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Frontiers in Life Science

ISSN: 2155-3769 (Print) 2155-3777 (Online) Journal homepage: http://www.tandfonline.com/loi/tfls20

Antidiabetic potential of mangrove plants: a


review
Swagat Kumar Das, Dibyajyoti Samantaray, Jayanta Kumar Patra, Luna
Samanta & Hrudayanath Thatoi
To cite this article: Swagat Kumar Das, Dibyajyoti Samantaray, Jayanta Kumar Patra, Luna
Samanta & Hrudayanath Thatoi (2016) Antidiabetic potential of mangrove plants: a review,
Frontiers in Life Science, 9:1, 75-88, DOI: 10.1080/21553769.2015.1091386
To link to this article: http://dx.doi.org/10.1080/21553769.2015.1091386

Published online: 08 Dec 2015.

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Date: 01 July 2016, At: 08:58

Frontiers in Life Science, 2016


Vol. 9, No. 1, 7588, http://dx.doi.org/10.1080/21553769.2015.1091386

Antidiabetic potential of mangrove plants: a review


Swagat Kumar Dasa , Dibyajyoti Samantaraya , Jayanta Kumar Patrab , Luna Samantac and Hrudayanath Thatoid
a Department

of Biotechnology, College of Engineering and Technology, Biju Patnaik University of Technology, Bhubaneswar 751003,
Odisha, India; b School of Biotechnology, Yeungnam University, Gyeongsan 712749, Republic of Korea; c Department of Zoology,
Ravenshaw University, Cuttack 753003, Odisha, India; d Department of Biotechnology, North Orissa University, Baripada 757003,
Odisha, India

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(Received 7 May 2015; accepted 3 September 2015 )


Diabetes mellitus is a heterogeneous group of metabolic disorders characterized by persistent hyperglycaemia and becoming
a serious threat to mankind health in all parts of the world. Production of reactive oxygen species and disturbed capacity
of antioxidant defence have been reported for enhanced production of free radicals in diabetic subjects. As oxidative stress
is found to be a central event in the development of diabetic complications, hence antioxidants may play an important
role in the improvement of diabetes and its associated complications. Currently there has been an increased interest globally to identify antioxidant compounds that are pharmacologically potent and have low or no side eects. Phytochemicals
and metabolites from mangrove plants are reported to exhibit strong antioxidant properties in terms of both enzymatic and
non-enzymatic activities. Recent researches have also revealed that a number of mangrove plants have shown antidiabetic
activities attributed to their unique metabolites such as avonoids, triterpenoids, limonoids and polysaccharides. Thus, mangrove plants can be of great use in tackling diabetic and its associated oxidative stress mediated complications. The present
review highlights a relation between oxidative stress and diabetes and the role of mangrove plants in alleviating diabetes, in
general, and oxidative stress mediated diabetic complications, in particular.
Keywords: mangroves; antidiabetic; antioxidant; oxidative stress

1. Introduction
Diabetes is a chronic metabolic disorder characterized by
absolute or relative deciencies in insulin secretion or
insulin action associated with chronic hyperglycaemia and
disturbances of carbohydrate, lipid and protein metabolism
(Bastaki 2005). There are three types of diabetes mellitus recognized by the World Health Organization (WHO)
such as (i) type 1 diabetes (insulin-dependent) (ii) type
2 diabetes (non-insulin-dependent) and (iii) gestational
diabetes. The -cells in the pancreas are the key players in glycaemic homeostasis. Glucotoxicity, lipotoxicity,
inammatory mediators and incretin were reported to modulate function and survival of -cell (Leahy et al. 2010).
Besides, oxidative stress is thought to be a major risk
factor on the onset and progression of diabetes (Rains &
Jain 2011). Both type-1 and type-2 diabetes are associated
with increased formation of free radicals and decreased
antioxidant potential (Maritim et al. 2003).
Diabetes is a common disease in the developed and
developing countries. According to a WHO report in
2011, approximately 360 million people globally suer
from diabetes. Diabetes epidemic is more pronounced in
developing countries such as India. As per reports of the
WHO, 32 million people of India had diabetes in the

*Corresponding author. Email: hnthatoi@gmail.com


2015 Taylor & Francis

year 2002 and it is expected that more people in India


will be aected by diabetes in the near future. Therefore,
management of diabetes in recent times possesses a big
challenge. Apart from insulin, several types of glucoselowering drugs (including insulin secretagogues, insulin
sensitizers, -glucosidase inhibitors, peptide analogues, dipeptidyl peptidase-4 inhibitors and glucagon like peptide1) have been developed. However, these synthetic oral
hypoglycaemic agents have characteristic proles of serious side eects, which include hypoglycaemia, weight
gain, gastrointestinal discomfort, nausea, diarrhoea, liver,
heart failure, etc. (Joshi & Joshi 2009). Thus, alternative
therapy is the need of hour.
Since centuries, many plants are considered to be a rich
source of potent antidiabetic drugs and these herbal preparations are considered to be devoid of any side eects. It
has been estimated that more than 400 plants and their
secondary metabolites such as glycosides, alkaloids, terpenoids, avonoids, carotenoids, tannins and polyphenolic
derivatives are being used for the management of diabetes
mellitus across the globe (Bailey & Day 1989). Currently
there has been an increased interest globally to identify
antioxidant compounds that are pharmacologically potent
and have low side eects for use in antidiabetic therapy.

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76

S.K. Das et al.

The mangroves (unique plant communities growing at


the interface between the land and sea in tropical and subtropical regions of the world) are capable of thriving under
stress conditions exemplied by high salinity, extreme
tides, strong winds, high temperatures and muddy anaerobic soils (Kathiresan & Ramanathan 1997). They have
highly developed morphological and physiological adaptations to the extreme conditions of their environment and
possess metabolites of unique biological activity that are
rich in medicinal potential. Traditionally, mangrove plants
are being used in folklore medicine for treatment of various ailments including diabetes (Bandaranayake 2002).
However, the antidiabetic potentials of these plants and its
correlation with antioxidant potential are yet to be established. Hence, the present review highlights a relation
between oxidative stress and diabetes and the potential

role of mangrove plants in management of diabetes and its


oxidative-stress-associated complications.
2. Pathological pathways involved in diabetes
There are four key metabolic pathways playing major
role in hyperglycaemia-induced cell damage and diabetes
associated complications such as (a) increased polyol pathway ux; (b) increased advanced glycation end product (AGE) formation; (c) activation of protein kinase
C and (d) increased hexosamine pathway ux (Robertson 2004) (Figure 1). In diabetes, cell damages are
manifested through damage to proteins, lipids and carbohydrates, while the diabetic-associated complications
include diabetic nephropathy, retinopathy, neuropathy,
etc.

Figure 1. Hyperglycaemia-induced reactive oxygen species (ROS) generation and diabetic-associated pathological complications. :
Stimulate. : Inhibit.

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77

3. Influence of oxidative stress on insulin signalling


The normal insulin signalling pathway (which is a tightly
regulated process) is found to be impaired during oxidative
stress conditions, resulting in development of insulin resistance (Evans et al. 2002). Several mechanisms have been
proposed for the causal link between oxidative stress and
impairment of insulin signalling pathways, which include
(i) activation of stress kinases, (ii) decreasing GLUT-4
gene transcription, (iii) alteration in mitochondrial activity
and (iv) free fatty acids (FFA) mediated apoptosis.
Studies have shown that oxidative stress can activate a
number of stress kinases along with activation of stress signalling pathways such as NF-. The NF- pathway is
activated by phosphorylation of a serine kinase IkB kinase
which has shown a negative eect on normal insulin signalling pathway. The activation of other stress signalling
pathways such as p38, MAPK and JNK/SAPK also interfere in the insulin signalling by dephosphorylating the IRS,
leading to deactivation of signalling cascades resulting in
insulin resistance (Baldwin 2001; Ogihara et al. 2004)
(Figure 2).
The facilitated diusion of glucose into the cell is mediated by a number of glucose transporters, of which the
GLUT1 and GLUT4 play an important role in insulin
signalling. The oxidative stress has been shown to downregulate the expression of GLUT4, which in turn decreases
Figure 3. Proposed pathway linking FFA and hyperglycaemia
in the pathogenesis of diabetes. : Stimulate. : Inhibit.

the glucose uptake, resulting in development of insulin


resistance (Bloch-Damti & Bashan 2005).
Mitochondria also play an important role in the release
of insulin from -cells in response to blood glucose levels (Rains & Jain 2011). The mitochondrial dysfunction by
oxidative stress is reported to be involved in insulin resistance and may be an underlying cause in the development
of diabetes (Szendroedi et al. 2009).
The hyperglycaemia and FFA also elevate ROS and
reactive nitrogen species production levels and activate
stress signalling pathways causing -cell dysfunction and
insulin resistance (Evans et al. 2003) (Figure 3).
4.

Figure 2. Eects of oxidative stress on the insulin signalling


pathway. : Stimulate. : Inhibit.

Antidiabetic potential of phytochemicals; a


mangrove plant perspective
Metabolites with some novel chemical structures and
diversied chemical classes have been characterized in
mangroves and mangal associates. Aliphatic alcohols,
acids, amino acids, alkaloids, carbohydrates, carotenoids,
hydrocarbons, FFA (including polyunsaturated fatty
acids), lipids, pheromones, phorbol esters, steroids, triterpenes and their glycosides, tannins, terpenes, phenolics and
related compounds are among these classes that have established pharmacological bioactivity (Bandaranayake 2002).

78

S.K. Das et al.

Table 1.

Major phytoconstituents of mangrove plants exhibiting hypoglycaemic activities.

Class of
compound

Mangrove
species

Alkaloids

Inhibit alpha-glucosidase

Glucose
transport
through the intestinal
epithelium.

Bruguiera sp.,
X. granatum

Polysaccharides

Levels of serum insulin


Blood glucose levels
Improve tolerance of glucose
Suppressed the glucose
level
Plasma cholesterol and
triglycerides signicantly
Hepatic glucokinase
activity
Stimulates the release of
insulin

S. alba

Flavonoids

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Hypoglycaemic
activity

Saponins
Phenolic
compounds

The levels of serum


insulin,
The sensitivity of tissues
to insulin action

Brugine, tropine and tropine


esters of acetic, iosbutyric, iosvaleric, propionic, n-butyric,
4-hydroxybenzoic acid, ethyl
3,4-dihydroxybenzoate
Complex polysaccharide

References
Cheng et al.
(2009)

Morada et al.
(2011)

A. ilicifolius,
Bruguiera
sp., X.
granatum

Rutin, quercetin, kaempferol,


catechin, epicatechin

Li et al. (2009)

B. gymnorrhiza,B.
sexangula
B. racemosa,
Rhizophora
sp.

-Sitosterol, -amyrin, ursolic


acid, -amyrin, stigmasterol

Nebula et al.
(2013)

Methyl 3,4,5-trihydroxy
benzoate; 3,4,5-trimethoxy
phenol 1-O--D-(6-galloyl)glucopyranoside, gallic
acid

Kabir et al.
(2013) and Li
et al. (2009)

The phytochemicals from mangrove plants with potential


hypoglycaemic activity are summarized in Table 1.
4.1.

Major
phytoconstituents

kaempferol, catechin, epicatechin and rutin) that exhibit


hypoglycaemic activities (Cheng et al. 2009; Zhu et al.
2009; Nebula et al. 2013).

Alkaloids

Alkaloids produce antihyperglycaemic action by potentiating pancreatic secretion of insulin from -cell of islets
or by enhancing transport of blood glucose to peripheral
tissue (Gulfraz et al. 2011). Alkaloids such as xylogranatinin, granatoin, acanthicifoline and trigonellin are reported
in mangrove plants such as Xylocarpus granatum and
Acanthus sp. (Li et al. 2009).
4.2. Polysaccharides
The antihyperglycaemic eect of polysaccharides is due to
the increased level of serum insulin, reduced blood glucose level and enhanced tolerance to glucose (Bhushan
et al. 2010). Morada et al. (2011) have also reported that
the hypoglycaemic property in mangrove plant Sonneratia
alba is due to the presence of a complex polysaccharide
molecule.
4.3. Flavonoids
Flavonoids might prove to be important for alternative
diabetic treatment, as it helps in preventing -cell apoptosis, promoting -cell proliferation and insulin secretion,
and enhancing insulin activity. Mangrove plants such as
Avicennia marina, X. granatum and Bruguiera sexangula
are reported to be rich in avonoids (such as quercetin,

4.4. Saponins: triterpenoid and steroidal glycosides


Triterpenoid and steroidal glycosides are collectively
referred to as saponins. These compounds are known to
possess potent hypoglycaemic activity (Rao & Gurnkel
2000). Mahera et al. (2013) reported that the presence
of stigmasterol-3-O--D-galactopyranoside and -amyrin
in mangrove plant of A. marina is responsible for its
antidiabetic activity. Similarly, bartogenic acid in another
mangrove plant Barringtonia racemosa was also found
to possess -glucosidase inhibition activity (Gowri et al.
2007). Pentacyclictriterpenoids such as oleanolic acid,
ursolic acid and lupeol found in mangrove plants such
as A. marina and Sonneratia caseolaris also exhibited
antidiabetic activities (Tiwari et al. 2010; Mahera et al.
2013).
4.5. Phenolic compounds
The phenolic compounds may exhibit their hypoglycaemic
activities by increasing the levels of serum insulin, increasing the sensitivity of tissues to insulin action, stimulating
the activity of enzymes of glucose utilization and inhibiting the activity of -amylase (Arif et al. 2014). Mangrove
plants such as B. racemosa possess phenolic compound
(such as gallic acid) that have antidiabetic activities (Kabir
et al. 2013).

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79

Figure 4. Possible role of mangrove plants in the management of diabetes and its associated oxidative-stress-mediated complications.
: Stimulate. : Inhibit.

4.6. Tannins
Tannins also play an important role in preventing diabetic
complications by reducing the formation of AGEs and
oxidative stress (Soman et al. 2013). Members of the families Avicenniaceae, Rhizophoraceae and Sonneratiaceae
are rich source of tannins (Bandaranayake 1995). Mangroves such as Xylocarpus moluccensis are reported to rich
in non-hydrolysable tannins such as procyanidindecamer
and procyanidinundecamer (Wangensteen et al. 2009).
4.7. Other compounds
Some macyrocylic polydisulde such as gymnorrhizol
from mangrove plant Bruguiera gymnorrhiza and polyacetylenes from Aegiceras corniculatum are also reported
to possess antidiabetic activity (Sun & Guo 2004; Wang
et al. 2006).
5.

Progress of antidiabetic research in mangrove


plants
Mangrove plants living in an ecological hostile condition enumerated by dierent stress conditions such as

salinity, high temperature, water logging, low oxygen and


light are reported to be rich in antioxidant compounds.
These compounds include phytochemicals such as cinnamic acids, coumarins, diterpenes, avonoids, lignans,
monoterpenes, phenylpropanoids, tannins and triterpenes
(Bandaranayake 2002; Thatoi et al. 2014). The search
for antidiabetic phytoconstituents from mangrove plants
having enriched antioxidant property has taken a pace
in recent times. Traditionally more than 100 numbers of
mangroves and mangrove-associated plant used for treatment of diabetes have been reported; however, only a
few have been evaluated and reported scientically (Bandaranayake 2002). Based upon the antidiabetic research
carried upon mangrove plants, it has been suggested that
these plants can exhibit their antidiabetic action by several
ways such as (i) insulin mimetic activity, (ii) decreasing intestinal glucose absorption, (iii) decreasing AGEs
and (iv) by exerting antioxidative eect (thereby decreasing oxidative-stress-associated diabetic complications
(Figure 4).
Some of the important mangrove plants along with
their phytoconstituents (Figure 5) and mode of antidiabetic
action are summarized in Table 2.

S.K. Das et al.

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80

Figure 5. Hypoglycaemic compounds from mangrove plants.

5.1.

A. corniculatum

A. corniculatum L. (black mangrove) belongs to the family Myrsinaceae. The dierent parts of the plant have been
traditionally used for treatment of rheumatism, arthritis,
inammation, antioxidant, free radical scavenging and

hepatoprotective action (Roome et al. 2008). Ethanolic


extract of A. corniculatum leaves regulate blood glucose
level in alloxan-induced diabetic rats at a dose of 100
mg/kg. Improvement in body weight in diabetic-induced
rat was observed along with decrease in the activities

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81

Table 2. Mangrove plants with reported antioxidant and antidiabetic activities.


Mangrove
species

Family

A. corniculatum Myrsinaceae

Phytoconstituents
Flavonoids, tannins,
saponins,

Antioxidant
activities
studied (A)
Phenolic content;
reducing ability

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polyphenols

A. ilicifolius

Acanthaceae

Flavonoids

OH radical,
DPPH, ABTS
scavenging

A. marina

Avicenniaceae

Saponins

Catalase

B. cylindrica

Rhizophoraceae avonoids, phenolic


acids, sterols/
triterpenoid,
alkaloids, tannins
anthocyanins
Lecythidaceae Flavonoids, tannins,
saponins

B. racemosa

B. gymnorrhiza Rhizosphoraeae Flavonoids, tannins, saponins,


polyphenols,
glycosides
C. decandra

C. tagal

E. agallocha

OH radical,
DPPH, ABTS
scavenging

Antidiabetic
mechanism (D)

Utilization of glucose; (A) Roome et al.


(2008);
either by direct
stimulation of glucose (D) Gurudeeban et al.
uptake or via the
(2012)
mediation of enhanced
insulin secretion;
Elevated glucose
and glycosylated
haemoglobin levels.
Regeneration of -cells of (A) Firdaus et al.
pancreas
(2013)
(D) Venkataiah et al.
(2013)
Stimulation of -cells to (A) Takemura et al.
release more insulin
(2002)
Antiglycation activity
(D) Babuselvam et al.
(2013);
Mahera et al. (2011)
Stimulation of -cells to (A) Krishnamoorthy
release more insulin
et al. (2011)
(D) Shyam and
Kadalmani (2014)

DPPH scavenging, -Glucosidase and


-amylase inhibitory
superoxide
property
scavenging,
FRAP
Presence of antidiabetic
SOD, DPPH,
principles
ABTS,
scavenging

Stimulation -cells to
release more insulin;
The increased hexokinase
activity may result in
increased glycolysis
and increased utilization
of glucose for energy
production.
Rhizosphoraeae Flavonoids, tannins,
DPPH scavenging, Inhibition against PTPase
saponins, polypheanti-lipid
enzyme activity, which
nols, glycosides,
peroxidation
plays an important
terpenoids
role in the negative
regulation of the insulin
signalling pathway;
Stimulation of glucose
uptake; -Glucosidase
inhibitory property
Euphorbiaceae Flavonoids, tanDPPH radical
Pancreatic secretion of
nins, saponins,
scavenging,
insulin; Uptake of
polyphenols phorbol
reducing
glucose.
power, H2 O2
scavenging
assay, nitric
oxide (NO)

Rhizosphoraeae Flavonoids, tannins, saponins,


polyphenols,
glycosides

DPPH radical
scavenging

References

(A) Kong et al. (2012)


(D) Gowri et al. (2007)
(A) Agoramoorthy
et al. (2008)
(D) Karimulla and
Kumar (2011)
(A) Agoramoorthy
et al. (2008)
(D) Nabeel et al.
(2010)

(A) Bunyapraphatsara
et al. (2003)
(D) Tiwari et al.
(2008); Tamrakar
et al. (2008); Lawag
et al. (2012)

(A) Patra et al. (2009)


(D) Rahman et al.
(2010); Thirumurugan et al.
(2009)

(Continued).

82

S.K. Das et al.

Table 2. Continued
Mangrove
species
H. fomes

Sterculiaceae

Phytoconstituents
Tanins, terpenoids,
avonoids

DPPH radical
scavenging
assay and 1,5lipoxygenase
inhibiting activities

Antidiabetic
mechanism (D)
Enhancement of
pancreatic secretion of
insulin;
The glucose uptake;
Inhibition in glucose
absorption in gut

References
(A) Wangensteen,
Dang et al. (2009)
(D) Ali et al. (2011)

Improved level of insulin Banerjee et al. (2008);


Agoramoorthy
secretion and its action;
et al. (2008);
Insulin mimetic activity;
Bunyapraphatsara
-Glucosidase inhibitory
et al. (2003)
(D) Lawag et al.
(2012); Nabeel et al.
(2012); Gaar et al.
(2011); Haque et al.
(2013)
R. apiculata
Rhizosphoraeae Tannin, steroids,
SOD, LPO, NO,
Improved level of insulin (A) Agoramoorthy
triterpenes, phenolic
reducing power,
et al. (2008); Sur
secretion and its action;
compounds
superoxide, OH. and Insulin mimetic activity
et al. (2015)
(D) Lakshmi et al.
-Cell protection
DPPH assays
(2006); Sur et al.
(2004), (2015);
Nabeel et al. (2012)
R. annamalayana Rhizosphoraeae Alkaloids, tanins,
DPPH scavengImproved level of insulin (A) Bunyapraphatsara
steroids
ing, anti-lipid
secretion and its action ; et al. (2003)
peroxidation
Insulin mimetic activity
(D) Ali et al. (2011);
Nabeel et al. (2012)
N. fruticans
Arecaceaea
Alkaloids, glycosides, Free radical
Utilization of glucose, (A) Prasad et al. (2013)
(D) Reza et al. (2011)
tannins, sterols
scavenging
either by direct
stimulation of glucose
uptake or via the
mediation of enhanced
insulin secretion
(A) Kaewpiboon et al.
S. caseolaris
Lythraceae
Steroids, glycosides
DPPH scavengIntestinal -glucosidase
(2012)
ing, anti-lipid
inhibitory activity;
(D) Tiwari et al.
peroxidation
Potentiation pancreatic
(2010); Rahmatullah
secretion of insulin;
et al. (2012); Hasan
Glucose uptake from
et al. (2013)
serum;
Glucose absorption
from gut.
Enhanced insulin releasing (A) Banerjee et al.
S. apetala
Lythraceae
Triterpenes, steroids, DPPH assay, NO
(2008); Vadlapudi
activity;
avonoids,
scavenging assay,
alkaloids, diterpenes
ferrous ion chelating Insulin mimetic activity;
and Naidu (2009)
Modifying glucose
assay, total
(D) Hossain et al.
utilization;
antioxidant capacity
(2013); Patra et al.
Stimulating the regenassay
(2014)
eration of islets of
langerhans in pancreas;
Enhance transport of
blood glucose to the
peripheral tissue.
S. alba
Lythraceae
Tanins, phenolic
DPPH scavengModifying glucose
(A) Bunyapraphatsara
compunds
ing, anti-lipid
utilization
et al. (2003)
peroxidation
(D) Morada et al.
(2011)
R. mucronata

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Family

Antioxidant
activities
studied (A)

Rhizosphoraeae Alkaloids, tannins,


saponins, phenolic
compunds

SOD, LPO, NO and


DPPH assays

(Continued).

Frontiers in Life Science


Table 2.

Continued

X. granatum

Meliaceae Alkaloids, steroids,


tannins, triterpenes,
Limonoids

X. moluccensis Meliaceae Alkaloids, steroids,


tannins, triterpenes,
proanthocyanidins

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83

Stimulation on -cells and


DPPH assay, NO
help in the release of
scavenging assay,
insulin;
ferrous ion chelating
Elevation in insulin
assay, total
sensitivity to glucose;
antioxidant capacity
Protein tyrosine
assay
phosphatase activity
may be helping in
insulin action
DPPH scavengInsulin mimetic or insulin
ing, anti-lipid
secretagogue activity
peroxidation
Insulin resistance
reversal activity Glucosidase inhibitory
activity

(A) Vadlapudi and


Naidu (2009)
(D) Srivastava et al.
(2011)

(A) Bunyapraphatsara
et al. (2003);
(D) Srivastava et al.
(2014)

Note: (A) References cited for antioxidant studies in mangrove plants; (D) references cited for antidiabetic studies in mangrove plants.

of glucose-6-phosphatase, fructose 1,6-bisphosphatase and


glycosylated haemoglobin. Besides, increased activity of
liver hexokinase was also observed (Gurudeeban et al.
2012).

such as stigmasterol-3-O--D-glucopyranoside may be the


hypoglycaemic components present in this plant which
could be responsible for its antiglycation activity (Mahera
et al. 2011).

5.2. Acanthus ilicifolius


A. ilicifolius (sea holly) belongs to the family of Acanthaceae. Studies have reported that oral administration of
ethanolic root extract of A. ilicifolius at a dose of 200 and
400 mg/kg body weight signicantly reduced the blood
sugar level in normal, glucose-fed hyperglycaemic and
alloxan-induced diabetic rats. Regeneration of -cells has
also been reported in the diabetic rats (Venkataiah et al.
2013). The presence of avonoids, alkaloids, terpenoids,
tannins and steroids in the root extracts of this plant may
play important role in their hypogycaemic activities.

5.4. B. racemosa
B. racemosa is an evergreen mangrove plant, belonging
to the family Lecythidaceae. The bark and leaves have
been traditionally used for anticancer, analgesic, antibacterial, anticolic and antifungal activities (Khan et al. 2001;
Thomas et al. 2002). The bark and the roots of the
plant have been reported to possess dierent compounds
such as 3,3 -dimethoxy ellagic acid, dihydromyticetin, gallic acid, bartogenic acid, stigmasterol, olean-18-en-3-O-ecoumaroylester and olean-18-en-3--O-Z-coumaroyl
esters along with germanicol, germanicone, betulinic
acid, lupeol, taraxerol, neo-clerodane type diterpenoids,
nasimalun A and nasimalun B (Sun et al. 2006; Yang et al.
2006). The hexane, ethanol, methanol extracts of seeds
of B. racemosa reported to possess -glucosidase and amylase inhibition activities (Gowri et al. 2007). Gowri
et al. (2009) also reported the presence of pentacyclic triterpenoid bartogenic acid in the methanol extracts of this
plant responsible for its antidiabetic activity.

5.3. A. marina
A. marina belongs to the family Avicenniaceae. The
ethanolic leaf extracts of A. marina has been shown to possess antihyperglycaemic activity in alloxan-induced diabetic rats. The ethanolic leaf extracts (250 and 500 mg/kg)
upon treatment on the diabetic rats for 15 days significantly reduced the blood glucose levels along with an
increase in total haemoglobin (Hb), total protein and serum
insulin level. The A. marina leaf extract can reduce the
level of serum urea that conrms the capacity to protect
vital tissues, for example, kidney, liver and pancreas. It also
improved the biochemical parameters such as serum phosphorous, albumin and globulin. The possible mechanism
underlying the antihyperglycaemic action of A. marina
is attributed to stimulation of surviving -cells releasing
more insulin (Babuselvam et al. 2013). Methanolic extract
of pnuematophores (aerial roots) of A. marina exhibits
antihyperglycaemic eect, which might be due to inhibition of AGEs. Studies have reported that triterpenoids

5.5. B. gymnorrhiza
The genus Bruguiera has six species and belongs to
the family Rhizophoraceae. The ethanolic bark extract
of B. gymnorrhiza displayed antihyperglycaemic eect
in streptozotocin (STZ)-induced diabetic rats. The potent
antidiabetic compounds of this plant include phytoconstituents such as bruguierol, -sitosterol, -amyrin, amyrin, lupeol, oleanolic acid, ursolic acid, taraxerol, gymnorhizol and ellagic acid. The treatment with ethanolic
bark extracts (400 mg/kg) for 21 days reported signicant
reduction in blood glucose level in the STZ-induced dia-

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betic rats, which was comparable to that of a standard drug


glibenclamide (0.5 mg/kg). Further, a decreased level of
total cholesterol, triglycerides, very low density lipoprotein, low density lipoprotein along with increased high
density lipoprotein level in the diabetic rats was observed
(Karimulla & Kumar 2011).
5.6. Ceriops sp.
The genus of Ceriops has two species namely Ceriops
decandra, Ceriops tagal and belongs to the family Rhizosphoraceae. The ethanolic leaf extract of C. decandra (120 mg/kg) showed a signicant serum-glucoselowering property in alloxan-induced diabetic mice upon
oral administration, which was comparable to those of
glibenclamide (0.1 mg/kg bw) (Nabeel et al. 2010). The
treatment of diabetic rats with ethanolic leaf extracts
resulted in an increase in insulin secretion, body weight,
Hb levels and decrease in HbA1c levels. It was also
found to regulate the key enzymes involved in the glucose
metabolism such as hexokinase, glucose-6-phosphatase
and fructose 1,6-bisphosphatase. The activity of both
glucose-6-phosphatase and fructose 1,6-bisphosphatase
was found to be near-normal levels upon administration
of ethanolic leaf extracts to the diabetic rat. Increased hexokinase enzyme activity was also reported in the diabetic
rats. The possible mechanism underlying the antihyperglycaemic action of C. decandra may be due to the stimulation
of surviving -cells to release more insulin (Nabeel et al.
2010). Tiwari et al. (2008) reported that the ethanolic
leaf extract of C. tagal improved the glucose tolerance
of the normoglycaemic rats post sucrose load and also
lowered the blood glucose levels in STZ-induced diabetic rats after oral administration at a 250 mg/kg dose.
The hexane sub-fraction of ethanolic leaf extract of C.
tagal (100 mg/kg bw) was found to be most eective
for the antihyperglycaemic activity in normal healthy rats
post sucrose load, which was comparable to the eect
of metformin. The compounds isolated from the hexane
fraction of the C. tagal also showed signicant inhibition against PTPase enzyme activity, which help in insulin
action (Tiwari et al. 2008). Similarly n-hexane soluble fraction of ethanolic leaf extracts of C. tagal was reported
to stimulate the glucose uptake in L6 muscle cells in a
dose-dependent manner, which is comparable to the standard drug metformin (Tamrakar et al. 2008). In another
study, the hydroalcoholic bark extracts of C. tagal showed
antihyperglycaemic activity, which was attributed to its
-glucosiadase inhibition potential (Lawag et al. 2012).
5.7. Excoecaria agallocha
E. agallocha, a mangrove species, belongs to the genus
Excoecaria of the family Euphorbiaceae. Rahman et al.
(2010) showed that the methanol stem extract of E. agallocha reduces the serum glucose levels at doses of 200

and 400 mg/kg, which was signicantly lower than the


level observed with glibenclamide (10 mg/kg bw). E. agallocha has been reported to contain b-amyrin acetate, which
may be responsible for its antidiabetic activity (Tian et al.
2008). Thirumurugan et al. (2009) also reported that the
ethanolic leaf extracts of E. agallocha showed signicant hypoglycaemic activity. The antidiabetic potential is
attributed to the presence of bioactive principles such as
avonoids, triterpenoids, alkaloids and phenolics.
5.8. Heritiera fomes
H. fomes belongs to the family Sterculiaceae. The crude
methanol extract of H. fomes bark showed dose-dependent
reductions in concentrations of serum glucose in mice. At
60 min following glucose administration, the bark extract
signicantly lowered serum glucose levels by 49.2% at a
dose of 250 mg extract/kg body weight in comparison to
43.5% by glibenclamide. Further it was investigated and
reported that the crude methanolic extract of the bark has a
long-term action in its glucose-lowering eect and is better
than glibenclamide (Ali et al. 2011).
5.9.

Rhizophora sp.

The mangrove genus Rhizophora belongs to the family Rhizosphoraceae. Of the ten species of genus Rhizophora, the antidiabetic activity has been reported in three
species: Rhizophora apiculata, Rhizophora annamalayana
and Rhizophora mucronata. The ethanolic root extracts of
R. apiculata showed promising antihyperglycaemic activity at 250 mg/kg in experimental rats. The chloroform and
aqueous sub-fractions of ethanolic root extract of the plant
is rich in phytochemicals responsible antihyperglycaemic
activity. Further purication led to the isolation of seven
pure compounds: lupeol, oleanolic acid, -sitosterol,
palmitic acid, -sitosterol--D-glucoside, inositol and
pinitol. Among these compounds, inositol and pinitol
showed promising activity in the STZ model at 100
mg/kg dose level (Lakshmi et al. 2006). The ethanolic leaf extracts of R. apiculata showed hypoglycaemic
and antihyperglycaemic eect in normal, glucose-fed and
STZ diabetic rats (Sur et al. 2004, 2015). The hypoglycaemic action of R. apiculata is attributed to the presence of avonoids along with other bioactive compounds.
The antidiabetic properties of the hydro-methanolic leaf
extracts of this plant can be attributed to its radical scavenging and -cell protection properties.
Nabeel et al. (2012) have reported the antidiabetic
potential of three mangrove plants: R. mucronata, R. apiculata and R. annamalayana. Oral administration of 60
mg/kg aqueous extract of leaf modulated the parameters
such as blood glucose, plasma insulin, body weight, total
haemoglobin, glycosylated haemoglobin, liver glycogen,
plasma and tissue lipids, cholesterol, triglycerides, FFA
and phospholipids to normal levels in the alloxan-induced

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Frontiers in Life Science


diabetic rats. The antidiabetic activity of R. apiculata
was more pronounced than that of the other mangrove
extracts. The presence of an insulin-like protein in the
mangrove extracts was detected by sodium dodecyl sulfate
polyacrylamide gel electrophoresis analysis and conrmed
through enzyme linked immunosorbent assay. The antidiabetic activity of the mangrove plants may be due to the
improved level of insulin secretion and its action (Nabeel
et al. 2012). Gaar et al. (2011) investigated the antidiabetic eect of R. mucronata, which is due to its capacity
to inhibit carbohydrate digestion and absorption. Haque
et al. (2013) reported that the aqueous bark extracts of
R. mucronata possess signicant hypoglycaemic and antihyperglycaemic activities. The bark extracts of this plant
showed dose-dependent antidiabetic eects, which signicantly suppressed postprandial hyperglycaemia. The glucose absorption inhibition could have been the possible
mechanism behind its hypoglycaemic eect. In another
study, the hydroalcoholic bark extracts of R. mucronata
showed antihyperglycaemic activity, which was attributed
to its -glucosiadase inhibition potential (Lawag et al.
2012).
5.10. Nypa fruticans
N. fruticans (Arecaceae) is a mangrove palm well known
for its traditional uses by the local practitioners against
dierent ailments in southern regions of Bangladesh. The
methanolic leaf and stem extracts of this plant (500 mg/kg)
has been shown to exert signicant antihyperglycaemic
eect in diabetic mice (Reza et al. 2011).
5.11.

Sonneratia sp.

The mangrove genus Sonneratia belongs to the family


Lythraceae. Of the twenty identied species of genus
Sonneratia, the antidiabetic activity has been reported in
three species such as S. alba, Sonneratia apetala and S.
caseolaris. Fruits of S. caseolaris have many therapeutic
applications in folklore medicine (Bandaranayake 2002).
Compounds such as oleanolic acid, -sistosterol--Dglucopyranoside and luteolin isolated from the methanolic
extract of its fruits have shown inhibition of -glucosidase
enzyme in a dose-dependent manner (Tiwari et al. 2010).
Further, the methanolic fruit extracts of this plant signicantly reduced the serum glucose concentrations in
glucose-loaded mice in a dose-dependent manner (Rahmatullah et al. 2012; Hasan et al. 2013). The antihyperglycaemic activities of this plant may be due to a number
of factors such as decreased intestinal glucose absorption, increase in pancreatic secretions, glucose uptake,
insulin secretion and better glyceamic control. Morada
et al. (2011) reported the antidiabetic potential of methanolic leaf extracts of S. alba using in vivo mice model.
The tremendous blood-glucose-attenuating activity of the
extract was attributed to complex polysaccharide molecule

85

obtained from S. alba leaf extracts. Signicant reduction


in sugar level was observed during the rst 6 (19.2%) and
12 h (66.9%) after the administration of the extracts to the
diabetic mice. Similarly, the antihyperglycaemic activity of
seeds and pericarps of S. apetala fruits were reported in
STZ-induced diabetic mice (Hossain et al. 2013). The antihyperglycaemic activity of this plant may be due to insulin
mimetic activity, better glucose utilization, regeneration of
islets of langerhans in pancreas and enhanced transport of
blood glucose to the peripheral tissue.

5.12. Xylocarpus sp.


The genus Xylocarpus belongs to the family Meliaceae
and consists of three species such as X. granatum, Xylocarpus mekongensis and X. moluccensis. The antidiabetic
activities have been reported in X. granatum and X. moluccensis. X. granatum (which is commonly known as cannon
ball tree and found in the coastal region of India, Australia, South East Asia and East Africa) was reported
to possess antidiabetic activity (Srivastava et al. 2011).
The ethanolic extract of epicarp of X. granatum showed
improvement of oral glucose tolerance post sucrose load in
STZ-induced diabetic rats. It also showed blood-glucoselowering eect and improvement in insulin resistance. The
common biochemical markers of diabetes (that is, glucose6-phosphatase, phosphorfructokinase, phosphoenolpyruvate carboxy kinase, pyruvate kinase, lactate dehydrogenase and glycogen phosphorylase of liver and kidney in
STZ-treated rats) were also found towards normalization
after the oral treatment of the extracts at 250 mg/kg dose
for three weeks. The antidiabetic eects may be due to
increase insulin release and inhibition of -glucosidase
enzymes.
The ethyl acetate soluble fraction of epicarp of
X. moluccensis (EAXm) showed both antidiabetic and
antidyslipidemic eects in diabetic-induced rats. The
treatment with EAXm led to a signicant fall in the
elevated blood glucose level in the STZ-induced rats,
which was found to be comparable to standard drug metformin. The extracts signicantly increased both serum
insulin and HDL-C levels. The extract also displayed
enormous ability to improve the liver and renal functions as evident by decline AST, ALT, urea, uric acid
and creatinine levels in the serum. Treatment with EAXm
also restored the altered activities of few key regulatory enzymes involved in carbohydrate metabolism such
as glucokinase, phospho-fructokinase, pyruvate kinase,
glucose-6-phosphatase, fructose-1,6-bisphosphatase and
glycogen phosphorylase in liver, muscle and renal tissues of STZ-induced diabetic rats. The EAXm also displayed an in increase glucose uptake and inhibition of
alpha-glucosidase enzyme as evident by various in vitro
studies. The mechanism of antihyperglycaemic activity of
this plant extract may be due to insulin mimetic, insulin

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secretagogue and insulin resistance reversal activity (Srivastava et al. 2014).


6. Epilogue
The modulation of cellular signal transduction pathways
by naturally occurring phytochemicals has recently been
extended to elucidate the molecular basis of diseases, in
general, and diabetes, in particular. Many of the agents
which are a mainstay of pharmacotherapy in diabetes have
been shown to have antioxidant properties in addition to
their primary pharmacological actions. Therefore, strategies to block the formation of reactive radicals or scavenging the reactive free radical may provide a targeted and
casual approach for the treatment of diabetes. Discussions
vide supra clearly points towards the therapeutic potentials
of diabetes by mangrove plant extracts as they have shown
substantial hypoglycaemic and insulin mimetic potential
with pronounced antioxidant activity. The mangrove plants
survive in an ecologically hostile condition where no other
plants could survive; therefore they are supposed to be
rich in antioxidant compounds which can be exploited
therapeutically. This review has covered only 18 potential mangrove plants that could be used in the treatment
of diabetes. However, some of the other mangrove plants
that have not yet been fully explored may have therapeutic
applications in diabetes. The development of new antidiabetic moieties from bioactive compounds is necessary
in order to nd more eective and less toxic antidiabetic
drugs. Therefore, extensive study on the potential of mangrove plants with isolated active compounds that have
shown antidiabetic activity should go through additional
in vitro and in vivo animal testing followed by toxicity and
clinical tests. This may provide a promising compound to
be optimized and suitable for application in the production
of new antidiabetic compounds.
Disclosure statement
The authors declare that they have no conicts of interest to
disclose.

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