Vol. 8(11), pp. 292-303, 22 March, 2014
DOI 10.5897/AJPP2014.3933
ISSN 1996-0816
Copyright © 2014
Author(s) retain the copyright of this article
http://www.academicjournals.org/AJPP
African Journal of Pharmacy and
Pharmacology
Review
The search for new hypoglycemic agents from plants
Patience O. Osadebe
1
, Estella U. Odoh
2
and Philip F. Uzor
1
*
1
Department of Pharmaceutical and Medicinal Chemistry, University of Nigeria, Nsukka, Enugu State, 410001, Nigeria.
2
Department of Pharmacognosy and Environmental Medicine, University of Nigeria, Nsukka,
Enugu State, 410001, Nigeria.
Received 6 January, 2014; Accepted 14 February, 2014
Diabetes mellitus is a serious endocrine disorder that causes millions of deaths worldwide. The
conventional drugs are associated with a number of adverse effects and limitations. In the search for
better alternatives, many medicinal plants have been investigated and a variety of compounds have also
been isolated. In the present review, medicinal plants selected from those that have been investigated
for their antidiabetic potential between the year 2000 and 2013 are presented. The most common
families of plants presented are the Asteraceae, Euphorbiaceae and Gentianaecae. The structures of
some previously isolated compounds with antidiabetic potential are presented. Most of the isolated
antidiabetic principles are alkaloids, flavonoids, amino acid, steroids and organic acids. It was however
discovered that most of the investigations are preliminary in nature. More detailed investigations into
the efficacy, mode of action and safety profile of these plants and the isolated compounds in preclinical
and clinical studies are recommended.
Key words: Antidiabetic plants, hyperglycemia, hypoglycemia, medicinal plants review.
INTRODUCTION
Diabetes mellitus is a chronic disorder characterized by
elevated blood glucose levels and disturbance in
carbohydrate, fat and protein metabolism (Aguwa, 2004).
Diabetic patients experience various vascular complica-
tions such as, atherosclerosis, diabetic nephropathy,
retinopathy and neuropathy (Sheetz, 2002). The 2012
report by the International Diabetes Federation (IDF)
showed that more than 371 million people (8.3% of the
world’s population) had diabetes and the number of peo-
ple with diabetes was increasing in every country, while
4.8 million people died and 471 billion USD were spent
due to diabetes in 2012 (IDF, 2012).
The currently available therapy for diabetes includes
insulin and various oral anti-diabetic agents such as the
sulfonylureas, biguanides, thiazolidinediones and α-
glucosidase inhibitors. These drugs are used as
monotherapy or in combination to achieve better
glycemic control. Each of the oral antidiabetic agents is
however, associated with a number of serious adverse
effects (Moller, 2001; Nwaegerue et al., 2007). Plant-
based drugs have been known to be safe and cheaper.
Before the discovery of insulin by Banting and Best
(1922), the only options were those based on traditional
practices (Ribnicky et al., 2009). Thus the search for
safer and easily available antidiabetic agents among
medicinal plants continues. According to world ethno-
botanical information reports, almost 800 plants possess
antidiabetic potential (Alarcon-Aguilara et al., 1998).
*Corresponding author: E-mail: philuzor4u@yahoo.com.
Author(s) agree that this article remain permanently open access under the terms of the Creative Commons Attribution
License 4.0 International License
Recently, an ethnobotanical survey of the plants used
in the treatment of diabetes mellitus was conducted in
some areas of South-Western Nigeria. The survey
revealed the use of about 132 different plants species
belonging to 56 families in the treatment of diabetes
mellitus (Soladoye et al., 2012). Though these plants are
claimed to possess hypoglycemic properties, most claims
are anecdotal and few have received adequate medical
or scientific evaluation (Bailey and Day, 1989). Several
reviews on the plants used in the management of
diabetes have been reported in the past (Bnouham et al.,
2006; Kavishankar et al., 2011; Akah et al., 2002).
However, information on the nature and source of the
putative hypoglycemic active agents of some of the
plants are scattered. Plant products are known to be rich
in phenolic compounds, flavonoids, terpenoids,
coumarins and other constituents which reduce blood
glucose levels (He et al., 2005; Jung et al., 2006). There
is need therefore to update the current knowledge as
more plants are being investigated and to highlight the
molecular structures and nature of some of the isolated
hypoglycemic agents from plants. Here we present a list
of selected plants which have been investigated for their
hypoglycemic potentials between years 2000 to 2013.
Also presented are the molecular structures and sources
of some of the potential hypoglycemic compounds which
have been isolated from medicinal plants.
Some plants investigated for antidiabetic activity
The first part of the present review work was conducted
by searching the PubMed, Medline and Google scholar
for medicinal plants that have been investigated between
2000 and 2013. Only some of the plants were selected
based on their ethno-botanical importance and the depth
of research on them. The second part of the work
involves the hypoglycemic or antidiabetic plants with their
active principles isolated. Unlike the first part of the work,
the compounds were not necessarily identified in the
period 2000 to 2013. The botanical, family and the
common names of the medicinal plants that have been
investigated for their antidiabetic potential are presented
in Table 1. The most commonly occurring family of plants
listed include Asteraceae (6), Euphorbiaceae (5),
Gentianeacea (5), Brassicaceae (3), Caesalpiniaceae (3),
Lamiaceae (3), Myrtaceae (3), Asclepiadaceae (2),
Convolvulaceae (2), Cucurbitaceae (2), Oxalidaceae (2)
and Papillionaceae (2). The investigations carried out on
the plants have employed several plant extracts
(aqueous, other solvents) in various models such as in
vitro techniques involving enzyme inhibition or isolated
cells, in vivo techniques involving administration (through
oral or parenteral route, in various doses) in normal, che-
mical (alloxan, streptozotocin)-induced or in genetically
modified diabetic animals (mice, rabbits, rats and dogs)
and oral glucose tolerance test (OGTT). The experiments
Osadebe et al. 293
in animals were of acute (within 24 h) or chronic (a few
days to few months) duration. Few of the studies have
been carried out in humans. Toxicity studies and
investigations on the mode of action of the plants are
limited.
Chemical structures of isolated compounds from
antidiabetic plants
The active compounds from the antidiabetic medicinal
plants with their sources are shown in Figure 1. Twenty
eight (28) compounds from different medicinal plants are
shown. They have varied structures but most of them are
alkaloids (11) or flavonoids (10) in nature. Others are
amino acids (2), steroids and organic acid.
DISCUSSION
In this review, selected plants which have been
investigated for antidiabetic potentials between year 2000
and 2013 are presented. The present work and earlier
reviews on this subject show that a lot of research work
has been performed in recent times in the search for
antidiabetic agents from plants. However, not all the
listed plants from ethnobotanical surveys are fully
explored and most of the investigations have been
preliminary studies. More detailed researches are
therefore advocated in the search for more efficacious
and safer hypoglycemic agents from plants. In addition,
their long-term benefits in diabetic complications need to
be evaluated in controlled studies.
The variety of phytoconstituent classes and the wide
differences in the molecular structure of the isolated
compounds suggest the possibility of different mecha-
nisms of action in lowering blood glucose. Some have
been shown to inhibit α-amylase with others potentiating
the action or enhancing the release of insulin. Alkaloids
inhibit α-glucosidase and decrease glucose transport
through the intestinal epithelium. Polysaccharides
increase the level of serum insulin, reduce the blood
glucose level and enhance tolerance to glucose.
Flavonoids suppress the glucose level, reduce plasma
cholesterol and triglycerides significantly and increase
hepatic glucokinase activity probably by enhancing the
insulin release from pancreatic islets. Saponins stimulate
the release of insulin and block the formation of glucose
in the bloodstream (Patel et al., 2012; Bhushan et al.,
2010). The detailed investigation into the actual mecha-
nism of action of many of the plants and the isolated
compounds is however, lacking. Further investigations to
establish the actual mode of action of these plants and
the isolated compounds are needed.
Besides efficacy and mode of action, the majority of the
plants extracts and isolated compounds have not been
subjected to thorough toxicological studies in animal models
294 Afr. J. Pharm. Pharmacol.
Table 1. Medicinal plants with investigated antidiabetic potentials.
S/no.
Botanical name
Family
Significant bioactivity in relation to hypoglyceamia
1
Abelmoschus moschatus Medik
Malvaceae
The active principle of this plant, myricelin, improves insulin sensitivity in rats (Liu et al., 2007)
2
Achiliea santolina L.
Asteraceae
Exhibits hypoglycemic and antioxidant activities (Yazdanparast et al., 2007)
3
Achyrocline satureioides (Lam.) DC
Asteraceae
A new prenylated dibenzofuran, achyrofuran, derived from the plant significantly lowers blood glucose levels when administered orally at 20
mg/kg q.d (Carney et al., 2002)
4
Ajuga iva L. Schreberr (Medit)
Lamiaceae
Exhibits strong hypoglycemic effect in diabetic rats (aqueous extract at 10 mg/kg) (El Hilaly and Lyoussi, 2002)
5
Annona squamosa L.
Annonaceae
Isolated juercetin-3-O-glucoside from the leaves exhibits anti-hyperglycemic and antioxidant activities in animals (Panda and Kar, 2007)
6
Anthocleista djalonensis A. Chev (cabbage tree)
Gentianeacea
Extracts show α-amylase and in vivo hypoglycemic activity in rats (Olubomehin et al., 2013)
7
Anthocleista Schweinfurthii
Gentianeacea
Hypoglycemic (Schweinfurthiin, a new steroid and two known compounds, bauerenone and bauerenol were isolated) ( Mbouangouere et al.,
2007)
8
Anthocleista vogelii Planch
Gentianeacea
Extracts show α-amylase (Olubomehin et al., 2013)
9
Artemisia dracunculus L.(dragon herb)
Asteraceae
Hypoglycemic comparable to metformin (Ribnicky et al., 2009)
10
Averrhoa bilimbi L
Oxalidaceae
Hypoglycemic (leaf extract, 125 mg/kg, OGTT in normal and streptozotocin (STZ)-induced diabetic rats) ( Pushparaj et al., 2001)
11
Bauhinia candicans Benth
Leguminosae
hypoglycemic (20 % dried leaf infusion in alloxan-induced diabetic rats but not in normal) (Fuentes et al., 2004)
12
Biophytum sensitivum (L) DC.
Oxalidaceae
Hypoglycemic (leaf extract in alloxan-induced diabetic rabbits, OGTT) (Puri, 2001)
13
Bixa orellana L.
Bixaceae
Hypoglycemic (normal and STZ-induced diabetic dogs) (Russell et al., 2008)
14
Boerhaavia diffusa L.
Nyctaginaceae
Decreases blood glucose level and increases plasma insulin levels, antioxidant (Pari et al., 2004)
15
Brassica nigra (L) Koch
Brassicaceae
Hypoglycemic (200 mg/kg aqueous extract to diabetic animals daily once for one month) (Anand et al., 2007)
16
Butea manosperma (Lam)
Caesalpiniaceae
Anti-hyperglycemic (Somani et al., 2006)
17
Capparis spinosa L.
Capparidaceae
Hypoglycemic (aqueous extract at 20 mg/kg in STZ-diabetic rats, acute and chronic treatments; no effect on normal animals) (Eddouks et al.,
2004)
18
Carum carvi L.
Apiaceae
Potent anti-hyperglycemic (Eddouks et al., 2004)
19
Cassia auriculata L.
Caesalpinaceae
Hypoglycemic and enhances the activity of hepatic hexokinase, phosphofructokinase, suppresses glucose-6-phosphatase and fructose-l,6-
bisphosphatase in diabetic animals after 15 day treatment (400 mg/kg) (Gupta et al., 2010)
20
Cichorium intybus L.
Asteraceae
Hypoglycemic in acute and chronic studies (125 mg/kg daily for 14 days to diabetic rats attenuates serum glucose by 20%, triglycerides by
91% and total cholesterol by 16% (Pushparaj et al., 2007)
21
Clausena anisata (Willd) Benth.
Rutaceae
Hypoglycemic (800 mg/kg, p.o., normal and diabetic rats) (Ojewole, 2002)
22
Cocos nucifera Linn. (Coconut palm)
Palmae
Neutral detergent fiber from the plant tested in rats fed 5%, 15% and 30% glucose causes significant lowering in glycaemia and serum insulin
(Sindurani and Rajamohan, 2000)
23
Cogniauxia podoleana
Cucurbitaceae
Hypoglycemic and anti-hyperglycemic (Diatewa et al., 2004)
24
Commelina communis L.
Conimelinaceae
Anti-hyperglycemic, management of non-insulin-dependent diabetes (Youn et al., 2004)
25
Curcuma longa L.
Zingiberaceae
Hypoglycemic, plays a role in PPAR-gamma activation (Kuroda et al., 2005)
Osadebe et al. 295
Table 1. Cont’d.
26
Cynodon dactylon Pers. (Bermuda grass)
Poaceae
Anti-hyperglycemic (Jarald et al., 2008)
27
Eclipta alba (L) Hassk.
Asteraceae
Leaf suspension (2 and 4 g/kg, p.o.) for 60 days produces hypoglycemia and decreases the activities of glucose-6- phosphatase and fructose-
1,6-bisphosphatase, and increase the activity of liver hexokinase (Ananthi et al., 2003)
28
Enicostemma littorale Blume
Gentianaceae
Dried plant equivalent extract of 1.5 g/100 g causes hypoglycemia in diabetic rats without toxic effect (Maroo et al., 2003)
29
Eruka sativa
Brassicaceae
Hypoglycemic, antioxidant and improved lipid profile (after daily oral admin of oil of the seeds 2 weeks before or after diabetes induction with
alloxan) (El-Missiry et al., 2000)
30
Gentiana olivieri L.
Gentianaceae
Hypoglycemic, anti-hyperlipidemic (Sezik et al., 2005)
31
Ginkgo biloba L.
Ginkgoaceae
Hypoglycemic (OGTT in humans), increases pancreatic beta-cell in NIDDM (Sugiyama et al., 2004; Kudolo et al., 2001)
32
Glycyrrhiza uralensis Fish.
Papilionaceae
PPAR-gamma ligand-binding activity, decreases the blood glucose levels (Kuroda et al., 2003)
33
Gongronema latifolium Benth.
Asclepiadaceae
Antidiabetic and antioxidant (aqueous and ethanol extract of leaf, p.o.) (Ugochukwu and Babady, 2003; Ugochukwu and Babady, 2002)
34
Gymnema montanum Hook
Asclepiadaceae
Anti-peroxidative, antioxidant (Ramkumar et al., 2005)
35
Helicteres isora L., As.
Sterculiaceae
Hypoglycemic comparable with insulin and metformin, antioxidant and hypolididemic (Suthar et al., 2009)
36
Hintonia standleyana
Rubiaceae
Anti-hyperglycemic (Guerrero-Analco et al., 2005)
37
Hordeum vulgare L. (Barley)
Gramineae
Glycemic responses in healthy and Type II diabetic patients show that barley is a suitable cereal for diabetic patients (Shukla et al., 2001)
38
Ibervillea sonorae S.
Cucurbitaceae
Hypoglycemia in acute and chronic studies (Alarcon-Aguilar et al., 2005)
39
Ipomoea aquatic Forsk.
Convolvulaceae
Boiled whole extract exhibits hypoglycemic effect with optimum dose of 3.4 g/kg and optimum activity observed 2 h after admin
(Malalavidhane et al., 2003)
40
Ipomea batata Linn (Sweet potato)
Convolvulaceae
Hypoglycemia and reduction in hyperinsulinemia in rats (p.o.) in chronic studies, results comparable to troglitazone (Kusano and Abe, 2000)
41
Lepidium sativum L.
Brassicaceae
Aqueous extract (10 mg/kg/h) causes potent hypoglycemia in normal and diabetic rats (Eddouks and Maghrani, 2008)
42
Loranthus micranthus Linn
Loranthaceae
Weakly acidic fraction of methanol extract (250 and 500 mg/kg) shows activity in alloxanized rats; (Osadebe et al., 2010).
43
Morus indica. L.
Moraceae
Hypoglycemic ( Devi and Urooj, 2008)
44
Musa sapientum Kuntz (Banana)
Musaceae
Hypoglycemia in OGTT; chloroform extract of the flowers at 1.5, 0.2 and 0.25 g/kg for 30 days (p.o.) causes a decrease in blood glucose and
glycosylated haemoglobin level (Pari and Umamaheswari, 2000)
45
Ocimum sanctum Linn. (Tulasi)
Lamiaceae
Shows antidiabetic, antioxidant and other activities in diabetic rats (Vats et al., 2004)
46
Origanum vulgare L.
Lamiaceae
Aqueous extract of exhibits anti hypergly-cemic activity in STZ rats without affecting basal plasma insulin concentrations (Lemhadri et al.,
2004)
47
Phyllanthus amarus Schum. Thonn
Euphorbiaceae
Oral administration of ethanolic leaf extract (400 mg/kg) for 45 days resulted in a significant (p<0.05) decline in blood glucose and significant
recovery in body weight of diabetic mice (Shetty et al., 2012)
48
Phyllanthus niruri L.
Euphorbiaceae
Methanol extract of aerial parts shows antidiabetic activity in normal and alloxan-induced rats (Okoli et al., 2009)
49
Phyllanthus sellowianus Mull. Arg.
Euphorbiaceae
Hypoglycemic (Hnatyszyn et al., 2002)
50
Piper longum
Piperacea
The aqueous extract at a dosage of 200 mg/kg is found to possess significant antidiabetic activity (Nabi et al., 2013)
296 Afr. J. Pharm. Pharmacol.
Table 1. Cont’d.
51
Psidium guajava L.
Myrtaceae
Leaf extract inhibit the increase of plasma sugar level in alloxan- induced diabetic rats during OGTT; leaf extracts also shows significant
inhibitory effect on glucose diffusion in vitro (Mukhtar et al., 2004; Basha and Kumari, 2012)
52
Punica granatum L. (pomegranate)
Lythraceae
Hypoglycemia (aqueous-ethanolic extract of flowers in normal and hyperglycaemic rats (400 mg/kg) (Jafri et al., 2000)
53
Retama raetam (RR) (Forssk) Webb.
Papilionaceae
Aqueous extract possess significant hypoglycemic effect in normal and STZ rats (Maghrani et al., 2005)
54
Sambucus nigra L.
Adoxaceae
Insulin-releasing and insulin-like activity (Gray et al., 2000)
55
Sanguis draxonis
Apocynaceae
Increase insulin sensitivity and improve the development of insulin resistance in rats (Hou et al., 2005)
56
Sclerocarya birea (A. Rich)
Anacardiaceae
Hypoglycemic (Ojewole, 2003)
57
Scoparia dulcis L.
Scrophariaceae
Hypoglycemic, antihyperlipidemic, antidiabetic (Beh et al., 2010)
58
Spergularia purpurea
Caryophyllaceae
Hypoglycemic (aqueous extract in normal and diabetic rats at 10 mg/kg) (Jouad et al., 2000; Eddouks et al., 2003)
59
Suaeda fruticosa (SF) Euras
Chenopodiaceae
Hypoglycemic (aqueous extract in normal and diabetic rats at 192 mg/kg but no effect on plasma triglycerides in both groups (Benwahhoud et
al., 2001)
60
Syzygium alternifolium (Wt) Walp
Myrtaceae
Hypoglycemic, antihyperglycemic and antihyperlipidemic (Rao and Rao, 2001)
61
Tamarindus indica L.
Caesalpinaceae
Hypoglycemic and hypolipidemia in STZ- diabetic rats (aqueous extract of seed in a chronic study) (Maiti et al., 2005)
62
Terminalia bellirica (Gaertn)
Combretaceae
Stimulates insulin secretion. Enhances insulin action andinhibits both protein glycation and starch digestion (Kasabri et al., 2010)
63
Terminalia chebula Retz.
Combretaceae
Dose-dependent hypoglycemic, antidiabetic and renoprotective,decreases hepatic and skeletal muscle glycogen content, increases insulin
release from the pancreatic islets (Rao and Nammi, 2006)
64
Tinospora cordifolia Miers.
Menispermaceae
Hypoglycemic (aqueous root extract orally in alloxan rats, 400 mg/kg equivalent to 1 unit/kg of insulin) (Sengupta et al., 2009)
65
Urtica pilulifera L.
Urticaceae
Hypoglycemic (Kavalali et al., 2003)
66
Vernonia amygdalina Del.
Astereaceae
Extract improves biochemical and heamatological parameters in diabetic rats; combination of extract with metformin at various ratios shows
that the ratio of 1:2 (extract: metformin) causes the most significant (p<0.05) reduction in blood sugar (66.07%) compared to control (Akah et
al., 2009; Adikwu et al., 2010)
67
Withania soimifera (L) Dunal
Solanaceae
Hypoglycemic, antioxidant, diuretic and hypocholesterolemic (Adallus and Radhika, 2000)
68
Zygophyllum gaetulum Emb and Maire
Zygophyllaceae
Hypoglycemic, increases plasma insulin levels (Jaouhari et al., 2000)
let alone in clinical settings. Isolating the
compounds is a necessary step in the search for a
new hypoglycemic agent. The safety of the
isolated compounds is also of importance as it is
possible that the isolated compound could be
more toxic than when present in the plant in
association with other agents. For instance,
Galega officinals which is rich in guanidine was
traditionally used in the management of diabetes
in Europe. However, guanidine proved too toxic to
be used in clinical practice. Metformin, a
biguanide and the current drug of choice in the
management of type 2 diabetes was later deve-
loped from the guanidines (Sterne, 1969; Bailey,
1988). Those plants with promising antidiabetic
potential as well as the isolated compounds
therefore need to be subjected to detailed
toxicological evaluation.
Conclusion
The present review has indicated that there is
currently great interest in the search for anti-
diabetic agents from plants and many potential
compounds have been isolated. However, most of
the investigations have been preliminary in nature.
There is urgent need therefore to fully explore
these promising plants by carrying out further