Plant Extracts are the Potential Inhibitors of α-Amylase: A Review
Syed Bilal Shah1*, Lubna Sartaj2,
Syed Izhar Ali Shah3, Muhammad Tahir Khan4
1State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong
University, China
2Department of Biochemistry, Abdul Wali
Khan University Mardan, Pakistan
3Department of Microbiology and Biotechnology, Abasyn University
Peshawar, Pakistan
4Department of Bioinformatics,
Capital University of Science and Technology,
Pakistan
*Corresponding
author: Syed
Bilal Shah, State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong
University, China. Tel: +8613122176291; Email:
bilalshah@sjtu.edu.cn
Received Date: 25
August, 2018; Accepted Date: 14 August,
2018; Published Date: 20 September,
2018
Citation: Shah SB,
Sartaj L, Shah SIA, Khan MT (2018) Plant Extracts are the Potential Inhibitors
of α-Amylase: A Review. Arch Bioequiv Availab: ABA-102. DOI:10.29011/ABA-102.000002
1. Abstract
Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia with disturbances of carbohydrate, lipid and protein metabolism resulting from defects in insulin secretion, insulin action or both. Among the various therapeutic approaches to treat diabetes, postprandial hyperglycemia reduction is at most importance. This approach is used to prevent absorption of glucose by the inhibition of enzymes which hydrolyze carbohydrates, such as alpha-amylase. The α-amylase is one of the main products of secretion of the salivary glands and pancreas, which plays a role in the digestion of starch and glycogen and can be found in microorganisms, plants and higher organisms. α-amylase enzyme catalyzing the initial step in the hydrolysis of starch to the oligosaccharide mixture consisting of maltose, malt triose 6-8 and oligosaccharides containing glucose units both α-1,4 and α-1,6 linkages branched. Here in the present work a review was carried to collectively highlight all those potent alpha-amylase inhibitors whose sources are plants. These inhibitors possess antioxidant and are the considered strong tools in future treatments of diabetes mellitus as well free from side effects.
2. Keywords: Carbohydrates; Diabetes Mellitus; Hyperglycemia
3. Introduction
Diabetes mellitus is a group of metabolic
diseases considered by hyperglycemia resulting from failures in insulin
secretion, insulin function or both. It is
characterized by hyperglycemia and accompanied by various chronic vascular complications
[1,2]. An estimated 171 million people worldwide
have diabetes,
which may probably double in 2030 and
about 3.2 million deaths each year are attributable to complications of
diabetes; six deaths every minute [3,4].
Oligosaccharides and disaccharides are
decomposed into monosaccharides by Glycosidase and α-amylase.
Starch is primarily broken down to oligosaccharides owing to the hydrolytic
activity of these enzymes [5]. Like other
nutrients, carbohydrates are mostly digested in the small intestine; however, it
is the salivary amylase that sets out almost 5% of the initial breakdown of
carbohydrates in the mouth. Due to acidic environment amylase activity is
destroyed and hence digestion of carbohydrates is not ensured in the stomach [6]. Conversely, there is a whole different nature of
small intestine where bicarbonates released from the pancreas is basic enough
to neutralize the low pH and optimize the conditions for pancreatic amylase to
properly accomplish the breakdown of carbohydrates into oligosaccharides [7]. The glucosidase enzymes (maltase, lactase and
sucrase) secreted by intestinal mucosa complete the breakdown of oligosaccharides
into monosaccharide units which are only then absorbed by the body and transported
to the liver through the portal vein. Body utilizes these monosaccharides as
one of the most direct sources of energy for various life process while those unused
are immediately stored in the liver as glycogen or in the form of fat (triglycerides)
in adipose tissue, plasma and liver [8]. Those carbohydrates
which are indigestible in the small intestine are subjected to bacterial
fermentation in the colon to produce methane, carbon dioxide and short chain fatty
acids. Salivary α-amylase, because of its substantial
utility in the oral cavity, has been exploited as a target for designing
structural based compounds that could preclude the formation of plaque and further
succession of dental caries. Ethno pharmacologically tackled bioassay directed isolation
and have granted an advantage in the identification of possible inhibitors of α-amylase from plant resources [9]. The procedure of finding concentrations of α-amylase inhibitor depends on the extent of α-amylase activity resulting from iodine staining power
in the presence/absence of an inhibitor for the enzyme action on soluble starch
or using an alkaline reactive brown whose reduction products are determined
photo metrically as reported by Bernfeld [10,11].
This review emphasizes on α-amylase inhibitory
activity of those plants and derived compounds so far recently reported.
4. Potent
Inhibitors of α-Amylase from Different Plants Extracts
Herbivorous insects use a plug of
extracellular enzymes to digest their food. One of these is α-amylase, which binds to 1,4glycoside
and slash in starch, glycogen, oligosaccharides
and polysaccharides. Several functional
proteins such as lectin, knottin-like, cereal type, Kunitz, c-purothionin-like,
and thaumatin, which is often found in
the seeds of legumes and graminaceous plants,
has been reported to inhibit α-amylase
of the insect midgut, thus blocking the main source of
energy for growth and development of insects [12].
Joining these ICA and amylase protein forms a stable enzyme-inhibitor complex. This leads to excessive larvae
digestive glands secrete digestive enzymes and answers larvae cause sanorexia, hypogenesis,
and even death [12,13]. AAIS protein
are major, however, are non-competitive inhibitors of
the insect midgut and α-amylase have their own particular kinetic properties regarding inhibitory activity,
pH optimum, thermal stability, and optimal incubation
time. Further practical application of natural biogenic protein ICA still needs
more research before may be used as tools for insect pest control.
Several authors have reviewed the possibility
of medicinal plants as inhibitors of α-amylase. It has been reported that around 800different
plant species exhibit anti-diabetic properties relevant to the
treatment of type 2diabetes. A wide range of principles derived
from plants belonging to the compounds, mainly glycosides, alkaloids, hypoglycans, galactomannan gum,
polysaccharides, steroids, peptidoglycan, guanidine, glycol
peptides and terpenoids, have shown biological
activity against hyperglycemia [14]. A list of plants reported to have significant inhibitory activity
against α-amylase
enzyme is shown in (Table 1). L.
Syzygium cumini
L. (syn: Eugenia jambolana Lam) and Psidium guajava L. are extensively used traditional system of
medicine for the treatment of diabetes in India. Aqueous
extracts of seeds and P.S. cuminigua java leaves both demonstrate dose-dependent
inhibitory effect on α-amylase activity [15]. Extract
of S. cumini seeds also drastically diminish blood glucose point in
diabetic rats [14,16]. It
was confirmed that the extracts of ethyl acetate, methanol, and hexane from two varieties of Amaranthus caudatus L.
Seeds (White and Red Victor Oscar. Oil) showed inhibitory activity of α-amylase
(above 80 % inhibition rate) by 0.251mg/ mL. Extracts buffered various
plant species namely Desert date L., Camellia sinensis L.
Del., Galega officinalis L., Holarrhena floribunda
(Don) Durand and Schinz, Khaya
senegalensis (Desr.) A. Juss., Melissa officinalis
L., Mitragyna inermis (Willd) O. Ktze., Rosmarinus officinalis L., Securidaca long epedunculata Fresen., Tamarindus
indica L., Taraxacum officinale web. Wiggex., Vaccinium myrtillus L. and were selected for α-amylase activity and showed momentous inhibitory
activity (above 45% inhibition rate of 0.2g /ml) [17]. The methanol extracts of 41 plants used in traditional
medicine in Mongolia
have been tested for α-amylase
inhibitory properties and significant inhibition of the enzyme was
demonstrated by Rhodiola
rosea L., Ribesand vacciniumulig in osumpullchelum Turcz L;
geranium
extracts pretense L, Leontopodium ochroleucum Beauv., Paeonia
anomala L., and Penta phylloides fruticosa L. Schwarz illustrate α-amylase
inhibitory activity greater than 30% [18].
Loizzo, et al. [19] examined
extracts of methanol, hexane and chloroform
from nine Lebanon recommended for diabetes traditional medicinal plants [19]. Ayurveda, the traditional system of herbal medicine practiced in India for over
thousands of years have reports of anti-diabetic plants with no known side effects
apparent [20,21]. Chloroform
extracts six plants Azadirach taindica A.
Linumusita
tissimum L., Jussnamely, S. cumini,
Tenuflorum ocimum L., Curry tree (L.) Spreng and traditionally used din Ayurveda with Bougain villea spectabilis Willd, used as a plant of
hypoglycemia in the West Indies and Asia were selected for inhibitory activity of
α-amylase Significant inhibition with extracts from O. tenuflorum [20]. Six more Indian medicinal
plants were tested for their effect on α-amylase
activity between them, Mangifera indica L., Embelia ribes Burm.,
Phyllanthus
mader as patensis Linn. Punica granatum L. and showed interesting inhibitory activity of α-amylase [22]. The enzyme α-amylase inhibitor(α-AI), which inhibits
the animal saliva and pancreatic α-amylase,
has been identified and isolated from various species of plants
[23]. Among these plants,
seeds of Phaseolus vulgaris L.
containing protein inhibitor sand α-amylase inhibitor-1
iso-form α-AI have been isolated
and characterized. A α-AI
common bean-1 has been reported to have relatively great
potential as an anti-obesity and anti-diabetes remedy [23] extensive.
Diabetes was multi factorial in origin and
therapeutic approach to treat diabetes was to delay glucose absorption through
the inhibition of enzymes α-amylase. Brown
extracts of rice was also evaluated for its α-amylase
inhibitory potential. Inhibitors α-amylase
digestion and absorption of carbohydrates glucose lag, and therefore could be
beneficial against the onset of type 2 diabetes.
The inhibitory activity of α -amylase shown in Figure 1.
As the results, in free phenolic compounds, extracts of red rice have the
highest inhibition activity (78.56%), while extracts from black rice have lower
activity inhibition (53.63%) and inhibition activity of extracts of black rice
was (68.16%). Similarly, in consolidated form, inhibition activity was greater
in extracts of red rice (48.67%) and lowest in extracts of white rice (30.60%).
Free forms of phenolic compounds always have the highest inhibiting activity of
phenolic compounds bound form three types of rice.
Inhibition activities of α-amylase free and bound phenolics. In some previous
studies, the presence of α-amylase inhibitors
have also been reported in grains [25], wheat [21], Linumusita tissimum L., sorghum [23], maize (Blanco-Labra and [21],
peanuts [19], Linumusita tissimum L., and calluses [26],
In the present study, we detected a high percentage of inhibition in extracts
of red rice (78.56%). These results indicate that phenol compounds in rice
mainly existed in the free form rather than in bound form. There is a positive
relationship between total phenolic content, antioxidant capacity and
inhibition activity of α-amylase. It also
confirms that the red brown rice not only consumed as functional foods, but
also use as pharmaceutical drugs. As the mechanism and metabolism of brown rice
extract involved in this inhibitory activity corresponding to type 2 diabetes α- amylase effect is unclear and work.
On bioavailability of phenolic compounds
has been limited, it is vital to do more research on the metabolic pathway and
functional mechanism of extract of brown rice on type 2 diabetes [30].
Alpha amylase enzyme plays an important role in start breakdown complex
carbohydrate into simple molecules. Intonation of α-amylase activity using affects
carbohydrates as an energy source and this intonation stronger. Most significantly is decomposition of complex carbohydrates. Most studies have focused on phenolic compounds amylase antibodies. The
proposed inhibitory capacity of flavonoids action mechanism correlates inhibition
potency of these compounds with the number of hydroxyl groups in the B ring of the
flavonoid skeleton with the formation of hydrogen bounds between the hydroxyl
groups of the ligands polyphenol and the catalytic residues of the binding site
of the enzyme. The high inhibitory capacity observed in flavonols and in their
groups. It is [31] suggested that the interaction between tannins, quinic acid as
galloylated, α-amylase
and human also correlates with free OH groups in the tannin,
which are capable of participating in hydrogen bonding. However,
in this review may notice that the tannins are not always an
effective inhibitor of α-amylase. This compound showed 100% inhibition in 24 hours and 50% inhibition
at same next time. The similar process was conducted to estimate
this activity in both studies. However, the extract
concentration and incubation time for tested enzyme were different for both [28]. The study showed distinction
in the concentration of the test compound and incubation
time of the enzyme [16], the
changes showed in the result clearly. Inhibitions of 85%
and 50% rosmarinic acid and 23% and 55% for daidzein in tests using starch and nitrophenyl-maltopentao side ρ-α-D- (PNPG) as substrate
respectively [27]. Comparing study of α-amylase inhibitory
activity observe significant difference in the percentage inhibition for the
same compound. This is due to a number of valuable test
methods available for amylase activity [32].
5. Conclusions
and Future Developments
Alpha-amylase,
salivary or pancreatic enzyme plays an important role in early
break down complex carbohydrate into simple molecules. Modulation
of α-amylase activity using
affects carbohydrates as an energy source and this modulation is stronger.
Most significantly is decomposition of complex carbohydrates.
Therefore, some changes in the trials reported
by investigators could express different results for the inhibitory activity of
α-amylase. As the intake of phenolic compounds is associated with many
beneficial effects, it is also necessary to consider the dosage for humans,
because it is possible to reduce the activity of α-amylase by eating food or rich
medicinal herbs in polyphenols with strong activity α-amylase,
if one takes into consideration that this source of polyphenols
have different types of these compounds in varying concentration. Therefore, the available evidence is most
needed about the safety of using α-amylase
inhibitors natural. From the above study it is concluded that,
there is a need for new agents, therapeutic
strategies or design of functional foods that could act in the physiological
regulation of the absorption of sugar, sugar levels in
the blood and prevention of oral diseases. For the
future a standardized protocol for potential inhibitors perhaps should be
developed in order to minimize the differences between the results obtained.
Considering the above discussed literature and potent antidiabetic
potentialities, ethno-medicinal plants may play a very important role in the
modern system of medicine and these efforts may provide treatment to everyone
and focus on the role of traditional novel medicine plants that have
anti-diabetic abilities.
6. Funding
The author(s) received no financial support for the
review, authorship, and/or publication of this review article.
Figure:1 Alpha-amylase
% inhibition activities in various types of rice.
Plant |
Part used |
Type of extract |
Activity (% inhibition) (concentration)(mg/ml) |
Control |
References |
Acanthaceae Andrographis paniculate Nees |
Leaf and aerial parts |
Ethanol |
52.5 (50.9) 54.8 (11.3) |
Acarbose with 50.1% of maxim inhibition at 10mg/mL |
[24] |
Actinidiaceae Actinidia deliciosa |
Leaf |
Methanol 90% |
50 (0.0429) |
Voglibose with 50% of inhibition at 0.0466mg/mL |
[25] |
Balanitaceae Balanitesa egyptiaca L |
Bark |
Aqueous buffered |
45-75 (200) |
Acarbose inhibition higher than 75% at 200mg/mL |
[17] |
Coniferae Ginkgo biloba L |
Leaf |
Ethanol |
70 (50) |
Non-treated enzyme |
[26] |
Ericaceae Vaccinium myrtillus L. |
Leaf |
Aqueous buffered |
> 75 (200) |
Acarbose, inhibition higher than 75% at 200mg/mL |
[17] |
Geraniaceae Geranium pratense L. |
Aerial part |
Methanol |
43.9 (0.3mg/mL) |
Acarbose with 79.6% of inhibition at 0.1mg/mL |
[18] |
Fabaceae Cajanus cajan L. |
Seed |
Aqueous buffered |
100 (2mg protein) |
Non-treated enzyme |
[27] |
Malvaceae Hibiscus sabdariffa Linn. |
Flower |
Methanol 50% |
100 (10mL/g fr. wt.) |
Non-treated enzyme |
[28] |
Myrsinaceae Embelia ribes Burm. f. |
Seed |
Ethanol |
59.3 |
Phaseolus vulgaris with 59.4% of inhibition at 0.0125mg/mL |
[22] |
Paeoniaceae Paeonia anomala L. |
Root |
Methanol |
33.1 (0.3mg/mL) |
Acarbose with 79.6% of inhibition at 0.1mg/mL |
[18] |
Pinaceae Cedrus libani A. Rich |
Essential oils from cones
|
Aqueous buffered |
31 (1) |
Acarbose with 50 % of at inhibition 1.22mg/mL |
[19] |
Polygalaceae Securidaca longepidunculata Fresen |
Root |
Aqueous buffered |
20-45 (200mg/mL) |
Acarbose with inhibition higher than 75% at 200mg/mL |
[17] |
Punicaceae Punica granatum L. |
Fruit rind |
Ethanol |
68.2 (1) |
Phaseolus vulgaris with 59.4% of inhibition at 0.0125mg/mL |
[22] |
Rosaceae Pentaphylloides fruticosa (L.) |
Leaf and branch |
Methanol |
31.2 (0.3mg/mL) |
Acarbose with 79.6% of inhibition at 0.1mg/mL |
[18] |
Rubiaceae Mitragyna inermis (Wild) |
Leaf |
Aqueous buffered |
75 |
Acarbose with inhibition higher than 75% at 200mg/mL |
[17] |
Rutaceae Murraya koenigii L. |
Leaf |
Chloroform |
56.64 |
Acarbose with 50 % of at inhibition 1.22mg/mL |
[20] |
Saxifragaceae Bergenia ciliata, Haw.
|
Rhizome |
Methanol 50% |
93.5 (150) |
Non-treated enzyme |
[29] |
Theaceae Camellia sinensis L. |
Leaf |
Aqueous buffered |
45-75 (200) |
Acarbose with inhibition higher than 75% at 200mg/mL |
[17] |
Table 1: Plants with α-amylase inhibitory activity.