, oral administration of
SACS to alloxan-diabetic rats for one month ameliorated glucose
intolerance, weight loss, depletion of liver glycogen in diabetic
rats in comparison to glibenclamide and insulin (Sheela et al.,
or Aloe barbadensis
It is used in Ayurveda for managing painful conditions and is also
mentioned in folk medicine of Arabian Peninsula for management of
diabetes. Extracts of aloe gum effectively increased glucose
tolerance in both normal and diabetic rats (Al-Awadi and Gumma,
1987). Chronic but not single administration of the exudates of the
leaves of A. barbadensis showed significant hypoglycemic
effect in alloxan-diabetic mice. However, single as well as chronic
administration of the bitter principle showed significant
hypoglycemic effect in the same model. The hypoglycemic effect of
single dose of the bitter principle was extended over a period of 24
h with maximum hypoglycemia observed at 8 h while chronic
administration (exudates twice daily and the bitter principle once a
day for 4 days) showed maximum reduction in plasma through glucose
level at the 5th day. Hypoglycemic effect of A. vera and its
bitter principle is mediated through stimulation of synthesis and/or
release of insulin from the beta-cells of Langerhans (Aiabnoor,
It is also used in folk medicine as a treatment for DM in parts of
South India.26 Oral administration of methanol extract of aerial
parts A. pallens showed a dose-dependent (100, 500 and 1000 mg/kg)
anti-hyperglycemic effect in glucose fed hyperglycemic and all
oxanized rats (60 mg/kg IV). The effect was moderate in fasted
normal rats but more in diabetic rats (Subramonium et al., 1996).
An epidemiological study has shown that nitrosamines released during
betel chewing may contribute to the risk of developing NIDDM (Mannan
et al., 2000). Subcutaneous administration of alkaloid fraction of
A. catechu (0.05-0.5 mg/kg) in alloxanized rabbits (140 mg/kg of
body weight) had shown significant hypogly-cemic effect lasting for
4-6 h (Chempakam, 1993).
Alcoholic extract of Azadirachta indica showed hypoglycemic
and anti-hypoglycemic effect in normal, glucose fed and STZ diabetic
rats (Chattopadhyay et al., 1987). The plant exerts its
pharmacological activity independent of its time of administration,
that is, either prior or after alloxan administration (Khosla et
al., 2000). The plant blocks the action of epinephrine on glucose
metabolism, thus increasing peripheral glucose utilization (Chattopadhyay,
1996). Bitter principles – nimbin, nimbinin and nimbidin – were
isolated from this plant.
Various glycosides isolated from the root extract of B. vulgaris
have been shown to increase glucose tolerance in OGTT conducted in
rats (Yoshikawa et al., 1996). In addition, the extract also
inhibited non-enzymatic glycosylation of skin proteins in STZ
diabetic rats (Tunali et al., 1998).
The leaf extract of the plant has been shown to exert significant
anti-hyperglycemic effect in alloxanized rabbits possibly by
pancreatic cells stimulating action as the plant was effective in
only mild to moderate and not in severe diabetes (Puri and Baral,
A C-flavonol glucoside isolated from B. ceiba leaves called as
Shamimin has been shown to exert significant hypoglycemic activity
at the dose of 500 mg/kg in rats (Saleem et al., 1999). The extract
was lethal in rats at 500 mg/kg but not in mice even up to 1 gm/km
Oral feeding of B. juncea diet (10% w/w) for 60 days to
normal rats led to significant hypoglycemic effect. This effect was
attributed to stimulation of glycogen synthetase (leading to
increase in hepatic glycogen content) and suppression of glycogen
phosphorylase and other gluconeogenic enzymes (Khan et al., 1995).
The aqueous and alcoholic extract of C. bonducella seeds
exhibited significant hypoglycemic and antihyperglycemic
activities in normal and STZ hyperglycemic rats.
However, aqueous extract was associated with prolonged hypoglycemia
as compared to
ethanolic extract. Hypolipidemic activity has also been described
(Sharma et al., 1997).
It is also used in Panamanian folk medicine for the treatment of
diabetes. A single dose of un-roasted seeds of C. cajan
administration as a 60 and 80% diet to normal and alloxanized mice
caused a significant reduction in the serum glucose levels after 1-2
h and a significant rise at 3 h. On the other hand, roasted seeds
administration caused a significant increase in the serum glucose
levels during a 3 h experimental period. Roasting of seeds at high
temperature for 30 min resulted in the total loss of hypoglycemic
principle but not the hyperglycemic principle present in the seeds (Amalraj
and Ignachimuthu, 1998). Cooked diet of C. cajan has also
shown significant hypoglycemic effect in healthy human volunteers (Panlasigui
et al., 1995).
Oral feeding of diet containing (30%) C. decidua fruit powder
for 3 weeks to alloxanized (80 mg/kg IP) diabetic rats (blood
glucose, 450 mg %) showed significant hypoglycemia (blood glucose,
120-130 mg %) (Yadav et al., 1997).
The fruit of this plant is traditionally used as anti-diabetic in
Mediterranean part of the World. Aqueous extract of its fruit showed
dose-dependent increase in insulin release from isolated islets (Abdel-Hassan
et al., 2000). Oral administration of aqueous extract (300 mg/kg) in
normal rabbits significantly reduced plasma glucose after 1 h and
highly significant reduction after 2, 3, and 6 h. Glycosidic extract
(50 mg/kg) was more effective in lowering fasting glucose as
compared to alkaloid extract. Graded doses (10, 15 and 20 mg/kg) of
saponin also reduced plasma glucose concentration in alloxanized
rabbits. Thus, saponins and glycosidic components of C.
colocynthis are responsible for its hypoglycemic effect (Abdel-Hassan
et al., 2000).
It is used in Ayurveda and Unani system of medicine for treatment of
diabetes, skin eruptions, tongues sore, earache, etc (Chopra et al.,
1956). Feeding of water soluble alkaloid extract of C. indica
leaves to normal fasting guinea pigs showed hypoglycemic
activity of short duration and the effect was attributed to the
presence of β-sitosterol (Mukherjee et al., 1972). Oral
administration of pectin isolated from C. indica fruit showed
a significant hypoglycemic action in normal rats due to stimulation
of glycogen synthetase activity and reduction of phosphorylase
activity (Kumar et al., 1993).
Oral administration of 500 mg/kg of C. indica leaves showed
significant hypoglycemia in alloxan-diabetic dogs (45 mg/kg IV) and
increased glucose tolerance in normal and diabetic dogs (Singh et
al., 1985). Oral administration of ethanolic extract of C. indica
to normal rats significantly lowered blood sugar in fasted model and
depressed the peak value in glucose loaded model (Chandrasekar et
al., 1989). Oral feeding of ethanol extract of the leaves (200
mg/kg) to 18 h fasted rats and STZ diabetic rats led to lowering of
blood sugar by 23 and 27%, hepatic glucose-6-phosphatase by 19 and
32% hepatic fructose-1,6-bisphosphatase by 20 and 30%, respectively,
as com-pared to controls (Shibib et al., 1993). Oral administration
of water soluble alkaloid fraction, chloroform extract and alcoholic
fraction (100 mg/kg) reduced fasting blood glucose of guinea pig by
29.3, 34.5 and 36.3%, respectively. Blood glucose was reduced by 25
and 21% by chloroform extract and alkaloid fraction, respectively,
in OGTT (1 gm/kg) conducted on rats (Mukherjee et al., 1972).
Beneficial effects of leaves of C. indica have also been
shown in a double-blind control trial controlling 16 patients with
uncontrolled maturity onset diabetes and 16 controls. Treatment was
given for 6 weeks and 10 patients showed marked improvement in their
glucose tolerance (Azad et al., 1979). In a clinical study (n=30),
oral administration of dried extract of C. indica (500 mg/kg
for 6 weeks) significantly restored the raised activity of
lipoprotein lipase and the levels of G-6 phosphotase and LDH, which
are otherwise increased in the severe diabetics. This action of the
plant extract was akin to that of insulin (Kamble et al., 1998). As
a single oral dose, the plant extract has been shown to exert
beneficial hypoglycemic effect in experimental animals and human
diabetic subject possibly through an insulin screening effect or
through influence of enzymes involved in glucose metabolism. It was
suggested that the hypoglycemic effect of C. indica are
partly mediated through suppression enzyme glucose-6-phosphotase (Hossain
et al., 1992).
The rhizome of C. caesia is used traditionally by the people
of Manipur (Warjeet et al., 2006).
It is a lofty tree of about 90 cm in height and is grown in
various parts of India. Aqueous extract of (0.5 gm/L of solution) of
euccalyptus increased peripheral glucose utilization in the mouse
abdominal muscle and stepwise enhancement of insulin secretion from
the clonal pancreatic beta cell line by 70-160% (Gray and Flatt,
1998). Administration of E. globulus leaves diet (6.25% w/w)
for 12 days to normal rats did not result in hypoglycemia. In
addition, STZ administration to these pre-treated rats did not
produce hyperglycemia as severely as it was seen in controls. In
addition, pre-treated rats also showed less polydypsia and body
It belongs to the family Myrtaceae. The fruits, that is, the seeds
and the pulp are used as antidiabetics in Indian medicine since
ages. The aqueous and alcoholic extract of seeds exhibited
significant decrease in plasma glucose levels, upon chronic
administration in diabetic rats (Grover et al., 200; Grover et al.,
The possible mechanism suggested is the extract-induced enhancement
of serum insulin levels by the pulp extract. The active principles
isolated were a peptidoglycan, composed of 7-amino acids; and an
oligosaccharide. It is found that the peptideglycan, due to its
nature is not easily degraded. Also, modification of insulin by
sugars might confer resistance to enzymatic degradation, while
retaining the hypoglycemic activity of insulin. However, the
structures of the two compounds obtained from the extract still
remain to be elucidated (Kelkar, 1996).
The decoction of the leaves of the plant is used traditionally by
the people of Manipur (Warjeet and Reena, 2007).
It is a large bushy shrub cultivated in garden. It is also
distributed in Southern Asia, Africa, and in South America. Oral
feeding of ethanol extract of the leaves of E. uniflora to
mice has been shown to contain plasma glucose levels during OGTT and
plasma triglyceride level in oral corn oil tolerance test (Arai et
al., 1999). Few fractions isolated on the basis of polarity and
molecular size from the ethanolic extract of the leaves of E.
uniflora have shown positive effects in OGTT conducted in mice.
In addition, all fractions except one showed dose-dependent
inhibitory effect on the lipase activity and these effects were
apparently due to the inhibition of the
decomposition of carbohydrates and fats in the intestine (Arai et
A very large tree distributed throughout India from sea level to
1,200 m. A glucoside isolated from the bark of F. bengalenesis
showed more potent hypoglycemic action as compared to crude
ethanolic extract and the activity was half of tolbutamide (Augusti,
1975). Oral administration of bark extract showed significant
anti-hyperglycemic effect in STZ diabetic rats by raising serum
insulin levels or inhibiting insulinase activity in liver and kidney
(Avhrekar et al., 1991). Oral administration of leucopelargonidin
derivative isolated from bark of F. bengalenesis exerts
significant hypoglycemic activity in normal and moderately
alloxanized diabetic dogs (Augusti et al., 1994). A leucocyanidin
derivative isolated from the bark of F. bengalenesis was
hypoglycemic in normal rats.
Combination of single dose of this chemical and low dose insulin
controlled diabetes in alloxanized rats as effectively as high dose
of insulin. In addition, long term treatment with this combination
showed equal response to double dose of insulin in respect to body
weight, urine and blood sugar along with amelioration of serum
cholesterol and triglyceride (Kumar et al., 1994). The other
glycoside (pelargonidin derivative) isolated from bark decreased
fasting blood glucose by 19% and improved glucose tolerance by 29%
in moderately diabetic rats at the dose of 250 mg/kg. In comparison,
glibenclamide (2 mg/kg) showed 25 and 66% reduction, respectively,
versus controls (Cherian et al., 1992). Treatment with the same
glycoside (100 mg/kg/day) for one month reduced the fasting blood
glucose levels to almost half of the pretreatment levels. Glucose
tolerance improved by 15% in glycoside treated group versus 41% in
glibenclamide treated group (0.5 mg/kg/day).
In addition, pelargonidin was more potent than leucocyanidin in
stimulating in vitro insulin secretion by beta cells (Cherian et
al., 1992). Another glycoside, leucopelargonidin derivative
possesses significant hypoglycemic, hypolipidemic and serum insulin
raising effects in moderately diabetic rats (Cherian et al., 1993).
Upon single administration of 0.2-1.8 gm/kg and 100, 250, 500
mg/kg/day of the extract for one month in experimental animals, no
lethality and toxic effects were observed.60 Leucodelphinidin (250
mg/kg) also showed hypoglycemic action equal to that of
glibenclamide (2 mg/kg) in normal and alloxan-diabetic rats.
However, in OGTT, it was less effective as compared to glibenclamide
(2 mg/kg) Geetha et al., 1994).
The traditional use of F. hispida is the use of the bark in the
treatment of DM. It is believed that the bark should be peeled out
upward from the bottom of the plant and that peeling out of bark in
downward manner is not effective in the treatment of the disease (Warjeet
and Bimola, 2008). The important active components of F. hispida are
The leaves of Gymnema sylvestre find use as antidiabetic remedy in
ancient Indian medicine since 2000 years. The extract of leaf
inhibited glucose absorption in small intestine of rats.
Kigelia pinnata DC
The decoction of the fruits of the plant is widely used for curing
diabetes in Manipur (Bimola, 2006). The compounds isolated are found
to be 7-hydroxyeuconomic acid, 7-hydroxyviteoid, 10-deoxyeucommidol,
Melothria purpusila Cogn.
The decoction of the whole plant is used. Melothria purpusila is
also used for curing jaundice (Warjeet et al., 2005).
Smilax lanceaefolia Roxb.
The rhizome of Smilax lanceaefolia is used, not only for diabetes
but also for curing urinary calculi (Warjeet and Brajeshwari, 2010).
Mechanisms of action of herbal anti-diabetics
The breakdown of food into simple sugars that are absorbed into the
blood stream begins in the mouth, where salivary amylases attack the
long-chain, molecular carbohydrate components, releasing oligosugars.
Further digestion of food particles occurs in the stomach and
especially in the small intestine. When digestion is complete, the
monosaccharides enter the blood vessels of the intestinal villi.
Although, insulin release from the pancreas and sugar storage by the
liver maintain sugar and salt balance in our body, any problem in
the production or regulation of the hormones will manifest itself
with problems with blood-sugar and fluid/salt imbalances. Herbal
anti-diabetics are found to have properties of releasing of insulin
from islet of langerhans and as an insulin sensitizer.
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