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ISSN0253-71 25
Journal f
Journal of Medicinal and Aromotic Plant Sciences 28 (2006) 612-623
Contribution of indigenous anti-diabetic herbs to alternative medicine of
diabetes mellitus
RAHUL GUPTA, PRIYA SHARMA AND A.M. SAXENA *
Department of Zoology, University of Lucknow, Lucknow-226007, India.
Received 8th March, 2006
ABSTRACT
Recently, diabetes mellitus has become the common disease of
world. Though, advanced technology is being used in modern
treatment system, yet we are far away in exploration of many
aspects and remedy of this disease. Some oral antidiabetic
agents of modern medicine are not up to the mark due to their
harmful side effects. Therefore, search for indigenous
antidiabetic herbs is continued. Indigenous antidiabetic herbs,
today gaining the popularity among alternative forms of
medicine because, it is providing sound health and economic
support to rural and tribal people also.
Key words: Alternative medicine, antidiabetic, diabetes mellitus,
indigenousherbs.
INTRODUCTION
Diabetes mellitus or 'Madhumeha' has been known for
centuries and become common problem of world. It is a disease
related to sweetness, characterized by presence of excessive
sugar in blood and urine due to deficiency in production of
insulin by pancreas or presence of ineffective insulin. The
rapid' growth of this disease is due to heredity, endocrine
imbalance, dietary imprudence, after effects of infection,
obesity, severe and continued mental stress, reduction in
physical labour and big differences in social structure etc.,
which provide a productive atmosphere to diabetes [90]. It is
projected that prevalence of diabetes will affect 221 million
people by the year 2010, which was 151 million in year 2000
[132].
The invention of insulin by Banting & Best (1921) which
is unquestionably the best known remedy for diabetes has
been able to control the hazards of this disease. But the
services of insulin were limited to those who could afford
them, at the same time their repeated dose induced insulin
resistance [12]. The discovery of oral drugs like Su1fonylureas
group by Franke & Fuchs (1955) and biguanides later on
answered many problems connected with this disease [29].
• Corresponding author;
E-mail: anandmsaxena@rediffmail.com
Studies reveal that the synthetic oral hypoglycemic
agents have adverse health effects besides blood sugar
lowering [91]. Therefore, search for anti-diabetic herbs from
traditional medicinal plants has become important [120]. In
Indian system of medicine several herbal remedies had been
tried for the treatment of diabetes mellitus since the time of
'Charaka' & 'Sushruta'.
In current article we have tried to use our best endeavors
to justify the invaluable contribution of indigenous herbs to
alternative medicine of diabetes mellitus.
History oflndigenous herbs in India
During Vedic period Aryans compiled their work related
to herbal remedy in holy Vedas when they came to north India.
References about a number of herbal remedies have been
mentioned in 'Rig-Veda' (about 200 B.C.). In 'Atharva-veda'
(about 200 B.c.) description of medicinal plants has been made
under separate chapter 'Ayurveda'.
It was Charak (about 600 B.C.) who made the scientific
classification of herbal drugs based on remedial properties in
his renowned treatise 'Charaka Sarnhita' (A compendium of
general medicine). In this he described 50 ganas (classes) of
herbal remedies comprising 500 crude drugs [45]. Sushruta
(about 400 B.C.) classified 700 drugs in 37 classes. In this
process Nagarjuna further editing 'Sushruta Samhita',
described the presence of active pharmacological materials of
plants in bark, leaf, flower, fruit and root etc. Similar
pharmacognostic classification was followed by Vagbhata 1
in his compilation' Astanga Sarnhita'. Vagbhata 2 also made
references about the effect of different types of plants in
various diseases [73].
Later on, Srangadhar (about 1400 A.D.) mentioned the
efficacy of herbal drugs and Dhanvantari (about 1500A.D.)
further classified the medicinal plants to avoid the confusion
in identification. Bhavmishra (about 1600 A.D.) also wrote his
monumental work entitled 'Bhavaprakash' and provided
descriptive names of medicinal plants [74] .
612
In recent past from the accumulated knowledge of our
ancient literature useful remedies and herbal drugs against
madhumeha have been identified and compiled by Chopra et
al. [25], Nadkami et at. [77], Satyavati et at. [98], Rahman et
al. [92], Kirtikar and Basu [57] P., S.K. Mukherjee et al. [74],
A.M. Saxena et al. [102], Grover et al. [36], P.K. Mukherjee ei
al. [72] and other workers. They have made remarkable
contribution in rearrangement and reassessment of
indigenous hypoglycemic herbs.
Alternative medicine and diabetes
The central idea of every system of health sciences is
same i.e. to alleviate our pain and cure the maladies. TIle method
of attaining it may be different. In this respect the alternative
medicine is complin1entary to modem system of medicine. The
term alternative medicine means the mode of healing alternate
to modern medicine.
It is well known that diabetes mellitus is not a static but
a dynamic state. Therefore individualization and readjustment
from time to time is necessary. Each case of diabetes mellitus
presents an individual problem. There are a number of
alternative systems of medicine for the treatment of diabetes,
who used the essence of herbs; some of them are Ayurveda,
Siddha, Yunani, Homeopathy etc. Among these 'The science
of life' - Indian Ayurvedic system of medicine existed even
before the birth of modem medicine and uses plants, herbs
and minerals for treatment of diabetes. The healing science of
Ayurveda is based on the total understanding of individual
constitution. Siddha system is one of the oldest systems of
medicine indigenous to India. This is now prevalent mostly in
South India, especially inTamilnadu. In this system of medicine
a number of herbs, minerals and their admixtures have been
used for treatment of diabetes mellitus (Neerazhivu). In India
the admixture of Graeco-Roman and Arabian medicine is
known as 'Yunani' medicine and uses herbs and minerals for
treatment of diabetes. Homeopathy founded and developed
by Samuel Hahnemann (1755-1843) was the earliest important
alternative system of medicine in West. Homeopathy uses
different herbal decoctions for treatment of diabetes [65, 102].
Practical achievements of indigenous trials
Some time before, it was a common thought that oral
hypoglycemic agents are only insulin promoter and have no
specific role in treatment of juvenile diabetes (Type 1diabetes)
because of degeneration of ~-cells of islets of Langerhans.
But it is strange to mention that today some indigenous herbal
drugs responded well in treatment of juvenile diabetes by
promoting the regeneration of~-cells.
Recently many useful herbs have been introduced in
animal experimentation and clinical trials, which induced blood
sugar lowering and repair or regeneration of ~-cells of islets
of Langer hans. Details of some potent indigenous herbs, their
recently reported pharmacological and clinical efficacy on
blood sugar lowering, mechanism of action and toxicity status
are incorporated below:
Aegle marmelos Linn. Coorea (Family: Rutaceae)
Bel or Sirphal (Hindi), Holy Fruit Tree (English)
Aqueous decoction of root bark (1ml/lOOmg) produced
hypoglycemic effect in healthy fasted rats [51].
Antihyperglycemic activity ofleaf extract observed along with
decreased blood urea and cholesterol in alloxan diabetic rats;
the activity attributed to alkaloid constituent of extract [86].
Leaf extract exhibited insulin like activity in diabetic rats [83].
Aqueous leaf extract improved the functional state of
pancreatic cells in streptozotocininduced diabetic rats [27].
Antihyperglycemic activity of leaf extract was observed in
streptozotocin induced diabetic rats [104]. Aqueous extract
(250 & 500mg!k:g, orally) of leaves exhibited hypoglycemic
effect along with increased plasma insulin level in STZ rats.
No sign oftoxicity observed and LDso was greater than IO.Og/
kg when given orally to rats [111]. Leaves extract (250mg/kg,
orally) caused antihyperglycemic activity in glucose induced
hyperglycemic rats; glucose utilization increased by either
enhanced insulin secretion or by glucose uptake stimulation
[96]. Antihyperglycemic activity of aqueous fruit extract
(250mg/kg, twice daily for one month) observed in STZ induced
diabetic albino wistar rats along with decrease in elevated
glucose level and glycosylated haemoglobin level [47].
Antioxidant activity of aqueous extract of fruit (125 & 250mg/
kg, orally for one month) observed in STZ induced diabetic
rats [48]. Hypoglycemic and antioxidant activity ofleaves was
reported in diabetic male albino rats [126], same activities of
plant extract observed in alloxanized rats [95]. Oral
administration offruit extract (125 and 250 mg/kg twice daily
for 30 days) exhibited antidiabetic, antihyperlipidaemic and
antioxidant properties in STZ diabetic rats; also partially
reversed the damage caused by streptozotocin to the
pancreatic islets [46]. (Fig 1)
Fig 1. Aegle marmelos
613
Allium cepa Linn. (Family: Liliaceae)
Pyaj (Hindi), Onion (English)
Ether soluble fraction of onion (0.25mg/kg, orally)
lowered blood glucose level in normal rabbits and has potent
antioxidant activity, which may responsible for hypoglycemic
effect [7]. Onion extract lowered blood sugar in diabetic rabbits
[42]. Controlled blood sugar reported in a clinical study of
diabetic patients by juice of Allium cepa bulb [67]. Onion oil
and synthetic dipropyl disulphide oxide produce significant
hypoglycemic effect [9]. Petroleum ether extract (2g/kg) from
onion bulb produced significant blood sugar lowering in oral
glucose tolerance test of rabbits [37]. S-methyl cystein
sulphoxide (a sulphur containing amino acid) from onion
shown potent hypoglycemic activity at a dose of 200mg/kg
for 45 days to alloxan induced diabetic rats [62]. S-allyl cystein
sulphoxide from onion was also found effective in reducing
glucose level of alloxan induced diabetic rats [114]. Freeze
dried onion powder (3%) prolonged administration with a diet
produced antihyperglycemic, antioxidant and hypolipidemic
Fig 2.'AUium cepa
activity in STZ induced diabetic rats (10]. Callus cultures 0
onion exhibited much higher hypoglycemic potential tha
natural onion bulb [52]. Prolonged administration of onion
with diet produced antioxidant & hypoglycemic effect on
diabetic rats [13]. Antihyperglycemic and antioxidant effect
of Allium cepa juice (OAg/ lOOgb.w. for 4 weeks) was observed
in alloxan induced diabetic rats; along with alleviate liver and
renal damage caused by alloxan [28]. (Fig. 2)
Azadirachta indica A. Juss, (Family: Meliaceae)
Neem (Hindi), Indian lilac tree (English)
Antihyperglycernic and hypoglycemic effect of aqueous
extract reported in diabetic dogs [97]. Aqueous extract of fresh
leaves induced antihyperglycemic activity in normal rats [20]
along with increased peripheral glucose utilization [19].
Hypoglycemic activity of leaf extract observed in normal rat
without effecting serum cortisol level [21]. Blood sugar
lowering activity of crude ethanol extract (250mg/kg, for 2
weeks) reported in alloxan diabetic rats [50]. Antihyperglycemic
activity ofleaf extract observed without altering serum cortisol
Fig 3.Azadirachta indica
614
concentration in STZ induced diabetic rats [32]. Petroleum
ether extract ofkeme1 (2gm/kg b.w.) and husk (O.9gmlkg b.w.)
of neem seeds prevented oxidative stress caused by
streptozotocin in heart and erythrocytes in diabetic rats [38].
Dianex, a polyherba1 formulation consisting of the aqueous
extract of A. indica was well tolerated in laboratory animals
at higher doses (up to 10 g/kg in mice, acute toxicity; up to 2.5
g/kg in rats, subacute toxicity studies for 30 days) without
exhibiting any toxic manifestation [76]. (Fig. 3)
Cinnamomum tam ala (Hamrn.) Nees. & Eberm.
(Family: Lauraceae)
Tejpat (Hindi), Bayberry (English)
Aqueous extract (500mg/kg) of leaves showed
significant blood sugar lowering effect in 18 hours fasted and
glucose loaded rabbits [124]. Hypoglycemic effect ofleaves
(20gm powder,' orally for 15 days) observed in patients of type
2 diabetes mel1itus with release of insulin from pancreatic a-
cells [125]. Hypoglycemic response of Cinnamomum tamala
leaves powder observed in maturity onset (NlDDM) diabetic
patients [15]. Fraction' A' from alcoholic extract (21 Omg/kg)
Fig 4. Cinnamomum tamala
produced significant hypoglycemic response in fasted albino
rats [123]. Hypoglycemic activity of alcoholic extract (250mgl
kg, once daily for two weeks) of leaves reported in alloxan
induced diabetic rats [50]. (Fig. 4)
Coccinia grandis (Linn.) Voigt (Family: Cucurbitaceae)
Syn. Coccina indica (White & Am): Kunderi (Hindi), Ivy
Guard (English)
Fresh leaf succus and alcoholic extract of fresh leaves
lowered blood sugar in guinea pigs [71]. Significant blood
sugar lowering has been observed in patients treated with
homogenized freeze dried leaves [53]. Hypoglycemic activity
of leaf extract (orally) reported in alloxan induced diabetic
dogs [116]. Hypoglycemic activity of ethanol extract (250mg/
kg) of plant observed in fasted, glucose loaded and diabetic
albino rats. However, root extract was effective only in glucose
loaded model [70]. Significant blood sugar lowering effect of
alcoholic extract (250mg/kg, orally) of Coccnia indica
observed in fasted and glucose loaded male albino rats [17].
Hypoglycemic effect of alcoholic extract of leaf in normal fed
and fasted (48h.) rats mediated through suppression of
gluconeogenic enzyme glucose-6-phosphatase [41].
Fig 5. Coccinia grandis
615
Significant blood sugar lowering effect and an increase in
glycogen content of liver observed in normal rats by pectin
isolated from fruits at a dose of200mg/100g/day, orally [60).
Blood sugar lowering effect of alcoholic (60%) leaf extract
(200mg/kg, orally) in diabetic rats by suppressed glucose
synthesis, through depression of glucose-6-phosphatase,
fructose-l-e-biphosphatase and enhanced glucose oxidation
by shunt pathway through activation of glucose-6-phosphate
dehydrogenase (115). Hypoglycemic effect of leaf extract
observed in diabetic patients with an insulin secretogouge
effect [85]. Antihyperglycemic activity of dried extract (500mg/
kg, p.o. for 6 weeks) observed in diabetic patients. Extract
also showed insulin like activity by correcting function of
enzymes in glycolytic pathway and lypolytic pathway [49).
Ethanolic leaf extract (200mg/kg for 45 days) exhibited
significant antioxidant activity [129] and hypolipidemic
activity in streptozotocin induced diabetic rats [82]. (Fig. 5)
Ficus bengalensis Linn. (Family: Moraceae)
Bargad (Hindi), Indian Banyan Tree (English)
When plant extract administered intraperitoneally the
acute LD50 found to be 9.47 g/kg b.w.; however chronic toxicity
test of extract (25 & 250mg/kg) produced reversible hepatic
damage [44]. Blood sugar lowering activity of aqueous extract
of stem bark observed in diabetic patients [43). Hypoglycemic
action of ethanolic extract of F bengalensis and bengalenoside
isolated from it observed in normal and alloxan induced
diabetic rabbits [8). A dimethoxy derivative ofleucocyanidin
3-0-~-D-galactosylcellobioside isolated from bark lowered
blood sugar in normal and moderate diabetic rats along with
increased serum insulin. It also inhibits insulin degradative
processes [61]. Blood sugar lowering activity of bark extract
(orally) observed in STZ induced diabetic rats with enhanced
serum insulin level in normal and diabetic rats [2). Alcoholic
extract (25,50 & 75mg/day/100g b.w.) of stem bark lowered
the blood sugar 47 to 70% as well as maintained normal level
of serum cholesterol, urea and total protein of alloxan diabetic
albino rats [117). Glucoside ofleucopelargonidin isolated from
bark induced hypoglycemic, hypolipidemic and serum insulin
raising effect in moderately diabetic rats [22). A dimethoxy
derivative of pelargonidin 3-0-a-L-rhamnoside (250mg/kg,
single dose study & 100mg/kg/day, long term study) isolated
from bark lowered blood sugar in fasted and glucose loaded
rats [24] along with increased insulin secretion by ~-cells [6).
A 1eucodelphinidine derivative isolated from the bark produced
hypoglycemic activity in normal and alloxan diabetic rats [30).
3-0-a-L-rhanmoside isolated from the bark showed its median
effective dose (EDso) as 100mg/kg with 12% hypoglycemic
action in normal rats (23). Aqueous extract of bark exhibited
hypoglycemic and hypercholesterolemic effect on alloxan
induced mild and severe diabetic rabbits. LDso of this was
found to be l gm/kg, orally for 3 months in rats [39). Treatment
of alloxan diabetic dogs with leucopelargonin derivative
(IOOmg/kg/day for one month) isolated from bark decreased
Fig 6. Ficus bengalensis
fasting blood sugar (34%) and glycosylated haemoglobin
(28%) [26].OFig.6)
Gymnema sylvestre (Willd) R. Br. (Family: Ascelpiadaceae)
Gudmar (Hindi), Periploca of the wood (English)
A water soluble fraction G-54 isolated from G. sylvestre,
when administered orally (400mg/day) to 27 juvenile diabetic
patients lowered their insulin requirement along with reduction
in fasting blood sugar and glycosylated haemoglobin [109].
Fig 7. Gymnema sylvestre
616
Two water soluble fractions GS-3 and GS-4 obtained from
leaves were able to double the islet number and f3-cell number
in pancreas of diabetic rats [108]. Alcoholic extract ofleaves
at a dose of500mg/kg, orally lowered maximum blood sugar in
fasted, glucose loaded and diabetic rats along with insulin
release from pancreatic f3-cells [18]. Hypoglycemic principles
of G. syLvestre isolated from saponin fraction of plant are
referred as gymnemosides and gymnemic acid [131]. Alcoholic
extract stimulate insulin secretion from rat islets of Langer hans
and several pancreatic f3-celllines in absence of other stimulus
[84]. Gymnemic acid IV, obtained from leaves exhibited potent
hypoglycemic activity in STZ induced diabetic mice [121].
Leaf extract of G. sylvestre produced antihyperglycemic effect
in corticosteroid induced diabetes mellitus [31]. Gymnema
syLvestre extract exhibited hypoglycemic activity without
altering the serum cortisol concentration [32]. A polyherbal
formulation (100-500 mg/kglday, orally in acute 6 hand long-
term 6 weeks studies) consisting of the aqueous extracts of
Gymnema syLvestre produced significant hypoglycemic
activity in normal and diabetic rats [76]. Gymnemic acid IV
isolated from the leaves produced hypoglycemic,
antihyperglycemic, glucose uptake inhibitory and gut
glycosidase inhibitory effects [56]. (Fig. 7)
Momordica charantia Linn. (Family: Cucurbitaceae)
Karela (Hindi), Bitter gourd (English)
In a toxicity study all the 10 rats which received karela
juice (15-40c.c./kg, i.p.) became sluggish within one hour and
died in 6 to 18hours [112]. Charantin (50mg/kg, orally) a peptide
resembling insulin isolated from M. charantia lowered blood
sugar(maximum42%at4lh
h.) in rabbits [63]. The polypeptide-
p (0.5 unit/kg, subcutaneously) isolated from fruit, seeds and
tissue showed blood sugar lowering effect in gerbils and
langurs; in clinical trial hypoglycemic effect of polypeptide-p
observed in juvenile and maturity onset diabetic patients with
out apparent side effect [54]. A steroidal saponin, charantin
obtained from M. charantia produced hypoglycemic effect
and act like insulin [79]. Charantin stimulated the release of
insulin and blocked the formation of glucose in blood stream
[80]. The fruit extract (4g/kglday orally for 2 months) produced
hypoglycemic effect and delayed cataract development in
alloxan diabetic rats [119]. Ethanolic extract (200mg/kg) of M.
charantia produced hypoglycemic effect in normal and STZ
diabetic rats as 23% and 27% blood sugar reduction
respectively; this occurred possibly due to inhibition of
glucose-6-phosphatase and fructose-l,6-biphosphatase in
liver and stimulation of hepatic glucose-6-phosphate
dehydrogenase and red cell activities [115]. Two important
constituents of plant, oleanolic acid 3-0-g1ucuronide and
momordin exerted anti-hyperglycemic effect by inhibiting
glucose transport at the brush border of intestine of rat [68].
Juice of fruit exerted anti-hyperglycemic and antioxidant
activity in pancreas of STZ induced diabetic mice [118].
Aqueous extract (200mg/kg, orally for 6 weeks) of fruit and
exercise significantly reduced blood glucose in type 2 diabetic
and hyperinsulinemic (insulin resistance) rats along with
decreased plasma insulin level [69]. Aqueous extract of plant
was found to inhibit primarily the uptake of glucose in male
Swiss albino rats [64]. Aqueous extract of seeds caused
significant reduction in blood glucose, glycosylated
hemoglobin, lactate dehydrogenase, glucose-6-phosphatase,
fructose-Lti-bisphosphatase and glycogen phosphorylase,
and a concomitant increase in the levels of hemoglobin,
glycogen and activities of hexokinase and glycogen synthase
[106]. Bitter gourd contains antidiabetic properties such as
charantin, vicine, and polypeptide-p has the potential to
become a component of dietary supplement for 'diabetic
patients [59]. (Fig. 8)
Fig 8. Momordica charantia
Pterocarpus marsupium Roxb. (Family: Fabaceae)
Vijayasar (Hindi), Indian Malabar (English)
Decoction of bark of P marsupium caused blood sugar
lowering and improvement in glucose tolerance of diabetics
without any side effect [81]. Ethyl acetate soluble fraction of
alcoholic extract of bark lowered blood sugar and caused
changes in alloxan induced f3-cell damage in albino rats [14].
An active constituent (30mg/kg, i.p.) of Pterocarpus
marsupium, (-)-epicatechin (1), has been reported to reverse
hyperglycemia in alloxan diabetic rats [113]. An active
principle (-) epicatechin, from aqueous extract of the bark
increased the cAMP content of the islets which is associated
with the increased insulin release, conversion of pro insulin to
insulin and cathepsin B activity in rats [3]. Phenolic constituent
of plant such as marsupin and pterostilbene significantly
lowered blood glucose level in STZ diabetic rats and the effect
was comparable to metformin [6]. Aqueous extract (lg/kg,
orally) of bark exerted anti-cataract activity in alloxan induced
diabetic rats [127]. An isoflavone, 7-0-a-L-rhamnopyranosyl
isolated from etanolic extract of bark activate glucose transport
PI3 kinase independent pathway in rats [4]. Plant extract
substantially prevented hypertriglyceridaemia and
hyperinsulinaemia (insulin resistance) in non-insulin-
617
dependent diabetes mellitus (NIDDM) patients [35]. Aqueous
extract (250mg/kg, orally) of wood, produced hypoglycemic
effect in acute and sub-acute study [75]. (Fig. 9)
Fig 9.Pterocarpous marsupium
Swertia chirayita (Roxb. ex Flam) Karst. (Family:
Gentianaceae)
Chirata (Hindi), Bitter Stick (English)
Hexane fraction of95% ethanol extract (250mg/kg) of
plant produced blood sugar lowering activity in fasted, glucose
loaded and tolbutamide pretreated animals [lOS]. Hexane
fraction of plant lowered blood sugar at a dose of 250mg/kg
b.w. orally for 28 days in albino rats, along with increased
insulin release and increased glycogen content of liver [16].
Hypoglycemic effect of Swerchirin (1:8 dihydroxy 3:5
dimethoxy xanthone) isolated from hexane fraction of plant
observed at a dose of SOmg/kg, orally in healthy and STZ
treated albino rats [100]. A xanthone isolated from the hexane
fraction of the plant, identified as 1,8-dihydroxy-3,5-
dimethoxyxanthone (swerchirin) produced very significant
blood sugar lowering effect in fasted, fed, glucose loaded,
and tolbutamide pretreated albino rats. The EDso (40% blood
sugar lowering) in CF male albino rats (body weight 140-165
g) reported as 23.1 mg/kgloral [11]. Swerchirin (50 mg/kg, b.w.
orally) induced about 60% (max.) fall in blood glucose by 7 hr
post-treatment. This was associated with depletion of
aldehyde-fuchsin stained ~-granules and immunostained
insulin in the pancreatic islets [10 1].In a comparative study of
structurally different hypoglycemic agents on normal and
streptozotocin induced mild and severe diabetic rats, the
natural product swerchirin was found superior over
tolbutamide [103]. Hypoglycemic activity of alcoholic extract
of plant at a dose of 2S0mg/kg, once daily for two weeks
observed in alloxan induced diabetic rats [50]. (Fig. 10)
SY1JIgiumcumilliLinn. (Family: Myrtaceae)
Syn. Eugenia jambolana Linn.: Jamun (Hindi), Black Berry
(English)
Fruit pulp extract (orally) produced hypoglycemic
activity in normal and STZ diabetic rats by insulin release
mechanism [2]. Jamun seed produced good symptomatic relief
along with regulation of blood sugar in 30 non insulin
dependent diabetes mellitus patients [58]. Aqueous seed
extract (2.5g/kg, b.w. for one month) lowered blood sugar in
alloxan diabetic rats by increased activity of hexokinase and
Fig 10. Swertia chirayita
decreased activity of glucose-S-phosphate in liver [88].,
Aqueous seed extract (2.5 & 5g/kg, b.w. orally for 6 weeks)
produced hypoglycemic, antioxidant activity and increased
haemoglobin content [87]. Lyophilized powder lowered
maximum blood sugar 73.51 % at a dose of200 mg/kg per day
in diabetic mice; it also restored the alteration in hepatic and
skeletal muscle glycogen content and hepatic glucokinase,
hexokinase, glucose-6-phosphate and phosphofructokinase
levels in diabetic mice [33]. After 3 and 6 hOUTS
alcoholic seed
extract injection (i.p. 20mg) reduced the blood sugar level
37.17% and 46.68%, respectively in alloxan diabetic mice. This
was probably due to increased insulin secretion [89]. Fruit
extract (200mg/kg, orally for 50 days) reduced plasma glucose
concentration in STZ induced diabetic mice [33]. Ethanol
extract (IOOmg/kg, b.w. orally) of seed reduced fasting blood
sugar in alloxan induced diabetic rabbits along with
hypolipidemic activity, increased serum insulin, increased
618
glycogen content of liver and muscles and fall in glycosylated
haemoglobin level [110]. Ethanolic seed extract (lOOmg/kg,
b.w.) produced hypoglycemic activity in STZ induced diabetic
rats and exhibited normoglycemia and improved glucose
tolerance [94]. Ethanol extract (lOOgm/kg b.w.) of seed kernel
produced hypoglycemic and hypolipidemic effect in STZ
diabetic rats [93]. At a dose of 5 mg/20g body weight, Syzygium
cumin /-treated mice showed a significant decrease in blood
glucose levels [130].(Fig. 11)
Fig 11. Syzygium cumini
Trigonella foenum-graecum Linn. (Family: Fabaceae)
Methi (Hindi), Fenugreek (English)
Fenugreek seeds and major alkaloid trigonellin exerted
hypoglycemic activity [107]. Fenugreek (2 & 8g/kg, b.w. orally)
produced hypoglycemic effect in normal and alloxan induced
diabetic rats [55). Ethanol extract (0.8g/kg, i.p.) of leaves
significantly reduced blood glucose concentration in alloxan
induced diabetic rats. LDso of i.p. and oral administration of
aqueous leaf extract were 1.9 and lOg/kg, respectively [I]. A
new insulinotropic compound, 4-hydroxyisoleucine isolated
from seeds increased the glucose-induced insulin release
through a direct effect on isolated islets of Langerhans from
both rats and humans [99]. Treatment with fenugreek seeds
powder normalized the alterations like enhanced lipid
peroxidation; it also reduced the susceptibility to oxidative
stress associated with depletion of antioxidants in liver [5].
Seed extract (lg/kg, orally for one month) decreased blood
sugar up to 46.64% in diabetic rats [128]. The soluble dietary
fibre (SDF) fraction of seed (0.5g/kg, orally twice daily for 28
days) exhibited beneficial effect on dyslipidemia and has a
tendency to inhibit platelet aggregation in Type 2 model
diabetic rats [40]. Seed powder (5% orally for 3 weeks) restored
the activity of glutamate dehydrogenase and NAD linked
isocitrate dehydrogenase and D-p-hydro~ybutyrate
dehydrogenase in alloxan diabetic rats. Liver and kidney
damage caused by alloxan also normalized [122]. An
antihyperglycemic amino acid, 4-hydroxyisoleucine 5, isolated
from seeds significantly decreased the plasma triglyceride
levels (33%), total cholesterol (22%) and free fatty acids (14%)
[78]. (Fig. 12)
Fig 12.Trigonellafoenum graecum
Conclusion
The expectation of people from medicine have always
been too high than what medicine can do, but we should
never forget that every system of medicine have their own
limits. Today it is very clear that a holistic approach is needed
to solve the complication of the diabetes, which could be
attained by the combined efforts of alternative medicine and
modern medicine. Therefore the relationship between both
forms of medicine should be always of complementation and
cooperation. Indian traditional medicine is indeed rich in a
vast variety of flora and has ample scope in search of herbal
remedy for diabetes. The cost effectiveness and sustained
agricultural production of many such herbs are yet to be fully
assured. These efforts can provide sound health as well as
economic support to rural and tribal people also. In this regard
even if at least few plant materials stand effective with out
any side effect comparable to commonly used synthetic drugs,
it will be a mile stone in the discovery of relatively cheap and
non toxic drug.
619
ACKNOWLEDGEMENIS
The authors are thankful to Prof. Nirupama Agarwal,
Head, Department of Zoology, University ofLucknow, for her
constant encouragement and guidance in the subject. Authors
are also thankful to Council of Science and Technology, Uttar
Pradesh, Lucknow, for financial assistance for this work.
REFERENCES
I. Abdel Barry JA, Abdel Hassan lA, AI-Hakiem MH. 1997.
Hypoglycaemie and antihyperglycaemic effect of T. foenum
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Contribution of indigenous anti-diabetic herbs to alternate medicine of diabetes mellitus

  • 2. Journal of Medicinal and Aromotic Plant Sciences 28 (2006) 612-623 Contribution of indigenous anti-diabetic herbs to alternative medicine of diabetes mellitus RAHUL GUPTA, PRIYA SHARMA AND A.M. SAXENA * Department of Zoology, University of Lucknow, Lucknow-226007, India. Received 8th March, 2006 ABSTRACT Recently, diabetes mellitus has become the common disease of world. Though, advanced technology is being used in modern treatment system, yet we are far away in exploration of many aspects and remedy of this disease. Some oral antidiabetic agents of modern medicine are not up to the mark due to their harmful side effects. Therefore, search for indigenous antidiabetic herbs is continued. Indigenous antidiabetic herbs, today gaining the popularity among alternative forms of medicine because, it is providing sound health and economic support to rural and tribal people also. Key words: Alternative medicine, antidiabetic, diabetes mellitus, indigenousherbs. INTRODUCTION Diabetes mellitus or 'Madhumeha' has been known for centuries and become common problem of world. It is a disease related to sweetness, characterized by presence of excessive sugar in blood and urine due to deficiency in production of insulin by pancreas or presence of ineffective insulin. The rapid' growth of this disease is due to heredity, endocrine imbalance, dietary imprudence, after effects of infection, obesity, severe and continued mental stress, reduction in physical labour and big differences in social structure etc., which provide a productive atmosphere to diabetes [90]. It is projected that prevalence of diabetes will affect 221 million people by the year 2010, which was 151 million in year 2000 [132]. The invention of insulin by Banting & Best (1921) which is unquestionably the best known remedy for diabetes has been able to control the hazards of this disease. But the services of insulin were limited to those who could afford them, at the same time their repeated dose induced insulin resistance [12]. The discovery of oral drugs like Su1fonylureas group by Franke & Fuchs (1955) and biguanides later on answered many problems connected with this disease [29]. • Corresponding author; E-mail: anandmsaxena@rediffmail.com Studies reveal that the synthetic oral hypoglycemic agents have adverse health effects besides blood sugar lowering [91]. Therefore, search for anti-diabetic herbs from traditional medicinal plants has become important [120]. In Indian system of medicine several herbal remedies had been tried for the treatment of diabetes mellitus since the time of 'Charaka' & 'Sushruta'. In current article we have tried to use our best endeavors to justify the invaluable contribution of indigenous herbs to alternative medicine of diabetes mellitus. History oflndigenous herbs in India During Vedic period Aryans compiled their work related to herbal remedy in holy Vedas when they came to north India. References about a number of herbal remedies have been mentioned in 'Rig-Veda' (about 200 B.C.). In 'Atharva-veda' (about 200 B.c.) description of medicinal plants has been made under separate chapter 'Ayurveda'. It was Charak (about 600 B.C.) who made the scientific classification of herbal drugs based on remedial properties in his renowned treatise 'Charaka Sarnhita' (A compendium of general medicine). In this he described 50 ganas (classes) of herbal remedies comprising 500 crude drugs [45]. Sushruta (about 400 B.C.) classified 700 drugs in 37 classes. In this process Nagarjuna further editing 'Sushruta Samhita', described the presence of active pharmacological materials of plants in bark, leaf, flower, fruit and root etc. Similar pharmacognostic classification was followed by Vagbhata 1 in his compilation' Astanga Sarnhita'. Vagbhata 2 also made references about the effect of different types of plants in various diseases [73]. Later on, Srangadhar (about 1400 A.D.) mentioned the efficacy of herbal drugs and Dhanvantari (about 1500A.D.) further classified the medicinal plants to avoid the confusion in identification. Bhavmishra (about 1600 A.D.) also wrote his monumental work entitled 'Bhavaprakash' and provided descriptive names of medicinal plants [74] . 612
  • 3. In recent past from the accumulated knowledge of our ancient literature useful remedies and herbal drugs against madhumeha have been identified and compiled by Chopra et al. [25], Nadkami et at. [77], Satyavati et at. [98], Rahman et al. [92], Kirtikar and Basu [57] P., S.K. Mukherjee et al. [74], A.M. Saxena et al. [102], Grover et al. [36], P.K. Mukherjee ei al. [72] and other workers. They have made remarkable contribution in rearrangement and reassessment of indigenous hypoglycemic herbs. Alternative medicine and diabetes The central idea of every system of health sciences is same i.e. to alleviate our pain and cure the maladies. TIle method of attaining it may be different. In this respect the alternative medicine is complin1entary to modem system of medicine. The term alternative medicine means the mode of healing alternate to modern medicine. It is well known that diabetes mellitus is not a static but a dynamic state. Therefore individualization and readjustment from time to time is necessary. Each case of diabetes mellitus presents an individual problem. There are a number of alternative systems of medicine for the treatment of diabetes, who used the essence of herbs; some of them are Ayurveda, Siddha, Yunani, Homeopathy etc. Among these 'The science of life' - Indian Ayurvedic system of medicine existed even before the birth of modem medicine and uses plants, herbs and minerals for treatment of diabetes. The healing science of Ayurveda is based on the total understanding of individual constitution. Siddha system is one of the oldest systems of medicine indigenous to India. This is now prevalent mostly in South India, especially inTamilnadu. In this system of medicine a number of herbs, minerals and their admixtures have been used for treatment of diabetes mellitus (Neerazhivu). In India the admixture of Graeco-Roman and Arabian medicine is known as 'Yunani' medicine and uses herbs and minerals for treatment of diabetes. Homeopathy founded and developed by Samuel Hahnemann (1755-1843) was the earliest important alternative system of medicine in West. Homeopathy uses different herbal decoctions for treatment of diabetes [65, 102]. Practical achievements of indigenous trials Some time before, it was a common thought that oral hypoglycemic agents are only insulin promoter and have no specific role in treatment of juvenile diabetes (Type 1diabetes) because of degeneration of ~-cells of islets of Langerhans. But it is strange to mention that today some indigenous herbal drugs responded well in treatment of juvenile diabetes by promoting the regeneration of~-cells. Recently many useful herbs have been introduced in animal experimentation and clinical trials, which induced blood sugar lowering and repair or regeneration of ~-cells of islets of Langer hans. Details of some potent indigenous herbs, their recently reported pharmacological and clinical efficacy on blood sugar lowering, mechanism of action and toxicity status are incorporated below: Aegle marmelos Linn. Coorea (Family: Rutaceae) Bel or Sirphal (Hindi), Holy Fruit Tree (English) Aqueous decoction of root bark (1ml/lOOmg) produced hypoglycemic effect in healthy fasted rats [51]. Antihyperglycemic activity ofleaf extract observed along with decreased blood urea and cholesterol in alloxan diabetic rats; the activity attributed to alkaloid constituent of extract [86]. Leaf extract exhibited insulin like activity in diabetic rats [83]. Aqueous leaf extract improved the functional state of pancreatic cells in streptozotocininduced diabetic rats [27]. Antihyperglycemic activity of leaf extract was observed in streptozotocin induced diabetic rats [104]. Aqueous extract (250 & 500mg!k:g, orally) of leaves exhibited hypoglycemic effect along with increased plasma insulin level in STZ rats. No sign oftoxicity observed and LDso was greater than IO.Og/ kg when given orally to rats [111]. Leaves extract (250mg/kg, orally) caused antihyperglycemic activity in glucose induced hyperglycemic rats; glucose utilization increased by either enhanced insulin secretion or by glucose uptake stimulation [96]. Antihyperglycemic activity of aqueous fruit extract (250mg/kg, twice daily for one month) observed in STZ induced diabetic albino wistar rats along with decrease in elevated glucose level and glycosylated haemoglobin level [47]. Antioxidant activity of aqueous extract of fruit (125 & 250mg/ kg, orally for one month) observed in STZ induced diabetic rats [48]. Hypoglycemic and antioxidant activity ofleaves was reported in diabetic male albino rats [126], same activities of plant extract observed in alloxanized rats [95]. Oral administration offruit extract (125 and 250 mg/kg twice daily for 30 days) exhibited antidiabetic, antihyperlipidaemic and antioxidant properties in STZ diabetic rats; also partially reversed the damage caused by streptozotocin to the pancreatic islets [46]. (Fig 1) Fig 1. Aegle marmelos 613
  • 4. Allium cepa Linn. (Family: Liliaceae) Pyaj (Hindi), Onion (English) Ether soluble fraction of onion (0.25mg/kg, orally) lowered blood glucose level in normal rabbits and has potent antioxidant activity, which may responsible for hypoglycemic effect [7]. Onion extract lowered blood sugar in diabetic rabbits [42]. Controlled blood sugar reported in a clinical study of diabetic patients by juice of Allium cepa bulb [67]. Onion oil and synthetic dipropyl disulphide oxide produce significant hypoglycemic effect [9]. Petroleum ether extract (2g/kg) from onion bulb produced significant blood sugar lowering in oral glucose tolerance test of rabbits [37]. S-methyl cystein sulphoxide (a sulphur containing amino acid) from onion shown potent hypoglycemic activity at a dose of 200mg/kg for 45 days to alloxan induced diabetic rats [62]. S-allyl cystein sulphoxide from onion was also found effective in reducing glucose level of alloxan induced diabetic rats [114]. Freeze dried onion powder (3%) prolonged administration with a diet produced antihyperglycemic, antioxidant and hypolipidemic Fig 2.'AUium cepa activity in STZ induced diabetic rats (10]. Callus cultures 0 onion exhibited much higher hypoglycemic potential tha natural onion bulb [52]. Prolonged administration of onion with diet produced antioxidant & hypoglycemic effect on diabetic rats [13]. Antihyperglycemic and antioxidant effect of Allium cepa juice (OAg/ lOOgb.w. for 4 weeks) was observed in alloxan induced diabetic rats; along with alleviate liver and renal damage caused by alloxan [28]. (Fig. 2) Azadirachta indica A. Juss, (Family: Meliaceae) Neem (Hindi), Indian lilac tree (English) Antihyperglycernic and hypoglycemic effect of aqueous extract reported in diabetic dogs [97]. Aqueous extract of fresh leaves induced antihyperglycemic activity in normal rats [20] along with increased peripheral glucose utilization [19]. Hypoglycemic activity of leaf extract observed in normal rat without effecting serum cortisol level [21]. Blood sugar lowering activity of crude ethanol extract (250mg/kg, for 2 weeks) reported in alloxan diabetic rats [50]. Antihyperglycemic activity ofleaf extract observed without altering serum cortisol Fig 3.Azadirachta indica 614
  • 5. concentration in STZ induced diabetic rats [32]. Petroleum ether extract ofkeme1 (2gm/kg b.w.) and husk (O.9gmlkg b.w.) of neem seeds prevented oxidative stress caused by streptozotocin in heart and erythrocytes in diabetic rats [38]. Dianex, a polyherba1 formulation consisting of the aqueous extract of A. indica was well tolerated in laboratory animals at higher doses (up to 10 g/kg in mice, acute toxicity; up to 2.5 g/kg in rats, subacute toxicity studies for 30 days) without exhibiting any toxic manifestation [76]. (Fig. 3) Cinnamomum tam ala (Hamrn.) Nees. & Eberm. (Family: Lauraceae) Tejpat (Hindi), Bayberry (English) Aqueous extract (500mg/kg) of leaves showed significant blood sugar lowering effect in 18 hours fasted and glucose loaded rabbits [124]. Hypoglycemic effect ofleaves (20gm powder,' orally for 15 days) observed in patients of type 2 diabetes mel1itus with release of insulin from pancreatic a- cells [125]. Hypoglycemic response of Cinnamomum tamala leaves powder observed in maturity onset (NlDDM) diabetic patients [15]. Fraction' A' from alcoholic extract (21 Omg/kg) Fig 4. Cinnamomum tamala produced significant hypoglycemic response in fasted albino rats [123]. Hypoglycemic activity of alcoholic extract (250mgl kg, once daily for two weeks) of leaves reported in alloxan induced diabetic rats [50]. (Fig. 4) Coccinia grandis (Linn.) Voigt (Family: Cucurbitaceae) Syn. Coccina indica (White & Am): Kunderi (Hindi), Ivy Guard (English) Fresh leaf succus and alcoholic extract of fresh leaves lowered blood sugar in guinea pigs [71]. Significant blood sugar lowering has been observed in patients treated with homogenized freeze dried leaves [53]. Hypoglycemic activity of leaf extract (orally) reported in alloxan induced diabetic dogs [116]. Hypoglycemic activity of ethanol extract (250mg/ kg) of plant observed in fasted, glucose loaded and diabetic albino rats. However, root extract was effective only in glucose loaded model [70]. Significant blood sugar lowering effect of alcoholic extract (250mg/kg, orally) of Coccnia indica observed in fasted and glucose loaded male albino rats [17]. Hypoglycemic effect of alcoholic extract of leaf in normal fed and fasted (48h.) rats mediated through suppression of gluconeogenic enzyme glucose-6-phosphatase [41]. Fig 5. Coccinia grandis 615
  • 6. Significant blood sugar lowering effect and an increase in glycogen content of liver observed in normal rats by pectin isolated from fruits at a dose of200mg/100g/day, orally [60). Blood sugar lowering effect of alcoholic (60%) leaf extract (200mg/kg, orally) in diabetic rats by suppressed glucose synthesis, through depression of glucose-6-phosphatase, fructose-l-e-biphosphatase and enhanced glucose oxidation by shunt pathway through activation of glucose-6-phosphate dehydrogenase (115). Hypoglycemic effect of leaf extract observed in diabetic patients with an insulin secretogouge effect [85]. Antihyperglycemic activity of dried extract (500mg/ kg, p.o. for 6 weeks) observed in diabetic patients. Extract also showed insulin like activity by correcting function of enzymes in glycolytic pathway and lypolytic pathway [49). Ethanolic leaf extract (200mg/kg for 45 days) exhibited significant antioxidant activity [129] and hypolipidemic activity in streptozotocin induced diabetic rats [82]. (Fig. 5) Ficus bengalensis Linn. (Family: Moraceae) Bargad (Hindi), Indian Banyan Tree (English) When plant extract administered intraperitoneally the acute LD50 found to be 9.47 g/kg b.w.; however chronic toxicity test of extract (25 & 250mg/kg) produced reversible hepatic damage [44]. Blood sugar lowering activity of aqueous extract of stem bark observed in diabetic patients [43). Hypoglycemic action of ethanolic extract of F bengalensis and bengalenoside isolated from it observed in normal and alloxan induced diabetic rabbits [8). A dimethoxy derivative ofleucocyanidin 3-0-~-D-galactosylcellobioside isolated from bark lowered blood sugar in normal and moderate diabetic rats along with increased serum insulin. It also inhibits insulin degradative processes [61]. Blood sugar lowering activity of bark extract (orally) observed in STZ induced diabetic rats with enhanced serum insulin level in normal and diabetic rats [2). Alcoholic extract (25,50 & 75mg/day/100g b.w.) of stem bark lowered the blood sugar 47 to 70% as well as maintained normal level of serum cholesterol, urea and total protein of alloxan diabetic albino rats [117). Glucoside ofleucopelargonidin isolated from bark induced hypoglycemic, hypolipidemic and serum insulin raising effect in moderately diabetic rats [22). A dimethoxy derivative of pelargonidin 3-0-a-L-rhamnoside (250mg/kg, single dose study & 100mg/kg/day, long term study) isolated from bark lowered blood sugar in fasted and glucose loaded rats [24] along with increased insulin secretion by ~-cells [6). A 1eucodelphinidine derivative isolated from the bark produced hypoglycemic activity in normal and alloxan diabetic rats [30). 3-0-a-L-rhanmoside isolated from the bark showed its median effective dose (EDso) as 100mg/kg with 12% hypoglycemic action in normal rats (23). Aqueous extract of bark exhibited hypoglycemic and hypercholesterolemic effect on alloxan induced mild and severe diabetic rabbits. LDso of this was found to be l gm/kg, orally for 3 months in rats [39). Treatment of alloxan diabetic dogs with leucopelargonin derivative (IOOmg/kg/day for one month) isolated from bark decreased Fig 6. Ficus bengalensis fasting blood sugar (34%) and glycosylated haemoglobin (28%) [26].OFig.6) Gymnema sylvestre (Willd) R. Br. (Family: Ascelpiadaceae) Gudmar (Hindi), Periploca of the wood (English) A water soluble fraction G-54 isolated from G. sylvestre, when administered orally (400mg/day) to 27 juvenile diabetic patients lowered their insulin requirement along with reduction in fasting blood sugar and glycosylated haemoglobin [109]. Fig 7. Gymnema sylvestre 616
  • 7. Two water soluble fractions GS-3 and GS-4 obtained from leaves were able to double the islet number and f3-cell number in pancreas of diabetic rats [108]. Alcoholic extract ofleaves at a dose of500mg/kg, orally lowered maximum blood sugar in fasted, glucose loaded and diabetic rats along with insulin release from pancreatic f3-cells [18]. Hypoglycemic principles of G. syLvestre isolated from saponin fraction of plant are referred as gymnemosides and gymnemic acid [131]. Alcoholic extract stimulate insulin secretion from rat islets of Langer hans and several pancreatic f3-celllines in absence of other stimulus [84]. Gymnemic acid IV, obtained from leaves exhibited potent hypoglycemic activity in STZ induced diabetic mice [121]. Leaf extract of G. sylvestre produced antihyperglycemic effect in corticosteroid induced diabetes mellitus [31]. Gymnema syLvestre extract exhibited hypoglycemic activity without altering the serum cortisol concentration [32]. A polyherbal formulation (100-500 mg/kglday, orally in acute 6 hand long- term 6 weeks studies) consisting of the aqueous extracts of Gymnema syLvestre produced significant hypoglycemic activity in normal and diabetic rats [76]. Gymnemic acid IV isolated from the leaves produced hypoglycemic, antihyperglycemic, glucose uptake inhibitory and gut glycosidase inhibitory effects [56]. (Fig. 7) Momordica charantia Linn. (Family: Cucurbitaceae) Karela (Hindi), Bitter gourd (English) In a toxicity study all the 10 rats which received karela juice (15-40c.c./kg, i.p.) became sluggish within one hour and died in 6 to 18hours [112]. Charantin (50mg/kg, orally) a peptide resembling insulin isolated from M. charantia lowered blood sugar(maximum42%at4lh h.) in rabbits [63]. The polypeptide- p (0.5 unit/kg, subcutaneously) isolated from fruit, seeds and tissue showed blood sugar lowering effect in gerbils and langurs; in clinical trial hypoglycemic effect of polypeptide-p observed in juvenile and maturity onset diabetic patients with out apparent side effect [54]. A steroidal saponin, charantin obtained from M. charantia produced hypoglycemic effect and act like insulin [79]. Charantin stimulated the release of insulin and blocked the formation of glucose in blood stream [80]. The fruit extract (4g/kglday orally for 2 months) produced hypoglycemic effect and delayed cataract development in alloxan diabetic rats [119]. Ethanolic extract (200mg/kg) of M. charantia produced hypoglycemic effect in normal and STZ diabetic rats as 23% and 27% blood sugar reduction respectively; this occurred possibly due to inhibition of glucose-6-phosphatase and fructose-l,6-biphosphatase in liver and stimulation of hepatic glucose-6-phosphate dehydrogenase and red cell activities [115]. Two important constituents of plant, oleanolic acid 3-0-g1ucuronide and momordin exerted anti-hyperglycemic effect by inhibiting glucose transport at the brush border of intestine of rat [68]. Juice of fruit exerted anti-hyperglycemic and antioxidant activity in pancreas of STZ induced diabetic mice [118]. Aqueous extract (200mg/kg, orally for 6 weeks) of fruit and exercise significantly reduced blood glucose in type 2 diabetic and hyperinsulinemic (insulin resistance) rats along with decreased plasma insulin level [69]. Aqueous extract of plant was found to inhibit primarily the uptake of glucose in male Swiss albino rats [64]. Aqueous extract of seeds caused significant reduction in blood glucose, glycosylated hemoglobin, lactate dehydrogenase, glucose-6-phosphatase, fructose-Lti-bisphosphatase and glycogen phosphorylase, and a concomitant increase in the levels of hemoglobin, glycogen and activities of hexokinase and glycogen synthase [106]. Bitter gourd contains antidiabetic properties such as charantin, vicine, and polypeptide-p has the potential to become a component of dietary supplement for 'diabetic patients [59]. (Fig. 8) Fig 8. Momordica charantia Pterocarpus marsupium Roxb. (Family: Fabaceae) Vijayasar (Hindi), Indian Malabar (English) Decoction of bark of P marsupium caused blood sugar lowering and improvement in glucose tolerance of diabetics without any side effect [81]. Ethyl acetate soluble fraction of alcoholic extract of bark lowered blood sugar and caused changes in alloxan induced f3-cell damage in albino rats [14]. An active constituent (30mg/kg, i.p.) of Pterocarpus marsupium, (-)-epicatechin (1), has been reported to reverse hyperglycemia in alloxan diabetic rats [113]. An active principle (-) epicatechin, from aqueous extract of the bark increased the cAMP content of the islets which is associated with the increased insulin release, conversion of pro insulin to insulin and cathepsin B activity in rats [3]. Phenolic constituent of plant such as marsupin and pterostilbene significantly lowered blood glucose level in STZ diabetic rats and the effect was comparable to metformin [6]. Aqueous extract (lg/kg, orally) of bark exerted anti-cataract activity in alloxan induced diabetic rats [127]. An isoflavone, 7-0-a-L-rhamnopyranosyl isolated from etanolic extract of bark activate glucose transport PI3 kinase independent pathway in rats [4]. Plant extract substantially prevented hypertriglyceridaemia and hyperinsulinaemia (insulin resistance) in non-insulin- 617
  • 8. dependent diabetes mellitus (NIDDM) patients [35]. Aqueous extract (250mg/kg, orally) of wood, produced hypoglycemic effect in acute and sub-acute study [75]. (Fig. 9) Fig 9.Pterocarpous marsupium Swertia chirayita (Roxb. ex Flam) Karst. (Family: Gentianaceae) Chirata (Hindi), Bitter Stick (English) Hexane fraction of95% ethanol extract (250mg/kg) of plant produced blood sugar lowering activity in fasted, glucose loaded and tolbutamide pretreated animals [lOS]. Hexane fraction of plant lowered blood sugar at a dose of 250mg/kg b.w. orally for 28 days in albino rats, along with increased insulin release and increased glycogen content of liver [16]. Hypoglycemic effect of Swerchirin (1:8 dihydroxy 3:5 dimethoxy xanthone) isolated from hexane fraction of plant observed at a dose of SOmg/kg, orally in healthy and STZ treated albino rats [100]. A xanthone isolated from the hexane fraction of the plant, identified as 1,8-dihydroxy-3,5- dimethoxyxanthone (swerchirin) produced very significant blood sugar lowering effect in fasted, fed, glucose loaded, and tolbutamide pretreated albino rats. The EDso (40% blood sugar lowering) in CF male albino rats (body weight 140-165 g) reported as 23.1 mg/kgloral [11]. Swerchirin (50 mg/kg, b.w. orally) induced about 60% (max.) fall in blood glucose by 7 hr post-treatment. This was associated with depletion of aldehyde-fuchsin stained ~-granules and immunostained insulin in the pancreatic islets [10 1].In a comparative study of structurally different hypoglycemic agents on normal and streptozotocin induced mild and severe diabetic rats, the natural product swerchirin was found superior over tolbutamide [103]. Hypoglycemic activity of alcoholic extract of plant at a dose of 2S0mg/kg, once daily for two weeks observed in alloxan induced diabetic rats [50]. (Fig. 10) SY1JIgiumcumilliLinn. (Family: Myrtaceae) Syn. Eugenia jambolana Linn.: Jamun (Hindi), Black Berry (English) Fruit pulp extract (orally) produced hypoglycemic activity in normal and STZ diabetic rats by insulin release mechanism [2]. Jamun seed produced good symptomatic relief along with regulation of blood sugar in 30 non insulin dependent diabetes mellitus patients [58]. Aqueous seed extract (2.5g/kg, b.w. for one month) lowered blood sugar in alloxan diabetic rats by increased activity of hexokinase and Fig 10. Swertia chirayita decreased activity of glucose-S-phosphate in liver [88]., Aqueous seed extract (2.5 & 5g/kg, b.w. orally for 6 weeks) produced hypoglycemic, antioxidant activity and increased haemoglobin content [87]. Lyophilized powder lowered maximum blood sugar 73.51 % at a dose of200 mg/kg per day in diabetic mice; it also restored the alteration in hepatic and skeletal muscle glycogen content and hepatic glucokinase, hexokinase, glucose-6-phosphate and phosphofructokinase levels in diabetic mice [33]. After 3 and 6 hOUTS alcoholic seed extract injection (i.p. 20mg) reduced the blood sugar level 37.17% and 46.68%, respectively in alloxan diabetic mice. This was probably due to increased insulin secretion [89]. Fruit extract (200mg/kg, orally for 50 days) reduced plasma glucose concentration in STZ induced diabetic mice [33]. Ethanol extract (IOOmg/kg, b.w. orally) of seed reduced fasting blood sugar in alloxan induced diabetic rabbits along with hypolipidemic activity, increased serum insulin, increased 618
  • 9. glycogen content of liver and muscles and fall in glycosylated haemoglobin level [110]. Ethanolic seed extract (lOOmg/kg, b.w.) produced hypoglycemic activity in STZ induced diabetic rats and exhibited normoglycemia and improved glucose tolerance [94]. Ethanol extract (lOOgm/kg b.w.) of seed kernel produced hypoglycemic and hypolipidemic effect in STZ diabetic rats [93]. At a dose of 5 mg/20g body weight, Syzygium cumin /-treated mice showed a significant decrease in blood glucose levels [130].(Fig. 11) Fig 11. Syzygium cumini Trigonella foenum-graecum Linn. (Family: Fabaceae) Methi (Hindi), Fenugreek (English) Fenugreek seeds and major alkaloid trigonellin exerted hypoglycemic activity [107]. Fenugreek (2 & 8g/kg, b.w. orally) produced hypoglycemic effect in normal and alloxan induced diabetic rats [55). Ethanol extract (0.8g/kg, i.p.) of leaves significantly reduced blood glucose concentration in alloxan induced diabetic rats. LDso of i.p. and oral administration of aqueous leaf extract were 1.9 and lOg/kg, respectively [I]. A new insulinotropic compound, 4-hydroxyisoleucine isolated from seeds increased the glucose-induced insulin release through a direct effect on isolated islets of Langerhans from both rats and humans [99]. Treatment with fenugreek seeds powder normalized the alterations like enhanced lipid peroxidation; it also reduced the susceptibility to oxidative stress associated with depletion of antioxidants in liver [5]. Seed extract (lg/kg, orally for one month) decreased blood sugar up to 46.64% in diabetic rats [128]. The soluble dietary fibre (SDF) fraction of seed (0.5g/kg, orally twice daily for 28 days) exhibited beneficial effect on dyslipidemia and has a tendency to inhibit platelet aggregation in Type 2 model diabetic rats [40]. Seed powder (5% orally for 3 weeks) restored the activity of glutamate dehydrogenase and NAD linked isocitrate dehydrogenase and D-p-hydro~ybutyrate dehydrogenase in alloxan diabetic rats. Liver and kidney damage caused by alloxan also normalized [122]. An antihyperglycemic amino acid, 4-hydroxyisoleucine 5, isolated from seeds significantly decreased the plasma triglyceride levels (33%), total cholesterol (22%) and free fatty acids (14%) [78]. (Fig. 12) Fig 12.Trigonellafoenum graecum Conclusion The expectation of people from medicine have always been too high than what medicine can do, but we should never forget that every system of medicine have their own limits. Today it is very clear that a holistic approach is needed to solve the complication of the diabetes, which could be attained by the combined efforts of alternative medicine and modern medicine. Therefore the relationship between both forms of medicine should be always of complementation and cooperation. Indian traditional medicine is indeed rich in a vast variety of flora and has ample scope in search of herbal remedy for diabetes. The cost effectiveness and sustained agricultural production of many such herbs are yet to be fully assured. These efforts can provide sound health as well as economic support to rural and tribal people also. In this regard even if at least few plant materials stand effective with out any side effect comparable to commonly used synthetic drugs, it will be a mile stone in the discovery of relatively cheap and non toxic drug. 619
  • 10. ACKNOWLEDGEMENIS The authors are thankful to Prof. Nirupama Agarwal, Head, Department of Zoology, University ofLucknow, for her constant encouragement and guidance in the subject. Authors are also thankful to Council of Science and Technology, Uttar Pradesh, Lucknow, for financial assistance for this work. REFERENCES I. Abdel Barry JA, Abdel Hassan lA, AI-Hakiem MH. 1997. Hypoglycaemie and antihyperglycaemic effect of T. foenum graecum lcaf in normal and alloxan induced diabetic rats. J E/hnopharmacology 58: 149-155. 2. Achrckar S, Kakliji GS, Pote MS, Kelkar SM. 199!. Hypoglycemic activity of Eugenia jambolana and Ficus bengalenesis: Mcchanism of action. In Vivo 5: 143-147. 3. Ahmad F, Khan MM, Rastogi AK, Chaubcy M, Kidwai JR. 1991. Effect of (-)-epicatcchin on cAMP content, insulin release and conversion of proinsulin to insulin in immature and mature rat islets in vitro. Indian J Exp Bioi 29: 516-520. 4. 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