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Int J Diabetes & Metabolism (2006) 14: 1-25Review
Medicinal plants with potential antidiabetic activity - A review of ten years of herbal
medicine research (1990-2000)
Mohamed Bnouham*, Abderrahim Ziyyat, Hassane Mekhfi, Abdelhafid Tahri, Abdelkhaleq Legssyer
Laboratory of Cellular Physiology and Pharmacology, Department of Biology, University of Mohamed the First, Faculty of
Sciences, BP. 524, 60000 Oujda, Morocco
____________________________________________________________________________________________________
Abstract
Medical plants play an important role in the management of diabetes mellitus especially in developing countries where
resources are meager. This review presents the profiles of plants with hypoglycaemic properties, reported in the literature
from 1990 to 2000. The profiles presented include information about the scientific name, family, methodology used, the
degree of hypoglycaemic activity and the active agents. The large number of plants described in this review (176 species
belonging to 84 families) clearly demonstrated the importance of herbal plants in the treatment of diabetes. It also shows the
effort to isolate new potential antidiabetic agents. The plant families, including the species (sp), most studied for their
confirmed hypoglycaemic effects include: Leguminoseae (11 sp), Lamiaceae (7 sp), Liliaceae (8 sp), Cucurbitaceae (7 sp),
Asteraceae (6 sp), Moraceae (6 sp), Rosaceae (6 sp), Euphorbiaceae (5 sp) and Araliaceae (5 sp). The most studied species
are: Citrullus colocynthis (Opuntia streptacantha Lem. (Cactaceae), Trigonella foenum greacum L. (Leguminosea),
Momordica charantia L. (Cucurbitaceae), Ficus bengalensis L. (Moraceae), Polygala senega L. (Polygalaceae), and
Gymnema sylvestre R. (Asclepiadaceae). Many studies have confirmed the benefits of medicinal plants with hypoglycaemic
effects in the management of diabetes mellitus. The effects of these plants may delay the development of diabetic
complications and correct the metabolic abnormalities. Moreover, during the past few years some of the new bioactive drugs
isolated from hypoglycaemic plants showed antidiabetic activity with more efficacy than oral hypoglycaemic agents used in
clinical therapy. (Int J Diabetes Metab 14: 1-25, 2006)
Keywords: Hypoglycaemic, antidiabetic, medicinal plants, diabetes mellitus, pharmacognosy
Introduction
experimental procedures, such as casual surveys or folk
The aim of this review is to collate all available data on
medicine 4,-6-9 are not reported. Moreover, studies based on
plants with hypoglycaemic effects reported in the Medline
preparations of mixtures of plants with unknown origin
(PubMed) during the 1990-2000 period. This review and
were not considered in the present review.
those of Ivorra et al. 1 and Atta-Ur-Rahman2 show the
importance and the interest placed on medicinal plants in
Several medicinal plants have been used as dietary adjunct
the drive to demonstrate their antidiabetic effects and to
and in the treatment of numerous diseases without proper
isolate the bioactive agents.
knowledge of their function. Although phytotherapy
continues to be used in several countries, few plants have
Many ethnobotanical surveys on medicinal plants used by
received scientific or medical scrutinity. Moreover, a large
the local population have been performed in different parts
number of medicinal plants possess some degree of toxicity.
of the world including Morroco, Saudi Arabia, Taiwan, and
For example, it was reported that about one third of
Trinidad andTobogo.2-5,-8-9 Several plant species have been
medicinal plants used in the treatment of diabetes are
described as hypoglycaemic. These inclde Opuntia
considered to be toxic.11
streptacantha Lem, Trigonella foenum graecum L,
Momordica charantia L, Ficus bengalensis L, Polygala
senega L., Gymnema sylvestre R., Allium sativum, Citrullus We believe that the list of medicinal plants presented in this
colocynthis, myrrh, black seeds, helteet, fenugreek, aloe and review is useful to researchers, as well as practitioners. This
Artemisia.2-5 Other species are less well known. list is best used only as a preliminary screening of potential
antidiabetic plants, not as a definitive or complete list of
hypoglycaemic plants.
In the present review, interest is focused on experimental
studies performed on hypoglycaemic plants and their
The list of potential hypoglycaemic plants is presented in
bioactive components. Studies which did not use
the following paragraphs. The scientific name of the plant,
___________________________________
Received on: 11/7/05
the family and the name of the country in which they are
Accepted on: 14/2/06 available are indicated. The description of methods used in
Correspondence to: Dr. Mohamed Bnouham, Department of the experiments, model animals, and the degree of
Biology, Faculty of Sciences, University of Mohamed the First, hypoglycaemia, doses, toxicity and active ingredients are
BP. 524, 60000 Oujda, Morocco, Fax: 212 6 50 06 03, E mail: also included. Plants which did not show any significant
bnouham@sciences.univ-oujda.ac.ma hypoglycaemic effect were not included.
1
,M Bnouham et al
Acanthaceae comparable with that of tolbutamide19. Three suspension
Oral administration of the extract of Asteracantha longifolia cultures of C. rosea were obtained from three different cell
Nees. (20 g/kg of starting material) can significantly lines (CWS, CW-A and CWS-G). In the production
improve glucose tolerance in healthy human subjects and medium, the first cell line produced 0.1 % ajmalicine and
diabetic patients.12 the cell extract caused a 71 % decrease in glycaemia in
diabetic rats. In contrast, in the growth medium, CWS
Amaranthaceae produced trace amounts of alkaloids and the extract did not
Oral administration of 2, 3, and 4 g/kg of Achyranthes show any anti-diabetic activity. The CWA cell line
aspera L produced a significant dose-related hypoglycaemic synthesized 0.036 % ajmalicine. The extract had no
effect in normoglycaemic and alloxan-induced diabetic hypoglycaemic effect while in the growth medium the cells
rabbits. In these animals, water and methanol extracts also produced trace amounts of alkaloids and the extract induced
decreased blood sugar levels. The plant may act by an 86 % decrease in blood sugar. The CWS-G cell line did
providing certain necessary elements like calcium, zinc, not produce significant levels of alkaloids and had no
magnesium, manganese and copper to the beta-cells.13 hypoglycaemic effect.20
Anacardiaceae The extract of Rhazya stricta Decne at oral doses of 0.5,
The antidiabetic activity of Mangifera indica L(Mango) was 2.0 and 4.0 g/kg reduced glycaemia 1 h (2 and 4 g/kg) and
seen when an extract of the leaves of M indica was given to 2 h (4 g/kg) after administration to streptozotocin-diabetic
rats 60 min before the glucose. The hypoglycaemic effect of rats. The insulin concentration increased 1, 2 and 4 h after
the aqueous extract was compared with that of an oral dose administration of the extract at 2 and 4 g/kg. Treatment of
of chlorpropamide (200 mg/kg). The hypoglycaemic action control animals with the extract did not affect glycaemia,
of this plant may be due to a reduction in the intestinal insulin or glucagon levels for up to 4 h after the
absorption of glucose.14 administration of the extract. Simultaneous treatment of
healthy and diabetic rats with the extract (0.5, 2.0 and 5.0
Apiaceae g/kg) and glibenclamide (5.0 mg/kg) exacerbated the
Male Swiss mice were orally loaded with glucose after the effects on glucose, insulin and glucagon. At doses of 0.5,
extracts of Daucus carota L.had been given by oral 2.0 and 4.0 g/kg/day for 6 consecutive days the glycaemia
loading. The extract of Daucus carota L.was prepared by was reduced by approximately 6, 8 and 30 %,
boiling the dried material with water or macerating it with respectively.21
80 % ethanol. It was shown that the extract improved the
glucose tolerance.15 Araliaceae
Ginseng polypeptides (GPP) isolated from the root of
Seeds of Coriandrum sativum L(Coriander)., when supplied Panax ginseng Mey. (Asiatic ginseng)decreased the level
in the diet (6.25 % by weight) and infusion (1 g/400 ml) in of blood sugar and liver glycogen when injected i.v. to rats
place of drinking, reduced the hyperglycaemia during the at doses of 50-200 mg/kg without affecting total blood
development of streptozotocin-induced diabetes in mice.16 lipid concentrations. When mice were injected
The antihyperglycaemic effect Cuminum cyminum L.was subcutaneously with daily doses of 50 and 100 mg/kg for 7
studied in healthy rabbits subjected to weekly subcutaneous successive days, GPP was also found to decrease blood
glucose tolerance tests after gastric administration of water, glucose and liver glycogen and stimulated the release of
tolbutamide or a traditional preparation of the plant. The insulin. In addition, GPP was found to decrease
results showed that the C. Cyminum significantly decreased hyperglycaemia induced experimentally by injection of
the area under glucose tolerance curve and the adrenaline, glucose and alloxan.22-23 The oral
hyperglycaemic peak.17 administration of the water extract of Ginseng Radix (GR)
to normal and adrenaline-induced hyperglycaemic mice
Oral administration of the flavonoids content (8%) of the caused a significant decrease in blood glucose level 4 h
seeds of Cuminum nigrum caused a significant blood after its administration. The hepatic content of the
glucose lowering at a dose range of 0.5 to 1.5 g/kg, both in facilitative glucose transporter isoform 2, liver type glucose
normoglycaemic and alloxan-induced diabetic rabbits. The transporter (GLUT 2) protein significantly increased in the
maximum of decrease in glycaemia was obtained within 4-8 orally GR-treated healthy and adrenaline-induced
h; the normal level of glycaemia was reached within 24 h of hyperglycaemic mice compared to that in the controls.24
drug administration. In contrast, the alkaloids isolated from Recently, ginseng, which is among five crude drugs
C. nigrum (0.01%) had no significant hypoglycaemic effect included in the traditional Chinese prescription, Byakko-
in either normoglycaemic or diabetic rabbits. A high dose ka-ninjin-to, was investigated using genetically obese
of 5g/kg did not produce any adverse effects in a 7-day diabetic KK-CA(y) mice and alloxan-diabetic mice. The
acute toxicity study in rabbits.18 water extract of ginseng, when individually tested,
markedly lowered blood glucose level in diabetic
Apocynaceae animals.25
Oral administration of the aqueous fraction of an alcoholic
extract of leaves of Vinca rosea L. Catharanthus roseus On 4 separate occasions, 10 non-diabetic subjects and 9
Don leads to marked lowering of glycaemia in normal and subjects with type 2 diabetes mellitus received 3 Panax
streptozotocin-induced diabetic rats. This effect was quinquefolius L.(american ginseng)or placebo capsule,
2
, Medicinal plants with potential antidiabetic activity - A review
either 40 minutes before or together with a 25 g oral glucose Gymnema sylvestre R. Br., was administered to type II
challenge (gc). Significant reduction in glycaemia was diabetic patients for 18-20 months as a supplement to the
observed only when ginseng was taken 40 min before gc in conventional oral drugs. During GS4 supplementation, the
non-diabetic subjects and the same result was seen in patients showed a significant reduction in blood glucose,
diabetic subjects.26 glycosylated haemoglobin and glycosylated plasma
proteins, and conventional drug dosage could be decreased.
Saponin isolated from the leaves of Acanthopanax Five of the 22 diabetic patients were able to discontinue
senticosus injected to mice (100, 200 mg/kg, i.p.) decreased their conventional drugs and maintain their blood glucose
experimental hyperglycaemia induced by injection of homeostasis with GS4 alone. These data suggested that
adrenaline, glucose and alloxan, without affecting the levels pancreatic beta cells may be regenerated and/or repaired in
of blood sugar in untreated mice.27 type II diabetic patients on GS4 supplementation. This is
supported by the appearance of raised insulin levels in the
Elatosides E was isolated from the root cortex of Aralia serum of patients after GS4 supplementation.35
elata Seem. (Japanese Angelica)Seem. It was shown to Furthermore, GS4 was administered (400 mg/day) to 27
affect the elevation of plasma glucose levels in an oral patients with insulin-dependent diabetes mellitus (type I).
sugar tolerance test in rats. The structures of elatosides E GS4 therapy appears to enhance endogenous insulin
and F have been elucidated. Moreover, the hypoglycaemic release, possibly by regeneration/revitalisation of the
activity of oleanolic acid and nine oleanolic acid glycosides residual beta cells.36
isolated from the root cortex of this plant were tested.28 Five
new saponins named elatosides G, H, I, J, and K were Investigation of the hypoglycaemic activity of saponin
isolated from a garnish foodstuff “Taranome” which is the constituents from gymnemic acid, a crude saponin fraction
young root shoot of A. elata Seem. Elatosides G, H, and I of G. sylvestre, identified not only two new saponins,
were found to exhibit potent hypoglycaemic activity in the gymnemosides a and b, but also gymnemic acid V as the
oral glucose tolerance test in rats.29 Nine oleanolic acid active principle37 Recently, effects of the water soluble
oligoglycosides were isolated from the cortex of A. elata.30 fraction of an alcoholic extract of G. sylvestre leaves on
glycogen content of isolated rat hemidiaphragm was studied
In order to identify the antidiabetic agent from the stem bark in normal and glucose fed hyperglycaemic rats. In glucose
of Kalopanax pictus Nakai, seven kinds of chemical fed rats, the leaf extract lowered the glycogen content of the
constituents including hederagenin glycosides and phenolic tissue and this effect was amplified by insulin.38
glycosides were isolated. The antidiabetic evaluation of Cryptolepine is a natural product isolated from Cryptolepis
these isolates in streptozotocin-induced diabetic rats showed sanguinolenta. A series of substituted and heterosubstituted
that kalopanax saponin A has a potent antidiabetic activity cryptolepine analogues have been synthesised.
in contrast to a mild activity of hederagenin.31 To Antihyperglycaemic activity was measured in vitro and in a
investigate the relationship between the intestinal bacterial NIDDM mouse model to generate the first structure-
metabolism of kalopanaxsaponin B and H from K. pictus, bioactivity study of the cryptolepine nucleus.39 It was shown
and their antidiabetic effect, kalopanaxsaponin B and H that cryptolepine, an indoloquinolone alkaloid isolated from
were metabolized by human intestinal microflora and the C. sanguinolenta, significantly lowers glucose when given
antidiabetic activity of their metabolites was measured. The orally to diabetic mice. The antihyperglycaemic effect of
main metabolites of kalopanaxsaponin B were cryptolepine leads to a significant decline in blood glucose
kalopanaxsaponin A and hederagenin. The main metabolites concentration, associated with evidence of an enhancement
of kalopanax H were kalopanaxsaponin I and hederagenin. in insulin-mediated glucose disposal. Finally, cryptolepine
Among kalopanaxsaponin B, H and their metabolites, increased glucose uptake by 3T3-L1 cells.40
kalopanaxsaponin A showed the most potent antidiabetic
activity, followed by hederagenin.32 Asteraceae
In vivo bioguided fractionation of the aqueous alcohol
Arecaceae extract of the aerial part of Bidens pilosa Sch. Bip. Var.
The hypoglycaemic effect of neutral detergent fiber from radiata using a model of type 2 diabetes (C57 BL/Ks-db/db
Cocos nucifera L. (coconut) was tested in rats fed 5%, 15% mice) produced two known polyacetylenic glucosides. They
and 30% glucose. Increase in fiber intake caused a were identified as 2-beta-D-glucopyranosyloxyl-1-hydroxy-
significant lowering in glycaemia and serum insulin. 6(E)-tidecene-7, 9, 11-triyne (1) and 3-beta-D-
Moreover, it increases the fecal excretion of Cu, Cr, Mn, glucopyranosyloxyl-1-hydroxy-6(E)-tetradecene-8, 10, 12-
Mg, Zn and Ca. The results suggest the beneficial effect of triyne (2). A 3:2 mixture of glucosides 1 and 2 produced a
inclusion of coconut fiber in the diet.33 significant decrease in blood glucose.41
Intraperitoneal administration of 300 mg/kg of the hexane
Asclepiadaceae extract from Brickellia veronicaefolia A. Gray to diabetic
Oral administration of an extract from Pergularia mice decreased blood glucose levels by 72 %. This extract
tomentosa Span.to normoglycaemic rats produced an administered to normal mice reduced blood glucose levels
hypoglycaemic effect comparable to Daonil.34 by 40 %. The hypoglycaemic effect of this plant extract
confirmed its use in traditional medicine for the treatment of
In humans: GS4 (400 mg/day) extracted from leaves of diabetes.42
3
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