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Diabetes mellitus is a chronic metabolic disease. Oxidative stress plays a major part in the pathogenesis of diabetes. Supplementation with antioxidants and the medicinal plants which possess antioxidants activity have been reported their hypoglycemic activity. The antioxidants are used to treat and reduce the complication of diabetes mellitus. The diet supplementations of antioxidants vitamins are beneficial in the treatment of diabetes. This review article was summarizing the role of antioxidants in diabetes mellitus.
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Vol 11, Issue 2, 2018
Online - 2455-3891
Print - 0974-2441
1Department of Biochemistry, Research and Development Centre, Bharathiar University, Coimbatore, Tamil Nadu, India. 2Department of
Biochemistry, Madha Dental College and Hospital, Kundrathur, Chennai, Tamil Nadu, India. 3Department of Pharmacology, Meenakshi
Ammal Dental College and Hospital Maduravoyal, Chennai, Tamil Nadu, India. 4Department of Biochemistry, Rajas Dental College and
Hospital, Kavalkinaru Junction, Tirunelveli, Tamil Nadu, India. Email:
Received: 23 October 2017, Revised and Accepted: 15 November 2017
Diabetes mellitus is a chronic metabolic disease. Oxidative stress plays a major part in the pathogenesis of diabetes. Supplementation with antioxidants
and the medicinal plants which possess antioxidants activity have been reported their hypoglycemic activity. The antioxidants are used to treat and
reduce the complication of diabetes mellitus. The diet supplementations of antioxidants vitamins are beneficial in the treatment of diabetes. This
review article was summarizing the role of antioxidants in diabetes mellitus.
Keywords: Antioxidants, Diabetes mellitus, Oxidative stress, Medicinal plants.
Diabetes mellitus is an insistent metabolic disorder characterized
by an aberrantly upraised level of blood glucose due to the deficit in
insulin secretion by the β-cells of the pancreas and/or resistance
toward the exploit of hormone insulin associated with disturbances
in the carbohydrates, lipids, and proteins metabolism which leads to
long-term complications. International Diabetes Federation conferring
371 million people affected by diabetes and the number likely to
elevate 552 million by 2030. Based on the previous experimental and
clinical studies recommend that oxidative stress plays a main role in the
pathogenesis of diabetes. This article reviews the role of antioxidants
in diabetes [1].
Free radicals are a molecule with one or more single pair of the electron
that can quickly react with the constituents such as proteins, nucleic
acid, and lipids. The reactive molecule comprises the reactive oxygen
species (ROS) and reactive nitrogen species was derived from oxygen
and nitrogen, respectively. These reactive particles are generated in
cellular membrane, mitochondria, nucleus, lysosome, peroxisome,
endoplasmic reticulum, and cytoplasm. The enhanced generation of the
reactive species associated with hyperglycemia [2].
Oxidative stress plays a key role in the development of wide range of
diseases including cancer, cardiovascular disease, diabetes, aging, liver,
and lung diseases. Oxidative stress due to an imbalance between radical
engendering and radical scavenging systems. Previous experimental
studies have been reported overproduction of free radicals and defect
of antioxidants protection involved pathogenesis of diabetes [3]. The
mechanism behind the prooxidant-antioxidant imbalance in diabetes
mellitus is auto-oxidation of glucose, increased the formation of
advanced glycation end products (AGEs), polyol pathway, hexosamine
pathway, and mitochondrial respiratory chain. The enzymatic source of
free radical generation includes nitric oxide synthase, NADPH oxidase,
and xanthine oxidase [4].
In most of the animal research, the chemicals or drug is used for the
induction of diabetes. The well-known chemical compound used in
diabetic research is alloxan; it is a toxic compound which destroys the
beta-cells of the pancreas. In previous research, alloxan used to induce
type 1 diabetes in animals such as rat, mice, and rabbits. Nowadays,
instead of alloxan, streptozotocin used for induction of Types 1 and 2
diabetes due to their toxicity and instability [5].
Streptozotocin is a glucosamine nitrosourea compound has a chemical
name of 2-deoxy-2(methyl nitrosamino)carbonyl)amino)-D-glucose
derived from a fermentation broth of Streptomyces achromogenes. It
is toxic glucose analog generally used to induce experimental diabetes.
Rakieten et al. [6] were the first to demonstrate that STZ-induced
diabetes in an animal model. Based on the previous experimental
model, it is frequently used single intravenous dose between 40 and
60 mg/kg of body weight [7].
The streptozotocin enters into the beta-cells of pancreas through
glucose transporter 2 (GLUT 2). The mechanism behind the
streptozotocin action in the beta-cell is DNA alkylation due to the
presence of methyl nitrosourea moiety. Transfer of methyl group
from streptozotocin to DNA cause damage, resulting in the formation
of DNA fragmentation [8]. However, the synergistic action of nitric
oxide and ROS it may contribute beta-cell destruction. The damage to
DNA activates poly ribosylation; it leads to depletion of NAD and ATP
eventually may lead to beta-cell death [9].
Antioxidants are substances able to slow or inhibit the oxidation of
other molecules. Recently, the medicinal field focused the antioxidants
therapy in the management of numerous diseases, especially diabetes.
Preceding experimental studies and clinical trials have suggested
the efficacy of antioxidants in preventing diabetes complication. The
therapeutic strategy uses the antioxidants as a substrate, combined
drug, synthetic antioxidants, and drug with antioxidants activity. In
general, the medicinal plants with antioxidants activity are considered
for the treatment of diabetes mellitus [10].
The antioxidants therapy defends the beta-cell against oxidative stress-
induced apoptosis and preserves the function of the beta-cell. Data
from earlier studies show the antioxidants diminish diabetic-related
complication and recover insulin sensitivity. Epidemiological studies
© 2018 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.
org/licenses/by/4. 0/) DOI:
Review Article
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Rajendiran et al.
revealed a strong association between the dietary antioxidants intake
and protection against diabetes.
Vitamin E
It is naturally occurring lipophilic antioxidant exists as tocopherol
and tocotrienol. It defends the cell against oxidative damage. It is
believed Vitamin E playing a key role in controlling hyperglycemia,
and the combined antioxidants therapy also considered for control and
prevention of diabetic complication. The studies in an animal model
have shown supplementation of Vitamin E decreases the hepatic lipid
peroxide level in streptozotocin-induced diabetes [11]. However, the
increased level of lipid peroxide due to change of antioxidant status in
the diabetic rat.
Dietary vitamin and administration of Vitamin E positively associated
with glucose concentration. The level of glucose significantly decreased
and the OGGT improved in diabetic condition by supplementation of
Vitamin E [12]. During diabetic condition, the antioxidant enzymes SOD,
CAT, and GPX decreased. However, the oral administration of Vitamin E
(440 mg/kg of body weight, once a week for 30 days) significantly
increased SOD and GSH-Px activity and decreased the hydroperoxide
level due to an improvement of glycemia [13].
During diabetic condition, the excess glucose attached to hemoglobin to
produce glycosylated hemoglobin. It is an important marker for diabetes
which is prevented Vitamin E treated rat in diabetic condition [14].
Vitamin E has been shown to controls hyperglycemia and lowering
the HbA1c by inhibiting the sequence of oxidative stress in diabetic
rats [15]. The mechanism by which antioxidants reduced the glucose
levels not yet clear, but the plasma glucose level decreased by increasing
the glucose metabolism in peripheral tissues [16]. Supplementation
of Vitamin E (1800IU/day) showed that the serum level of Vitamin E
increases in Type 1 diabetes and control rats, whereas the retinal blood
flow significantly increased and elevated baseline creatinine clearance
normalized, but the HbA1C level not affected in the same experiment. It is
achieved by unchanged glycemic control and normalization of DAG/PKC
pathway through activation of DAG kinase in diabetic patients [17].
In synergy with β-carotene and Vitamin C, it is reduced the risk of
diabetes and cancer. The antioxidant property of Vitamin E associated
with the prevention of hyperglycemia and minimizes the macrovascular
and microvascular complications in individuals with diabetes [18].
Vitamin C
It is powerful antioxidants scavenging free radicals in aqueous
compartment. It is essential to convert Vitamin E free radicals to
Vitamin E, as a cofactor required for hydroxylation reaction in human.
The most important function of Vitamin C is key chain-breaking
antioxidants in the aqueous phase. It provides stability to the cell
The research conducted by Yazd Diabetes Research Center, Iran, has
been reported that totally 84 diabetic patients received 500 mg or
1000 mg of ascorbic acid daily for 6 weeks. The daily consumption of
1000 mg of Vitamin C may be beneficial in reducing blood glucose level
and lipids, whereas 500 mg not significantly made any change during
the parameter studied [19].
Eriksson and Kohvakka studied the effect of Vitamin C supplementation
(2 g/day for 90 days) in 56 diabetic patients; the result has shown the
high-dose supplementation reduced the level of fasting blood glucose,
HbA1c and improve glycemic control [20]. Frequent intake of Vitamin C
dietary source was found to decrease the risk of Type 2 diabetes in a
population-based study [21].
Administration of Vitamin C and E (100 mg/kg of body weight of rat)
significantly reduced the blood glucose level [22]. However, lowered
level of ascorbic acid and SOD observed in the diabetic subject when
compared to the non-diabetic person [23]. The increased level of
Vitamin C in diabetes may due to increased utilization in trapping the
oxyradicals. Some of the studies have been reported that diabetes may
result in decreased plasma Vitamin C and E due to increased oxidative
stress [24].
The mechanism behind the treatment of diabetes is not clear. However,
it diminishes the microalbuminuria, erythrocyte sorbitol levels and
plays a chief role in ameliorating insulin resistance of diabetic patients
due to its antioxidant function [25,26].
Alpha-lipoic acid
A potent antioxidant, it is also known as 1, 2-dithiolane-3-pentanoic
acid or thioctic acid.
Alpha-lipoic acid fights cellular injuries triggered by free radicals, those
unstable, highly reactive molecules that are derivatives of both normal
and frazzled cell activity. It has a capability to restore endogenous
antioxidants such as glutathione, Vitamin E, and Vitamin C. It is effective
in many pathological conditions such as cardiovascular disease,
diabetes mellitus, and liver disease [27,28].
Alpha-lipoic acid has been reported to progress glucose metabolism
in Type 2 diabetes mellitus patient by directly activate lipid, tyrosine,
and serine/threonine kinases in target cells, due to these mechanisms
which stimulate glucose uptake and glycogenesis. In vitro studies have
reported that the alpha-lipoic acid increases the translocation of GLUT1
and GLUT4 to the plasmatic membrane of adipocytes and skeletal
muscle. It is related to an improved activity of proteins of insulin
signaling pathway [29].
Budin et al. [30] had reported that the intake of ALA reduced the
glucose level and total cholesterol in STZ-induced diabetes in rats. It
also regenerates the other antioxidants such as Vitamin C, Vitamin E,
and SOD in diabetic condition. The same results have been previously
reported in experimental animals [31].
Jacob et al. have been reported that the administration of 500 mg of ALA
in Type 2 diabetes patients for 10 days shown a significant increase of
insulin-stimulated glucose disposal (30%) and no changes observed in
fasting plasma glucose level or insulin. In the clinical study, 20 patients
received 500 mg, it able to improve insulin resistance in NIDDM [32].
Same results were obtained by chronic administration (100 mg/kg) of
antioxidant in type 2 diabetes mellitus [33].
In another study, the oral supplementation ALA (600 mg twice daily for
4 weeks) treatment which increases the plasma insulin sensitivity [34].
According to Packer et al., ALA is capable to scavenge ROS produced
during the lipid peroxidation and guards the cell structure against
damage. The continued supplementations of the LA in diabetic rats
were associated with diminution of both hyperglycemia and diabetic
nephropathy [35].
It is important trace element, naturally present in many foods. It exists
in organic and inorganic forms. Selenomethionine and selenocysteine
belong to organic form; selenate and selenite are inorganic forms.
Mostly the inorganic selenite presents in the soil. Selenium plays a major
role in thyroid hormone metabolism and immune functions. Based on
previous experimental and clinical studies, selenium focused on the
prevention of many diseases due to their antioxidant activity [36].
Previously, selenium was found as a toxic component due to Se
poisoning in animals and humans, thereafter, it was recognized as
essential element since selenium deficiency considered a major
problem in animal and human [37]. The supplementation of selenium
with low doses has a beneficial effect on glucose metabolism, which
mimics insulin-like actions in the animal experimental model. While
the mechanism behind the mimicking insulin is not clear, however, the
previous report showed that Se activates the key protein responsible
for insulin signal cascade [38].
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The inorganic selenium compound sodium selenate and sodium
selenite involved in insulin signaling cascade by activation of kinases. In
animal experimental studies shown selenate stimulate glucose uptake
and involved phosphorylation of insulin receptor and insulin receptor
substrate 1 [39,40] and the oral administration or intraperitoneal
injection of daily doses of selenate for 3-8 weeks in streptozotocin-
induced diabetic rat, the result shown that the raised glucose level to
be reduced [41,42].
In another study stated the above-mentioned insulin-like activity of
selenium due to increased glucose tolerance and alteration in the
activity of gluconeogenic and glycolytic maker enzyme. In the same
way, selenomethionine also studied their antioxidant activity in a
diabetic animal, supplementation of selenomethionine, Vitamin E
plus selenomethionine in type I diabetic rat for 24 weeks effectively
decreased the glucose and glycosylated hemoglobin level [43].
Numerous studies have reported that Vitamin E, C, and alpha-lipoic
acid and selenium frequently used antioxidants in the management
of diabetes. Nowadays, the antioxidants-based formulation developed
for the treatment of various diseases. Table 1 summarizes antioxidants
efficacy of vitamins in diabetes.
Medicinal plants are tremendous in the treatment of numerous
diseases due to their antioxidant activity. All parts of medicinal plants
are effective in the treatment of disease and help to discover new kind
of drug. The plants contribute a potential source of hypoglycemic drugs
due to their phytoconstituents [44].
The active constituents responsible for hypoglycemic activity may
include polysaccharides, sterol, triterpenoid, alkaloids, flavonoids, fat,
coumarins, phenolics, and peptides. It stimulates the beta-cell to restore
the function of pancreatic tissue [45]. The insulin secretion in beta-cell
increased and the uptake of glucose increased by adipose tissue and
muscle in plant treated rat, at same the time the absorption of glucose
decreased and hepatic glucose production decreased by inhibiting the
enzymes [46]. Some of the antidiabetic plants possess antioxidants
activity include Nerium oleander Linn. [47], Annona squamosa [48],
Cynodon dactylon [49], Padina boergesenii [50], and Tectona grandis
Linn. [51]. Table 2 summarizes antidiabetic plants which possess
antioxidants activity. Medicinal plants have a long history in the
treatment of diseases majorly in diabetes; therefore, it focused mainly
due to its curative property with fewer side effects.
Table 1: Antioxidant efficacy of vitamins and supplements in diabetes
Antioxidants Dosage Diabetogen Efficacy Reference
Vitamin E 500 mg/kg on the day 1, 4,
7, 11, 14.21, 24, 27
Streptozotocin (single dose
60 mg/kg body weight)
Lowered lipid peroxide level
in the liver of the diabetic rat
Seven et al. (2004)
Vitamin C 500 mg twice a day Type 1 and 2 diabetic
Supplementation of Vitamin C
with metformin reduces FBS,
PMBG and improves HbA1c.
Ganesh et al. (2011)
Vitamin E + Vitamin C Vitamin C 60 mg daily and
Vitamin E 200 mg twice a
week for 5 weeks
STZ (single dose 75 mg/Kg
body weight)
Reduced hepatic lipid peroxide,
normalized Vitamin C, and
raised Vitamin E above the
normal level.
Madhu et al. (2000)
Alpha-lipoic acid 300 mg daily Type 2 diabetic patients Decreased FBS and IR Hasti et al. (2011)
(sodium selenite)
0.5 µg/day STZ (55 mg/kg body weight) Selenium reduced oxidative
stress associated diabetes
Mukherjee et al. (1998)
Plants name Extract Dose Efficacy Reference
Allium sativum L. Ethanolic
extract of the
500 mg/kg body
weight of rat
decreased the blood
sugar level
Shakya et al. (2010)
Aloe vera (L.) Aqueous extract
of leaves
500 mg/kg body
weight of mice
Hypoglycemic and
Sharma et al. (2013)
Table 2: Shows the antidiabetic plants which possess antioxidants activity
Asian J Pharm Clin Res, Vol 11, Issue 2, 2018, 48-53
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Plants name Extract Dose Efficacy Reference
Syzygium cumini Walp. (Eugenia jambolana) Seed powder 500 and 1000 mg/kg
body weight of rat
Sridhar et al. (2005)
Mimosa pudica Thottal vadi
(Leaves and
100 and 200 mg/kg
body weight of rat
Vishwanathan et al. (2013)
Momordica charantia Alcoholic
extract of bitter
0.5-1.5 g/kg body
weight of rabbits.
Vangoori et al. (2013)
Psidium guajava Ethanolic
extract of leaf
250 mg/kg of body
weight of rat
Mukhtar et al. (2004)
Mangifera indica Ethanolic
extract of seed
300 mg/kg of body
weight of rat
Gupta and Gupta (2011)
Andrographis paniculata Ethanolic
extract. (Aerial
0.1, 0.2, and 0.4 g/body
weight of rat.
Hypoglycemic and
Zhang et al. (2000)
Table 2: (Continued)
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Among the antioxidants, the diet-derived antioxidants are important
in the prevention and management of various diseases. Over the past
decades, antioxidant-based experimental research emerged in the
production of a new drug. However, many drugs are in clinical trials
which possess antioxidants activity.
Based on the review, supplementation of antioxidants such as
Vitamin E, C, alpha-lipoic acid, and selenium shows their hypoglycemic
and hepatoprotective effect, but some of the studies have been reported
that vitamin supplementation does not affect glucose level. In diabetic
condition, the low level of vitamin reported in the previous study. The
mechanism behind the antioxidant is undefined, most of the study
reported it prevent and minimize the complication of diabetes.
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... Naturally derived antidiabetic drugs are currently becoming popular because of high financial burdens and side effects that are coupled with allopathic therapy strategies for the treatment of diabetes. Antioxidants are substances that inhibit oxidation and are considered to have medicinal value in treatment of several diseases like diabetes (Arguelles et al., 2017;Rajendiran et al., 2018). Diabetes treatment using antioxidants (such as thioctic acid, tocopherol, and vitamin C) protects beta-cells against oxidative stress-induced apoptosis and prevents complications caused by the disease. ...
... Studies using streptozotocin-induced diabetic rats showed that antioxidant therapy (diet supplementation) using tocopherol and vitamin C lowers the concentration of lipid peroxide and significantly increases superoxide dismutase (SOD) activity improving the health condition of the animal (Seven et al., 2004). In addition, vitamin C therapy in diabetic rats lowers the erythrocyte sorbitol levels and helps in improving the insulin resistance of the animal (Rajendiran et al., 2018). These findings suggest that dietary supplementation of antioxidants may reduce the complication of diabetes and are beneficial for diabetes treatment (Seven et al., 2004;Rajendiran et al., 2018). ...
... In addition, vitamin C therapy in diabetic rats lowers the erythrocyte sorbitol levels and helps in improving the insulin resistance of the animal (Rajendiran et al., 2018). These findings suggest that dietary supplementation of antioxidants may reduce the complication of diabetes and are beneficial for diabetes treatment (Seven et al., 2004;Rajendiran et al., 2018). ...
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Seaweeds are considered natural sources of chemical compounds with notable potent antioxidant and antidiabetic activities. The study aims to know the total polyphenolic content (TPC) and assess the antioxidant and antidiabetic activities of Sargassum polycystum for potential pharmacological use. The seaweed has a TPC of 1.149 ± 0.22 mg GAE/g. Antioxidant activity of S. polycystum is characterized by having potent scavenging activity against ABTS+ radical and high copper reduction capacity with IC50 value of 49.50 μg GAE/ml and 20.40 μg GAE/ml, respectively, more effective than ascorbic acid (control). Assessment of the antidiabetic properties of S. polycystum was done in vitro via α-amylase and α-glucosidase inhibition assay. Results of the analysis proved that S. polycystum has potent α-amylase (IC50 of 0.264 μg/ml) and α- glucosidase (IC50 of 120 μg/ml) inhibition activities in collation to that of acarbose (antidiabetic drug) with IC50 values of 4.81μg/ml and 6771 μg/ml, respectively. This study is a pioneering research investigation in the Philippines describing the bioactive properties of S. polycystum as renewable source of bioactive substances for inhibition of important carbohydrate degrading enzymes.
... The long term use of these synthetic α-glucosidase inhibitors has been reported to cause multiple detrimental effects including liver disorders, abdominal pain, hepatic injury, abdominal fullness, flatulence, and diarrhoea [5]. According to the researchers, antioxidants play an important role in preventing complications of diabetes and recovering insulin sensitivity by protecting the β-cell against apoptosis that occurred during oxidative stress [6]. Therefore, the antioxidant and α-glucosidase inhibitor-rich traditional medicinal plant-based products may be an excellent option for treating or controlling diabetes without any adverse side effects. ...
... α-glucosidase inhibitors retard the action of α-glucosidase on the hydrolysis of carbohydrates, thereby delaying the carbohydrate digestion from the small intestine at postprandial conditions as a result decrease the glucose level in type-2 diabetes patients which occurs due to the impairment of insulin sensitivity and pancreatic β-cell. Similarly, antioxidants have been reported to play a crucial role in restoring insulin sensitivity by protecting the β-cell against apoptosis that occurs during oxidative stress [1,6]. Hence, all the hit compounds were considered for an in silico molecular docking to determine their mechanism of action as α-glucosidase inhibitors. ...
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The fruit of Phaleria macrocarpa have been traditionally used as an antidiabetic remedy in Malaysia and neighbouring countries. Despite its potential for diabetes treatment, no scientific study has ever been conducted to predict the inhibitor interaction of the protein α-glucosidase identified in an extract prepared with a non-conventional extraction technique. Hence, the major aim of this research was to evaluate the in vitro antioxidant, the α-glucosidase inhibitors, and the molecular dynamic simulations of the α-glucosidase inhibitors identified by Quadrupole Time-of-Flight Liquid Chromatography Mass Spectrometry (Q-ToF-LCMS) analysis. Initially, dry fruit were processed using non-conventional and conventional extraction methods to obtain subcritical carbon dioxide extracts (SCE-1 and SCE-2) and heating under reflux extract (HRE), respectively. Subsequently, all extracts were evaluated for their in vitro antioxidative and α-glucosidase inhibitory potentials. Subsequently, the most bioactive extract (SCE-2) was subjected to Q-ToF-LCMS analysis to confirm the presence of α-glucosidase inhibitors, which were then analysed through molecular dynamic simulations and network pharmacology approaches to confirm their possible mechanism of action. The highest inhibitory effects of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and α-glucosidase on SCE-2 was found as 75.36 ± 0.82% and 81.79 ± 0.82%, respectively, compared to the SCE-1 and HRE samples. The Q-ToF-LCMS analysis tentatively identified 14 potent α-glucosidase inhibitors. Finally, five identified compounds, viz., lupenone, swertianolin, m-coumaric acid, pantothenic acid, and 8-C-glucopyranosyleriodictylol displayed significant stability, compactness, stronger protein-ligand interaction up to 100 ns further confirming their potential as α-glucosidase inhibitors. Consequently, it was concluded that the SCE-2 possesses a strong α-glucosidase inhibitory effect due to the presence of these compounds. The findings of this study might prove useful to develop these compounds as alternative safe α-glucosidase inhibitors to manage diabetes more effectively.
... Antioxidants showed promise in avoiding diabetic complications, according to these studies. Antioxidants are used as supplements, in combination with other drugs, as synthetic antioxidants, and as active therapeutic agents (Rajendiran et al., 2018). Diabetes mellitus therapy often involves the use of medicinal herbs with antioxidant activity (Kelly, 1998). ...
... Antioxidants reduce diabetes complications and restore insulin sensitivity, according to previous research. Epidemiological research has shown that a diet high in antioxidants reduces the risk of diabetes (Rajendiran et al., 2018). Therefore, findings from this research showed how seed supplementation was able to boost the flies antioxidant enzymes production. ...
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Earlier studies have reported that tamarind seed, which is an underused part of the tamarind fruit tree, may be able to help treat diabetes. The seed has rich nutrient content, but its consumption is limited due to its hard structure and the presence of anti‐nutrient factors. To get over this constraint, the seed is usually pre‐treated to minimize anti‐nutrients and improve palatability. This study was carried out to determine the effect of fermentation on the anti‐diabetic properties of tamarind seeds in sucrose‐induced diabetic‐like phenotypes in Drosophila melanogaster. Flies were divided into six (6) groups of 40 flies each; group I (control) was fed a basal diet, group II fed 30% sucrose only, and groups III‐VI were fed 30% sucrose each and treated with varying concentrations of the sample (raw and fermented) for 14 days. The survival rate and behavioral studies were assessed after treatment. Furthermore, the homogenates were assayed for inhibitory activities of carbohydrate metabolizing enzymes (α‐amylase and α‐glucosidase). Total thiol content and antioxidant enzyme activities like catalase, superoxide dismutase, and glutathione‐S‐transferase were carried out. The results showed a reduction in survival rate and locomotor performance in the flies fed with high sucrose diet (HSD). Elevated levels of α‐amylase, α‐glucosidase, ROS, and significantly reduced antioxidant enzyme activities were also observed in flies fed with HSD. These alterations were ameliorated in flies treated with dietary inclusions of both raw and fermented seeds; while no significant difference was observed between the ameliorative effects of raw and fermented samples against elevated α‐amylase and α‐glucosidase activities, however, fermented samples exhibited significantly higher antioxidant properties. Conclusively, this study revealed that the anti‐diabetic properties of tamarind seeds were conserved by fermentation with improved antioxidant properties in the Drosophila model of diabetes‐like phenotype.
... An additional advantage of using plant raw materials is that they are rich in polyphenolic compounds and exhibit potent antioxidant activity [4]. Antioxidant activity protects β cells from oxidative stress-induced apoptosis and preserves their function [5]. ...
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Five varieties of Actinidia leaves (Geneva, Jumbo, Ken’s Red, Kijivska Hibridna, and Sentyabraskaya) were analyzed. The profiles of active compounds were determined, namely quercetin, rutin, epicatechin, chlorogenic acid, and kaempferol, in the raw material. Suspecting that the raw material might prove important in the treatment of diabetes, the authors assessed the antioxidant activity and the ability to inhibit enzymes responsible for the development of diabetes (α-glucosidase and α-amylase). As a result of the conducted analysis, the Ken’s Red variety was indicated as having the highest biological activity (DPPH IC50 = 0.332 ± 0.048; FRAP IC0.5 = 0.064 ± 0.005; α-glucosidase inhibition IC50 = 0.098 ± 0.007; α-amylase inhibition IC50 = 0.083 ± 0.004). In order to increase the efficiency of the extraction of active compounds from Ken’s Red variety leaves, cyclodextrins (α-CD, β-CD, and γ-CD) were used as extraction process enhancers. The obtained results showed a significant increase in the contents of extracted active compounds. In addition, the type of CD used enhanced the extraction of selected compounds (quercetin, kaempferol, rutin, chlorogenic acid, and epicatechin. This study shows that the application of cyclodextrin-based extraction significantly improved the leaf activity of the Ken’s Red variety (DPPH IC50 = 0.160 ± 0.019; FRAP IC0.5 = 0.008 ± 0.001; α-glucosidase inhibition IC50 = 0.040 ± 0.002; α-amylase inhibition IC50 = 0.012 ± 0.003).
... The vitamins including C, D, E, B 12 , B 6, and folic acid [8] which are found in abundance in the MedDiet also support the oxidant defense system and overall health. Vitamins E, C, and β-carotene are well-known antioxidants present in the MedDiet which have been shown to be significant antioxidants with health benefits [24][25][26][27]. Circulating vitamin D is increased in the MedDiet [28]. ...
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The Mediterranean diet is characterized by an increased consumption of fruits, vegetables, grains, and fish. Olive oil and herbs and spices are also essential components of this food regimen. Such a diet is associated with a reduced risk of cardiovascular disease, overall mortality, reduced incidence of Parkinson’s and Alzheimer’s diseases, and reduced cognitive impairment. Some of the bioactive components that exert beneficial effects are ω-3 fatty acids, polyphenols, and alkaloids that have neuroprotective, anti-inflammatory, antioxidant, antimicrobial, and gluco-regulating properties. These beneficial effects contribute to improved health including organ health and cognitive function. While the number of such bioactive plant constituents is numerous, this review will examine the role of specific bioactives and vitamins and assess the molecular mechanisms including the antioxidant and anti-inflammatory beneficial effects of the bioactive components in the Mediterranean diet.
... Diabetes mellitus (DM) is a group of heterogeneous metabolic disorders characterized by increment levels of blood glucose that resulting from impairments secretion, and action of insulin, or both [1]. Type 2 diabetes mellitus is the most common and widespread type of diabetes in the worldwide. ...
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Diabetes mellitus is a group of metabolic disorders characterized by the presence of hyperglycemia in the absence of treatment. The heterogeneous aetio-pathology includes a defect in insulin secretion, action, or both. Periostin is a matricellular protein that is a member of the fasciclin (fasc) family and has structural similarities with the transforming growth factor—β inducible protein and insect axon guidance fasciclin1. The objective of this study was to comparison of the serum level of periostin in patients with T2DM and control to assess if there is an association of periostin with diabetic control in diabetic patients and to study the effect of age and duration of disease on the serum level of periostin. In the present study, included 175 participants categorized into two main categories; 89 patients with type 2 diabetes mellitus as cases, the serum to measure fasting blood glucose, lipid profile, and periostin.
... Oxidative stress plays a crucial role in the progression of diabetes and its complications. Many medicinal plants possess potent antioxidant activities, have been reported to have the correlation with their hypoglycemic activities and are considered to be used for the therapeutic treatment of diabetic complications (Rajendiran et al., 2018). Many published studies have suggested that the antioxidant activity of plant extracts is related to their antidiabetic activities and antiglycation activity. ...
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Diabetes mellitus is the most common non-infective disease characterized by hyperglycemia (high level of blood glucose). Formation of advanced glycation end products (AGEs) in long termed-hyperglycemia and oxidative stress are the key factors to accelerate diabetic complications. To screen potential candidates for treating diabetes, total phenolic content, total flavonoid content, antioxidant activity from crude extracts of some Thai edible plants were primarily assessed, and the inhibiting potential of diabetes and its complications provided from some of these plants were evaluated in terms of their inhibitory activities of α-amylase, α-glycosidase, and AGEs formation. The highest amounts of phenolic and flavonoid compounds were found in the ethanolic extract of Caesalpinia mimosoides (S20, 12.63 ± 1.70 mg GAE/g DW) and Glochidion hirsutum (S8, 3.02 ± 0.25 mg CE/g DW), respectively. The highest antioxidant activity was found in Schinus terebinthifolius Raddi (S26, 217.94 ± 32.30 μg AAE/g DW) whereas the highest inhibitory activities of α-amylase and α-glycosidase were obtained from Basella alba L. (S11, IC50 = 0.21 ± 0.01 mg/ml) and S. terebinthifolius (S26, IC50 = 0.05 ± 0.02 mg/ml) respectively. The inhibitory effects of AGEs formation were studied in vitro using two model systems: BSA-glucose and BSA-methylglycoxal (MGO). The extracts of Glochidion hirsutum (Roxb.) Voigt (S8, IC50 = 0.20 ± 0.01 mg/ml) and Polygonum odoratum Lour. (S13, IC50 = 0.03 ± 0.01 mg/ml) exhibited the inhibitory activity of AGEs formation derived from glucose (BSA-glucose system) stronger than aminoguanidine (AG) (0.26 ± 0.00 mg/ml), which is a common AGEs formation inhibitory drug. By BSA-MGO assay, the inhibition of some selected extracts in this study (G. hirsutum, G. sphaerogynum, and S. terebinthifolius with IC50 = 0.11 ± 0.01, 0.11 ± 0.01, and 0.10 ± 0.00 mg/ml, respectively) were slightly less efficient than AG (the IC50 = 0.06 ± 0.00 mg/ml). These results indicated that some selected Thai edible plants in this present study provided potential applications towards the prevention of diabetes and their complications via the inhibitory of α-amylase, α-glycosidase, AGEs formation, and oxidative stress. This fundamental information would be important for alternative drug discovery and nutritional recommendations for diabetic patients.
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Background: Diabetes mellitus is a chronic disease with an increasing prevalence worldwide and characterized by an increase in oxidative stress and inflammation. The most important factor that is responsible for oxidative stress and production of reactive oxygen species (ROS) is hyperglycemia. The major targets of ROS are proteins. The most common and widely used biomarker of severe oxidative protein damage is protein carbonyl content. The study was designed to assess the serum level of protein carbonyl as a marker of protein oxidation in patients with type 2 diabetes mellitus and to evaluate the effect of age, body weight, waist circumference, diabetic control and disease duration on the level of protein carbonyl. Subjects and Methods: This is a case-control study that included 91 patients with type 2 diabetes mellitus Eighty-five non-diabetic apparently healthy subjects matched for both age and sex with cases were enrolled as controls. Fasting blood samples were collected after an overnight fasting to measure protein carbonyl, fasting blood sugar, lipid profile, and glycated hemoglobin. Results: The level of serum protein carbonyl was significantly higher in diabetic patients than in controls and positively correlated with glycated hemoglobin, age of participant and disease duration as well as with body mass index and waist circumference. Conclusion: Diabetes mellitus is associated with an increase in protein oxidation in term of increase in the level of serum protein carbonyl with significant association in those who had poor glycemic control, obesity, higher age, and prolonged disease duration suggest that the carbonyl content of protein may be useful in evaluating the disease progression. Significant positive correlation of protein carbonyl together with waist circumference suggest that individual with central obesity are more susceptible to protein oxidation.
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Background: Diabetes mellitus is one of the most common metabolic disturbances associated with carbohydrates, lipids, proteins, and relative or absolute insulin depletion. Various long-term complications of diabetes develop due to chronic hyperglycemia and insulin resistance. Chronic kidney disease (CKD) and diabetes mellitus (DM) are major public health problems worldwide. Turmeric is one of the medicinal herbs studied for antioxidant, antibacterial, and antifungal effects. Curcumin has been established to be defensive against nephropathy. Objective: The purpose of this study was to assess turmeric's effect on different kidney function parameters in patients with type 2 diabetes mellitus (T2DM). Materials and Methods: Two hundred patients with T2DM were selected in randomized control trial, of which 100 subjects were enrolled in the study group, were given 500 mg of raw turmeric powder in capsule form daily along with their antidiabetic drug medication (Metformin) for 3 months period while 100 subjects on medication of antidiabetic drug (Metformin) were selected as a control group. Serum levels of urea, creatinine, total protein, albumin, and globulin were measured at baseline and after 3 months intervention period. Results: Showed a significant reduction in serum creatinine and significant improvement in total proteins and albumins in the study group by the end of 3 months of turmeric supplementation. Conclusion: Supplementation of turmeric leads to improved plasma proteins and decreased serum urea and creatinine levels in T2DM patients and could be useful in the improvement of kidney function in T2DM.
Plants and their bioactive compounds are used in medicinal practices since ancient times. The Himalayan region possesses a large number of medicinal plants, which have been used to prevent and cure several human diseases. Diabetes is a major public health problem, which affects millions of people worldwide. Due to its complexity and impact on whole body hemodynamics, there is no cure for any type of diabetes, and most of the available drugs only help manage the symptoms to a certain extent. Moreover, the development of drug with lesser or no side effects is still a challenge to the medical system. Plant products and their derived active compounds can be possible alternatives for the treatment of diabetes without much adverse effects. Therefore, analysis on such plants and their metabolites has become important. However, routine efforts to identify the plant-based active compounds are not sufficient and there is a need for more rigorous scientific validation to ensure their efficacy, safety, and consistency. In addition, analysis of the chemical structure of a bioactive compound and its relationship with biological activity (structure–activity relationship or SAR) is crucial as it allows the modification of the bioactive compound by changing its chemical structure; this can be considered as a powerful tool in the discovery of drugs, which are very selective and have less side effects. Although several plant-based medicines are being used traditionally for treating diabetes and have been scientifically validated, their mechanism of action is yet to be defined. Here, we review several plant species of the Himalayan region that can be effectively used to treat diabetes and their bioactive compounds having antidiabetic properties and discuss their structure–activity relationship and probable molecular mechanism underlying these properties.
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Objective: Extraction and evaluation of the antidiabetic activity of extracts from stem and roots of Nerium oleander (Apocynaceae) Linn.Methods: Stem and roots of N. oleander were collected, dried and extracted by using well-established methods for alkaloids, flavonoids, steroids and crude extracts in polar and non-polar solvents. Evaluation of their antidiabetic activity was done with salivary alpha-amylase and starch as a substrate using chromogenic DNSA (2,4-Di nitro Salicylic Acid) method and Starch-iodine method. All experiments were performed in 3 different sets each in triplicates. The data are expressed as mean±SEM (standard error of the mean).Results: The highest inhibition for stem was found in its free flavonoid extract at the concentration of 1.5 mg/ml, with percent inhibition 48.35±1.36 % and an IC50 value of 1.774 g/ml while in case of root, highest inhibition was obtained at 1.5 mg/ml of pet ether extract, with % inhibition 52±0.40 % and IC50 value 1.583 g/ml and at 1.5 mg/ml of methanol extract, with % inhibition 42.12±1.12 % and an IC50 value 1.729 g/ml. 8 (5 of stem and 3 of root) out of 14 tested extracts have shown good inhibitory potential. Extracts of the stem were found to be more potent than root extracts.Conclusion: Though stem extracts were found to be a more potent hypoglycemic agent than root extracts, however, extracts of both parts have good antidiabetic potential and both might be fruitful in managing the postprandial hyperglycemia.
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Objective: Antidiabetic activity of various solvent extracts of leaves of Cynodon dactylon in alloxan induced diabetic rats was assessed. Methods: After 21 days of treatment, blood samples were collected and the serum was subjected to estimate different biochemical parameters viz. blood glucose, cholesterol, urea and triglycerides level. Results: The solvent extracts were found to exhibit qualitative difference in phytochemical constituents There was a steep decline in blood glucose, cholesterol and triglycerides level when in methanolic extract of C.dactylon was given to experimental animals when compared with negative control. Moreover, petroleum ether and chloroform extracts also reduced the elevated plasma cholesterol and urea level in diabetic rats. Conclusion: It may be concluded that C. dactylon might be used in the treatment of diabetics. However, necessary studies on characterization of active principles and their mode of action are required for effective use of plant based drugs as antihyperglycemic agent.
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In the last few years, there has been an exponential growth in the field of herbal medicine and gaining popularity both in developing and developed countries because of their natural origin and less side effects. A comprehensive review was conducted to pile up information about medicinal plants used for the treatment of diabetes mellitus. It is a metabolic disorder of the endocrine system and affecting nearly 10% of the population all over the world also the number of those affected is increasing day by day. The profiles presented include information about the scientific and family name, plant parts and test model used, the degree of hypoglycemic activity, and the active chemical agents. The large number of plants described in this review (108 plant species belonging to 56 families) clearly demonstrated the importance of herbal plants in the treatment of diabetes. The effects of these plants may delay the development of diabetic complications and correct the metabolic abnormalities. This work stimulates the researchers for further research on the potential use of medicinal plants having antidiabetic potential.
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Diabetes mellitus is a disease that affects not only glucose metabolism but also mineral metabolism. This study was conducted to evaluate the effects of vitamin C and E on blood glucose and electrolyte levels in fructose-induced hyperglycemia in Wistar rats. Twenty (24) Wistar rats were usedfor the study. Each animal, regardless of their weight was made diabetic by feeding them with 20% (20g/100ml) of fructose dissolved in distilled water for a period of six (6) weeks, after which they were randomly assigned into four groups of six (6) animals each as follows: Group 1 served as diabetic control, Group 2 and 3 were treated with 100mg/kg b w of vitamin C and vitamin E respectively while Group 4 were treated with 250mg/kg b w of metformin and served as a positive control. All doses were administered orally once daily for a period of seven days. The results showed a statistically significant reduction (p<0.05) on blood glucose level in the groups treated with 100mg /kg b w of Vitamin C and E after day 3 and 7 when compared to control group. The result obtained also demonstrated a significantly reduced (p<0.05) serum sodium ion level in all groups treated with 100 mg/kg b w of vitamin C and E respectively when compared to diabetic control group. In regards to serum potassium ion, only Vitamin C at tested dose of 100mg/kg b w produced a significant change when compared to diabetic control group. However, the serum biocarbonate level was significantly decrease (p<0.05) in all groups treated with Vitamin C (100 mg/kg b w) and Vitamin E (100 mg/kg b w) respectively when compared to control group non treated group.
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Objective: To evaluate the in vivo antioxidant and antidiabetic activity of the methanolic bark extract of Tectona grandis Linn. (Family: Verbenaceae). Methods: The albino rats divided into four groups (Normal, Diabetic control, Diabetic+TGM (150mg) and Diabetic+TGM(300mg)) and the diabetic was induced by alloxan (120mg/kg i.p) and treated with TGM for 20 days. Then the antioxidant and antidiabetic parameters were evaluated by standard protocol. Results: The altered parameters i.e., blood glucose, glycosylated hemoglobin, protein, total cholesterol, urea, Serum creatinine, Aspartate Transaminase (AST), Alanine Transaminase (ALT), Lactate Dehydrogenase (LDH), Thiobarbituritic acid resactive substances (TBARS), Superoxide dismutase (SOD), Catalase and Glucose 6 phosphatase (G6P) were significantly (p<0.05) significantly (p<0.05) controlled by TGM (300mg/kg). Conclusion: The methanolic bark extract of Tectona grandis Linn. showed potent antioxidant and antidiabetic in alloxan induced diabetic rats and it can be used for the drug discovery development.
Objective: The present study was to evaluate antidiabetic activity of Padina boergesenii extract in streptozotocin (STZ) induced diabetic rats. Methods: Oral administration of the effective dose of P. boergesenii to the diabetic rats for 20 days showed abridged effects on fasting blood glucose, insulin and lipoprotein levels. Results: Significant difference was observed in liver glycogen and total protein levels in diabetic rats after P. boergesenii extract treatment (p<0.005). The extract of P.boergesenii significantly increased the activities of the key glycolytic enzymes like hexokinase, aldolase and phosphoglucoisomerase and decreased the activities of gluconeogenic enzymes like flucose-6-phosphatase and fructose -1, 6-diphosphatase in liver and kidney of experimental rats. Conclusions: P. boergesenii shows to have a potential value for the development of an effective phytomedicine for diabetes. Further comprehensive chemical and pharmacological investigations are needed to elucidate the exact mechanism of the hypoglycemic effect of P. boergesenii and compounds are accountable for its antidiabetic effect.
Diabetes is a major and growing public health challenge which threatens to overwhelm medical services in the future. Type 2 diabetes confers significant morbidity and mortality, most notably with target organ damage to the eyes, kidneys, nerves and heart. The magnitude of cardiovascular risk associated with diabetes is best illustrated by its position as a coronary heart disease risk equivalent. Complications related to neuropathy are also vast, often working in concert with vascular abnormalities and resulting in serious clinical consequences such as foot ulceration. Increased understanding of the natural history of this disorder has generated the potential to intervene and halt pathological progression before overt disease ensues, after which point management becomes increasingly challenging. The concept of prediabetes as a formal diagnosis has begun to be translated from the research setting to clinical practice, but with continually updated guidelines, varied nomenclature, emerging pharmacotherapies and an ever-changing evidence base, clinicians may be left uncertain of best practice in identifying and managing patients at the prediabetic stage. This review aims to summarize the epidemiological data, new concepts in disease pathogenesis and guideline recommendations in addition to lifestyle, pharmacological and surgical therapies targeted at stopping progression of prediabetes to diabetes. While antidiabetic medications, with newer anti-obesity medications and interventional bariatric procedures have shown some promising benefits, diet and therapeutic lifestyle change remains the mainstay of management to improve the metabolic profile of individuals with glucose dysregulation. New risk stratification tools to identify at-risk individuals, coupled with unselected population level intervention hold promise in future practice.
We have shown recently that oxidative stress by chronic hyperglycemia damages the pancreatic β-cells of GK rats, a model of non-obese type 2 diabetes, which may worsen diabetic condition and suggested the administration of antioxidants as a supportive therapy. To determine if natural antioxidant α-tocopherol (vitamin E) has beneficial effects on the glycemic control of type 2 diabetes, GK rats were fed a diet containing 0, 20 or 500 mg/kg diet α-tocopherol. Intraperitoneal glucose tolerance test revealed a significant increment of insulin secretion at 30 min and a significant decrement of blood glucose levels at 30 and 120 min after glucose loading in the GK rats fed with high α-tocopherol diet. The levels of glycated hemoglobin A1c, an indicator of glycemic control, were also reduced. Vitamin E supplementation clearly ameliorated diabetic control of GK rats, suggesting the importance of not only dietary supplementation of natural antioxidants but also other antioxidative intervention as a supportive therapy of type 2 diabetic patients.