Int.J.Curr.Microbiol.App.

Sci (2016) 5(11): 795-810

International Journal of Current Microbiology and Applied Sciences

ISSN: 2319-7706 Volume 5 Number 11 (2016) pp. 795-810
Journal homepage: http://www.ijcmas.com

Original Research Article http://dx.doi.org/10.20546/ijcmas.2016.511.091

Diabetes Mellitus and its Control by Ocimum sanctum

Extract in Mice Diabetic Model
Utsav1, Baidyanath Kumar2* and Atul Kumar3
1
Research scholar, Department of Biotechnology, Maharishi Markendeshwar University,
Mullana, Ambala (Haryana), India
2
Visiting Professor, Department of Biotechnology, Patna Science College, Patna (Bihar), India
3
Research Scholar, Department of Biotechnology, College of Commerce (MU), Patna, India
*Corresponding author

ABSTRACT

Diabetes mellitus is the most prevalent metabolic syndrome world- wide and is
characterized by hyperglycemia resulting in various short- term metabolic changes
Keywords in lipid and protein metabolism and long- term irreversible vascular changes which
Diabetes mellitus, include diabetic- specific complications viz., retinopathy, nephropathy and
Ocimum sanctum, neuropathy. Diabetes mellitus (DM) is a metabolic disorder of multiple etiologies
Streptozotocin, characterized by absolute or relative deficiency of insulin secretion with or without
Antidiabetic, varying degree of insulin resistance. Sedentary life style and obesity are two major
Mice. epidemiological determinants of diabetes mellitus. In the present investigation
hypoglycemic efficacy of Ocimum sanctum methanol extract was tested on STZ
Article Info induced mice diabetic models. The results clearly indicated that the diabetic control
Accepted: (DC) mice presented a significant lowering of body weight (p<0.001) when
26 October 2016 compared with the normal control (NC) mice. The DC mice showed a significantly
Available Online:
10 November 2016
(p<0.001) higher level of glucose (+279%), when compared with their normal
control counterparts. Diabetic mice of both of the groups (DT150 and DT250)
showed a reduction in glucose levels, when compared to the DC ones. The results
clearly indicated that the O. sanctum whole plant methanol extract is antidiabetic in
nature due to the presence of different types of active phytochemicals.

Introduction
Diabetes mellitus is a syndrome with and these patients are prune to ketoacidosis.
disordered metabolism and inappropriate Type- 2 diabetes is the more prevalent form
hyperglycemia due to either a deficiency of and results from insulin resistance with a
insulin secretion or to a combination of defect in compensatory insulin secretion.
insulin resistance and inadequate insulin
secretion to compensate. There are two In over 90%of cases Type- 1 diabetes is
classes of diabetes mellitus, Type- 1 and immune- mediated and in less than 10%
Type- 2. Type- 1 diabetes is due to cases it is idiopathic. The rate of pancreatic
pancreatic islet B cell destruction B cell destruction is quite variable. Type- 1
predominantly by an autoimmune process, diabetes is usually associated with ketosis in

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its untreated state. It occurs most commonly damage caused by viruses such as mumps or
in juveniles, with highest incidence among coxsackie B4 virus, by toxic chemical
the 10 to 14- year- old group, but agents, or by destructive cytotoxins and
occasionally occurs in adults, especially the antibodies released from sensitized
non obese and those who are elderly when immunocytes. Specific HLA immune
hyperglycemia first appears. It is a catabolic response genes are believed to predispose
disorder in which circulating insulin is patients to a destructive autoimmune
virtually absent, plasma glucagon is response against their own islet cells (auto
elevated, and the pancreatic B cell fail to aggression) which is mediated primarily by
respond to all insulinogenic stimuli. cytotoxic T cells. In such patients
Exogenous insulin is therefore required to immunosuppressive agent (e.g.
reverse the catabolic state, prevent ketosis, cyclosporine) is given to ameliorate
reduce the hyperglucagonemia, and reduce hyperglycemia.
blood glucose.
Type- 2 diabetes represents a heterogeneous
Certain human leukocyte antigens (HLA) group comprising milder forms of diabetes
are strongly associated with the that occur predominantly in adults but
development of Type- 1diabetes (Umesh occasionally in juveniles. More than 90% of
Masharani and John (2003). About 95% of all diabetics are included under this
Type- 1 patients possess either HLA- DR3 classification. Circulating endogenous
or HLA- DR4, compared with 45%- 50% of insulin is sufficient to prevent ketoacidosis
Caucasian controls. HLA- DQ genes are but is inadequate to prevent hyperglycemia
even more specific markers of Type- 1 in the face of increased needs owing to
susceptibility, since a particular variety tissue insensitivity. In most cases of this
(HLA- DQB1*0302) is found in the DR4 type of diabetes, the cause is unknown.
patients with Type- 1, while a “protective”
gene (HLA- DQBI*0602) is often present in Tissue insensitivity to insulin has been noted
the DR4 controls. In addition, circulating in most Type- 2 patients irrespective of
islet cell antibodies have been detected in as weight and has been attributed to several
many as 85% of patients, and the majority of interrelated factors. These include a putative
these patients also have detectable anti- genetic factor, which is aggravated in time
insulin antibodies prior to receiving insulin by additional enhancers of insulin resistance
therapy (Umesh Masharani and John Karam, such as aging, a sedentary lifestyle, and
2003). Most islet cell antibodies are directed abdominal- visceral obesity. In addition,
against glutamic acid decarboxylase, an there is an accompanying deficiency in the
enzyme localized within pancreatic B cells. response of pancreatic B cells to glucose.
Both the tissue resistance to insulin and the
Immune- mediated Type- 1 diabetes is felt impaired B cell response to glucose appear
to result from an infectious or toxic insult to to be further aggravated by increased
persons whose immune system is genetically hyperglycemia, and both defects are
predisposed to develop a vigorous ameliorated by treatment that reduces the
autoimmune response either against altered hyperglycemia towards normal. Most
pancreatic B cell antigens or against epidemiologic data indicate strong genetic
molecules of the B cell resembling the viral influences in Type- 2 diabetes. The genetic
protein (molecular mimicry). Extrinsic factors responsible for Type- 2 diabetes have
factors that affect B cell function include not yet been identified, though linkage to a

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gene on chromosome 2 encoding a cysteine adequate compensation for this insulin

protease, calpain- 10 has been reported in a resistance, nonketotic mild diabetes occurs.
Mexican- American population. The primary problem is a “target organ”
disorder resulting in ineffective insulin
Diabetes mellitus has been classified into action that can secondarily influence
some other specific types. pancreatic B cell function.

Maturity- onset diabetes of the young Chronic Complications of Diabetes

(MODY): This subgroup is a relatively rare
monogenic disorder characterized by non- Diabetes mellitus is associated with late
insulin- dependent diabetes with autosomal clinical manifestations that include a number
dominant inheritance and an age at onset of of pathologic changes that involve small and
25 years or younger. Patients are nonobese, large blood vessels, cranial and peripheral
and their hyperglycemia is due to impaired nerves, and the lenses of eye. These lesions
glucose- induced secretion of insulin. lead to hypertension, renal failure
(nephropathy), blindness (retinopathy),
Diabetes due to mutant insulin: This is a autonomic and peripheral neuropathy,
very rare subtype of nonobese Type- 2 amputations of the lower extremities,
diabetes. Since affected individuals were myocardial infarction, and cerebrovascular
heterozygous and possessed one normal accidents.
insulin gene, diabetes was mild, and showed
autosomal dominant genetic transmission. Type- 2 diabetes is the commonest form of
diabetes constituting 90% of the diabetic
Diabetes due to mutant insulin receptors: population. The global prevalence of
In more than 40 people with diabetes, diabetes is estimated to increase to 5.4% by
defects in one of their insulin receptor gene the year2025 (King Aubert and Herman,
have been observed. 1998). The World Health Organization has
predicted that the major burden will occur in
Diabetes mellitus associated with a the developing countries. The countries with
mutation of mitochondrial DNA: the largest number of diabetic people are,
Diabetes due to a mutation of mitochondrial and will be India, China and United States in
DNA that impairs the transfer of leucine or 2025 (King and Herman, 1998).
lysine into mitochondrial proteins has been Epidemiological studies among migrant
described. Most patients have a mild form of Asian Indians showed higher prevalence of
diabetes that responds to oral hypoglycemic Type- 2 diabetes compared with the host
agents. Two- thirds of patients with this populations and other migrant ethnic groups
subtype of diabetes have a hearing loss, and (Zimmet, 1999). Studies conducted in India
a smaller proportion had a syndrome of have highlighted that not only is the
myopathy, encephalopathy, lactic acidosis, prevalence of Type- 2 diabetes high, but also
and stroke- like episodes (MELAS). that it is increasing rapidly in the urban
population (Mohan et al., 2001; Raman
Obese Type- 2 patients: The most common Kutty et al., 2000; Misra, 2001; Verma and
form of diabetes is secondary to extra Madhu, 2000; and Iyer, 2000). The burden
pancreatic factors that produce insensitivity of Type- 2 diabetes and its complications
to endogenous insulin. When an associated related to Indian scenario has been
defect of insulin production prevents illustrated by Ramachandran et al., (2002).

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The genetics of Type- 2 diabetes has been spanned approximately 60 cR3000. Using
reviewed by Torben Hansen (2002). Beck- markers within the region, 418 unique
Nielson and Groop (1994) have suggested P1derived artificial chromosomes (PACs)
that the diabetic phenotype is the result of have been isolated and used to localize the
interaction of both genetic component and distal breakpoints of the two duplications.
an important non- genetic component. Linkage analysis of the familial case with
abnormal karyotype identified a
The coexistence of obesity, glucose recombination within the critical region.
intolerance, dyslipidemia, and hypertension, This recombination has been identified on
is termed as insulin resistance syndrome the radiation hybrid map and defines the
(IRS). Gerald Reaven (1988) initially proximal end of the region of interest. They
proposed that resistance to insulin- mediated therefore propose that an imprinted gene for
glucose disposal is the pathophysiological TNDM lies within an 18.72 cR3000
interface for several complex metabolic (~5.4Mb) interval on chromosome 6q24.1-
alterations and disease. Insulin resistance q24.3between markers D6S1699 and
syndrome in Asian Indians has been D6S1010.
reviewed by AnoopMisra and Naval k.
Bikram (2002). Regarding chromosomal Vladimir Bakalov et al., (2009) have
abnormalities deletion syndrome due to investigated that Turner syndrome (TS) is
chromosome 22q11.2 has been investigated caused by the absence or fragmentation of
by Elder et al., (2001). the second sex chromosome, which is
associated with increased risk of diabetes
Transient neonatal diabetes mellitus mellitus (DM), but the specific phenotype
(TNDM) is a rare condition which and genetic etiology of this trait are
represents with intrauterine growth unknown.
retardation, dehydration, and failure to
thrive. The condition spontaneously resolves Cytogenetic factors related with diabetes
before1 year of age but predisposes patients have been largely reviewed by (Bekalov et
to Type- 2 diabetes later in life. Rebecca J al., 2004; Salgin et al., 2006; Song et al.,
Gardner et al., (1999) have previously 2008; Neve et al., 2005; Senee et al., 2006;
shown that, in some cases, TNDM is Zhao et al., 2005; Mokhtari et al., 2008 etc).
associated with paternal uniparentaldisomy Suheir Assady (2009) has suggested the
(UPD) of chromosome 6and suggested that stem cell based therapy of diabetes mellitus.
an imprinted gene responsible for TNDM
lies within a region of chromosome 6q. By The current therapy of this disorder includes
analyzing three families, two with exogenous insulin administration
duplications (family A and patient C) and (particularly in case of Type-1 diabetes
one with several affected subjects with mellitus), and oral hypoglycemic agents (for
normal karyotypes (family B), Elder et al., Type-2DM) which includes Metformin,
(2001) have further defined the TNDM Pioglitazone, Sulphonylurea etc. which may
critical region. In patient A, polymorphic have adverse effects in diabetic subjects.
microsatellite repeat analysis identified a Multiple risk factors for diabetes have been
duplicated region of chromosome 6, flanked identified (WHO, 2006). The greatest risk is
by markers D6S472 and D6S311. This impaired glucose tolerance, a precursor of
region was identified on the Sanger Centre‟s diabetes. Thus, a number of type 2 diabetes
chromosome 6 radiation hybrid map prevention trials have included subjects with
(http://www.sanger.ac.uk/HGP/Chr6) and

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impaired glucose tolerance. These trials muscle insulin resistance (Lister et al., 1999;
compared intensive lifestyle modifications Fine good et al., 2001; Bell, 2003; Bakris et
(e.g., diet, exercise and weight loss), OHAs al., 2003; Herz et al., 2003; Nesto et al.,
and placebo controls (Tuomilehto et al., 2003; Kelly et al., 1999; Lee et al., 2003),
2001; Knowler et al., 2002). Ayurvedic and intestinal lipase inhibitor or orlistat to
treatment known as Apatarpana (balanced inhibit fat absorption and promote weight
diet with restricted calories) and Santarpana loss in obese patients (Guerciolini, 1997;
(highly nutritious, high-calorie diet intended Hollander et al., 1998; Hanefeld and Sachse,
to increase weight) are recommended for 2002; Kelley et al., 2002).
patients with type 2 and type 1 diabetes,
respectively (Sharma and Chandola, 2011). Despite excellent potencies, these synthetic
antidiabetic drugs had presented unwanted
The Clinical Practice Guidelines for the therapeutic profiles ,marked by fluid
Prevention and Management of Diabetes retention, hypoglycemia at higher doses,
recommends a target glycosylated liver problems, lactic acidosis, weight gain
hemoglobin (HbA1c) concentration of 7.0% and potential cardiac hypertrophy. There is
or less for all patients with diabetes and, for also evidence that hyperglycaemia per se has
those in whom it can be safely achieved, a deleterious effects on beta cell function and
target HbA1c concentration in the normal insulin action (glucotoxicity). Thus, a
range, usually ≤ 6.0% (WHO, 2006). concerted effort to search more effective
Although nonpharmacologic therapy (e.g., drugs for T2DM has become the need of the
diet, exercise and weight loss) remains a time in terms of efficacy as well as safety
critical component in the treatment of due to the undesirable side effects of
diabetes, pharmacologic therapy is often synthetic drugs.
necessary to achieve optimal glycemic
control. Orally administered Over the past 25 years, 50% of prescription
antihyperglycemic agents (OHAs) can be drugs have been developed from natural
used either alone or in combination with products and their derivatives. These
other OHAs or insulin. Various classes of medicines have emerged as unique, safe,
OHAs are now available that target the effective, and relatively inexpensive
different pathophysiologic factors remedies producing minimal or no side
contributing to diabetes: α-glucosidase effects with tall claims of efficacy as add on
inhibitors to delay intestinal carbohydrate therapy (Heinrich et al., 2012). Herbal drugs
absorption (Lebovitz, 1997; Inzucchi, 2002; with antidiabetic activity can be classified
Bayraktar et al., 1996), biguanides to target into four categories according to their mode
hepatic insulin resistance (Bailey and of action The first group has
Turner, 1996; Kirpichnikov et al., 2002; insulinomimetic effect and includes plant
Zhou et al., 2001; Holmes et al., 1999; like Momordica charantia (bitter gourd)
Salpeter et al., 2004), insulin secretagogues (Grover and Yadav 2004). Second group
to increase pancreatic insulin secretion acts on the β-cells to increase the production
(Klepzig et al., 1999; Lebovitz, 2001; Strom of insulin and include plants like Allium
et al., 2003; Hatorpe, 2002; McLeod, 2004), cepa (onion) and Pterocarpus marsupium
insulin sensitizers or thiazolidinediones (Vijaysaar) (Grover and Vats, 2001). The
which function as ligands for the third one enhances glucose utilization in
peroxisome proliferator-activated receptor diabetic patients and includes plants like
gamma (PPARγ) to target adipocyte and Gingiber officinale (ginger), Cyamospsis

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tetragonalobus (Gower plant) and Grewia Leading phytochemical compounds in holy

asiatica (phalsa). They increase the viscosity basil leaf include eugenol (volatile oil),
of gastrointestinal contents, slow gastric ursolic acid (triterpenoid) and rosmarinic
emptying and act as a barrier to diffusion acid (phenylpropanoid). The leaf of OS
(Grover and Vats, 2001). contains 0.7% volatile oil comprising about
71% eugenol and 20% methyl eugenol. The
Fourth group act by miscellaneous oil also contains carvacrol and sesquiterpine
mechanisms and include plants like hydrocarbon caryophyllene. Fresh leaves
Euphorbia prostrata, Fumaria parvia, and stem of OS extract yielded some
Panax ginseng and Phyllanthus embelica. phenolic compounds (antioxidants) such as
They may alter the fiber content and thereby cirsilineol, circimaritin, isothymusin,
altering the rate and speed of absorption of apigenin and rosameric acid and appreciable
glucose from the gut (Grover and Vats, quantities of eugenol. Two flavonoids, viz.,
2001). The isolation and formulation of orientin and vicenin from aqueous leaf
active constituents from these plants along extract of OS have been isolated ursolic
with their pharmacological and toxicological acid, apigenin, luteolin, apigenin-7-O-
evaluation are the need of the modern glucuronide, luteolin-7-O glucuronide,
therapeutics. orientin and molludistin have also been
isolated from the leaf extract. OS also
Pallab Das Gupta and Amartya De (2012) contains a number of sesquiterpenes and
have compiled some herbal plants and their monoterpenes viz., bornyl acetate, α-
active ingredients which play an important elemene, neral, α- and β-pinenes, camphene,
role in the management of diabetes mellitus. campesterol, cholesterol, stigmasterol and β
The antidiabetic properties of Bitter melon -sitosterol (Indian Herbal Pharmacopoeia,
(Momordica chantrantia), Fiery costus 2012). Other active compounds include
(Costus igneus), Dendelium (Taraxacum caryophyllene and oleanolic acid. Seeds
officinale), French Lilac (Golega contain fixed oiks having linoleic acid and
officinalis), Termeric (Curcuma longa), Bael linolenic acid. Nutritional components
(Aegle marmelus), Amla (Emblica include vitamins A and C; minerals calcium,
officinalis), Fenugreek (Trigonella foenum- iron and zinc; as well as chlorophyll. It
gracum), Ginseng (Panax ginseng), contains no caffeine or other stimulants.
Nayantara (Catharanthus roseus), Neem Holy basil is highly aromatic and different
(Azadirachta indica), Cinnamon varieties may smell and taste of peppermint,
(Cinnamomum zeylanicum), black berry cloves, licorice or lemon. The clove-like
(Rubus fruticosus) etc. have been greatly odor comes from its high eugenol content.
illustrated (Shukla, 2000; Wadkar, 2008; Eugenol is a phenolic compound and major
Rakesh et al., 2009; Zhijun Song et al., constituent of essential oils extracted from
1997; Mushtaq Ahmad et al., 2009; different parts of Tulsi plant. Ocimum
M.UpendraRao, 2010; Kavishankar, 2011; sanctum known as „Tulsi‟ in hindi and „Holy
Suresh Kumar et al., 2012; Manisha Modak, Basil‟ in English, is an erect softy hairy
2007 etc.) aromatic herb or under shrub found
throughout India. Two types of Ocimum
Ocimum sanctum of family Labiatae sanctum are met within cultivation: (i) Tulsi
(Lamiaceae) is indigenous to the tropical plants with green leaves known as Sri Tulsi
regions of Asia and the America and wildly & (ii) Tulsi plants with purple leaves known
cultivated in India. as Krishna Tulsi. Ocimum sanctum is held

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sacred by Hindus and is used as medicinal hygienic conditions in the departmental

plants in day to day practice in Indian homes animal house during experimental period.
for various ailments. The mice were allowed to acclimatize for
15 days in an environmentally controlled
The hypoglycemic effects of Ocimum room under standard environmental
sanctum extract on mice diabetic models has conditions (21±2°C, 55±5% Relative
not been evaluated so far and hence the humidity, 12 hr Light: Dark cycle).
present investigation was undertaken.
The mice were fed on diet consisted of
Materials and Methods wheat grains-1Kg, Choker wheat-250gm,
Gram grains-250gm, Maize grains-250gm,
Methanol extract of Ocimum sanctum Linn. Soybean grains-250gm, Sundrop oil-50gm,
(Lamiaceae) was used for assaying Milk powder-2 table spoon and Jaggery-
hypoglycemic activities in Streptozotocin 50gm. This diet provided carbohydrate
induced mice diabetic models. The plant 48.3%, crude protein 23.5%,crude fat5.9%
Ocimum sanctum was collected from crude ash5.9% and crude fibre 3.9% (W/W).
campus of Patna Science College, Patna and
identified following relevant monographs of In each cage one pellet of feed per mice was
Indian Pharmacopoeia (2012). Freshly given. The diet was palatable to the animal
harvested plant materials (root, stem, leaves as evidenced by feeding success. It has been
and flowers) were washed under running tap observed that an adult mice normally intakes
water, blotted with filter paper and was dried 4 to 5 gram of diet per day. The daily food
in the shade at room temperature. The dried consumption of the mice varied depending
plant sample (2.6 kg) was then soaked with upon the physiological and health status of
absolute methanol under reflux condition for the mice as well as the environmental
the methanolic extract preparation. The temperature. The consumption of food
sample was then homogenized with increased considerably when the mice were
extraction buffer and the supernatant pregnant or at lactating stage and decreased
collected after three rounds of extraction. considerably with the dose-duration and
The solvent was evaporated under reduced increased temperature in summer.
pressure in a rotary evaporator at 40 0C. To
this thick paste colloidal silicon dioxide was The animal model for the present study was
added and dried in vacuum tube dryer. The based on multiple administration of low
obtained methanol extract was stored in dose of freshly prepared streptozotocin
deep freezer at _200 C until further test. (STZ). For induction of diabetes, initially
the normal mice were kept 24 hours without
Significant insights into the etiology of food and water. The weight of normal mice
diabetes in human have been gained from was determined. Diabetes was induced by
the study of animal models. The albino multiple intra-peritoneal injection of freshly
mouse is an excellent model for study of prepared STZ solution in 0.05 M sodium
human diabetes. Therefore all mice used in citrate (pH 4.5) at the dose of 35 mg/kg
this study were in the albino genetic body weight followed by an hour of fasting.
background. Adult albino mice weighing The mice were then allowed to access the
around 17–20 gram with 6.5 ± 0.5 cm length respective food and water ad libitum. Mice
are selected for experiments. The mice were with fasting blood glucose level of
housed in shoe-box type cages under good 200 mg/dl (7.8 mmol/l) or higher were

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considered to be diabetic and were used in Data were statically analyzed by mean ± S.E
the study. A parallel set of control mice and by one-way ANOVA.
(non-diabetic) were injected with citrate
buffer only. The results related to body weight change
and blood glucose level in mmol/l in mice
The mice were grouped into five categories during present course of investigation have
viz., Normal control (NC), Diabetic Control been presented in Table-1 and 2.
(DC), Diabetic Treated (DT150), Diabetic
Treated250) and Diabetic Treated (DTPGZ). Results and Discussion
NC received only citrate buffer solution. DC
group was STZ induced which received The whole plant extract of Ocimum sanctum
citrate buffer only. DT150 and DT250 received has been reported to be effective in
150mg/Kg and 250mg/Kg body weight of alleviating diabetes mellitus through its
methanol extract respectively. DTPGZ antioxidant and insulin- potentiating
received Pioglitazone at a dose of 2mg/Kg activities (Okoli et al., 2010). In the present
of body weight. All the mice were fed with investigation the effect of methanol extract
common pellet diets for 2 weeks after of Ocimum sanctum on body weight of mice
arrival, and then randomly divided into two was studied. The results clearly indicated
groups. One group continued to receive that the diabetic control (DC) mice
common pellet diets and constituted the presented a significant lowering of body
normal group; the other was fed with diets weight (p<0.001) when compared with the
high in fat and fructose, in order to induce normal control (NC) mice (Table- 1& Fig.
type-2 diabetes. All the mice had free access 1). A significant gain in body weight was
to food and water. observed in the treated groups of diabetic
mice (DT150 and DT250) as compared to the
For the experiment, the mice were divided DC ones. The DT150 and DT250 group
into five groups having six mice in each showed an increase of 28% and 39% in body
group: DC group (diabetic control mice), weight respectively after 15 days of
NC group (non-diabetic control mice) and treatment. Contrary to this, DTRGZ group
three DT group (diabetic mice treated with mice showed an increase of 50% in body
two different doses of extract as well as weight after 15 days of treatment (Table-1&
Pioglitazone/ kg body weight). Body Fig. 1).
weights were recorded weekly during the
experimental period. Treatment with The changes in the blood glucose levels
extracts was started after one week of STZ before and after receiving the treatment in
treatment, which was considered as the 1st normal and diabetic mice have been
day of treatment. Blood samples were taken presented in Table -2 and Figure 2. As
after 8 hrs fasting from the retro-orbital expected, the DC mice showed a
sinus vein prior to the administration of test significantly (p<0.001) higher level of
substances or the buffer and 4 weeks after glucose (+279%), when compared with their
the treatment under mild ether anesthesia normal control counterparts. Diabetic mice
and allowed to clot for 30 minutes at room of both of the groups (DT150 and DT250)
temperature. Blood samples were showed a reduction in glucose levels, when
centrifuged at 3000 rpm for 20 minutes. compared to the DC ones; nevertheless, the
Serum was separated and stored at -20°C reduction was particularly evident in the
until biochemical estimations were carried DT250 mice (−44%; p<0.001). When
out.

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compared, the glucose levels of the DT250 indicate potential antidiabetic action of O.
versus the DC group mice during the 4-week sanctum (Raphael et al., 2000).
treatment program, a significant lower value
in the first was also found (−45%; p<0.001) Diabetes has a significant impact on the
respectively (Table-2& Fig. 2). health, quality of life and life expectancy of
Nevertheless, this decline in the glucose patients as well as healthcare expenditure.
levels was less evident in the DT150 mice With increasing incidence and mortality
(−38%) than in the DT250 mice. In contrast from its complications, prompt and adequate
to this, DTPGZ group mice showed almost glycemic control in diabetes is paramount if
67% decline in glucose level after 4-weeks management can meaningfully improve the
of treatment program (Table -2& Fig. 2). quality of life and increase life expectancy
(Nyenwe et al., 2011).
Phytochemicals from natural products
possess potent antioxidant activity that are Several studies to test new drugs with
capable of prevention of the onset and/or potential antidiabetic activity were used in
progression of many human diseases by animal models of streptozotocin (STZ)-
counteracting reactive oxygen species induced diabetes (Fröde and Madeiros,
(ROS) (Palasuwan et al., 2005; Cai et al., 2008). Although none of the chemically-
2006; Bouayed et al., 2007; Liu et al., induced diabetic models can reproduce the
2007). An alcoholic extract of O. sanctum complexity of the human disease, they can
was found to reduce significantly the blood be helpful to understand at least some
sugar in normal mice and in STZ induced aspects of the potential bioactivities of
diabetes mice. In normal mice, natural or synthetic products. We used
administration of O. sanctum 200mg/kg diabetic albino mice induced by STZ (35
body weight reduced the blood sugar by mg/kg body wt.), which was sufficient to
34.5 percent and to 47.4 percent at the induce a stable state of diabetic condition in
concentration of 1000mg/kg by weight at 1 this animal species.
hour. However at 6th hour, values are
almost similar to normal value. Continuous Induction of diabetes with streptozotocin is
administration of the drug produced associated with a characteristic loss of body
significant reduction in normal blood sugar weight, which is probably due to muscle
in mice, which on 15th day was also found wasting. In the present investigation there
to reduce the blood sugar in streptozotocin was a significant weight loss in the vehicle
diabetic mice. In short term experiment, treated diabetic mice, where as treatment
drug was found to reduce the blood sugar at with the O. sanctum extract at three doses
4th hour by 6.07 percent at dose level of showed improvement in their body weight,
200mg/kg by weight and 18.7 percent at indicating that the methanolic extract of O.
concentration of 1000mg/kg by weight. sanctum had beneficial effect in preventing
Continuous administration of drug produced loss of body weight of diabetic mice. The
significant reduction in blood sugar in probable mechanism of this benefit is due to
streptozotocin diabetic mice. On 15th day its effect in controlling muscle wasting, i.e.,
values were almost similar to normal in the by reversal of antagonism. The metabolic
group taking 1000 mg/kg by weight. Plant disturbances were corrected after the plant
extract did not produce any toxicity as seen extract was administered at the two different
from liver and kidney function test and in dose of 150 and 250 mg/kg body weight for
hematological parameters. The results four weeks as shown by a reduction in

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biochemical parameters in diabetic mice and to investigate its mechanisms of actions.

treated with plant extract. This result is in Hence, in the present study, the two defined
accordance with Lenzen S. (2008) and doses of methanolic extract of whole plant
Chung et al., (2003). They have found that of O. sanctum have been investigated for
multiple low dose of STZ sufficiently induce their antidiabetic potential.
stabilized acute diabetes in which there is a
progressive deterioration in the glucose Chronic hyperglycaemia in diabetes is a risk
tolerance and insulin secretion after the STZ factor constantly fuelled by postprandial
injection. It ultimately causes increased elevation of blood glucose. Control of
oxidative stress, which play an important postprandial hyperglycemia in diabetes is of
role in the pathogenesis of various great importance due to its close relation to
complications. The present findings are also the risk of micro and macro-vascular
in accordance with Santwana Rani and complications and death (Nyenwe et al.,
Baidyanath Kumar (2015) who found a 2011). In the present investigation,
more or less similar results of Phyllanthus experimental evaluation of the
niruri methanol extract on Streptozotocin hypoglycemic potentials of O. sanctum has
induced mice diabetic models. Atul et al., shown that the higher dose of extract (250
(2014) have found the efficacy of Trigonella mg/kg body wt.) suppress postprandial rise
foenum gracum and Costus igneus in the in blood glucose levels more effectively than
management of type-2 diabetes mellitus in lower dose of extract (150 mg/kg body wt.)
11 subjects. which is the index of effectual glycemic
control. It may be due to alteration in the
Oral administration of Ocimum sanctum fiber content as well as phytochemical
extract led to marked lowering of blood interactions which thereby altering the rate
sugar in normal, glucose fed hyperglycemic and speed of absorption of glucose from the
and streptozotocin-induced diabetic rats gut. These favorable effects of O. sanctum
(Chattopadhyay, 1993). A randomized, extract may be attributed to higher affinity
placebo-controlled, cross over single blind and synergistic action of their
human trial indicated a significant decrease phytochemicals on multiple targets
in fasting and postprandial blood glucose including PPAR-γ activation and DPP-IV
levels by 17.6% and 7.3%, respectively. inhibition which may therefore regulate the
Urine glucose levels showed a similar trend hyperglycemia, lipogenesis and
(Agrawal, 1996). Further, OS has aldose hypertriglyceridemia associated with
reductase activity, which may help in diabetes (Shimizu et al., 2003; Barnett,
reducing the complications of diabetes such 2006).
as cataract, retinopathy, etc (Halder, 2003). In the hypoglycemic activity studies of
At present, several drugs are available for methanol extract, daily oral administration
the management of hyperglycemia but they of the extract for 28 days produced a gradual
are expensive and possess side effects also. but sustained reduction in blood glucose
Therefore, search for a suitable alternative is levels in diabetic treated mice.
continued. For the developing countries Streptozotocin causes hyperglycaemia and
herbal plants may be the most attractive glucose intolerance or syndromes similar to
target for their availability, low cost and either type 1 or type 2 diabetes (Frode and
better safety margin. The hypoglycemic Medeiros, 2008). Effective and sustained
activity of Ocimum sanctum L. has attracted reduction in blood glucose levels of treated
many researchers to prove it scientifically diabetic mice by the extract indicates that it
may be useful in overt cases of diabetes.
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Table.1 Showing body weight changes in mice during and after treatment
with methanol extract of O. sanctum
Non Diabetic Normal Control (NC) Day 0 Day7 Day15
19.98±2.86 21.80±2.41 24.85±2.26
Diabetic Mice
Diabetic Control (DC) 11.70±1.15 09.50±0.95 7.67±1.22
O. sanctum extract (150mg/Kg) (DT150) 11.71±2.03* 12.11±1.67* 13.75±1.54*
O. sanctum extract (250mg/Kg) (DT250) 11.68±1.63* 12.75±2.37* 14.85±2.65*
Pioglitazone (2mg/Kg) (DTPGZ) 11.70±3.74* 14.85±3.91* 16.24±1.85*

*significant as compared to control; n=6 in each group

Table.2 Showing effects of different doses of O. sanctum extract and

Pioglitazone on blood glucose levels in mice

Mice Groups Blood glucose levels in (mmol/l) in four different weeks

Pretreatment Post-treatment
0 1 2 3 4
Normal control (NC) 3.95±0.13** 4.07±0.14** 4.06±0.25** 4.05±0.16** 3.99±0.19**
Diabetic control (DC) 14.92±1.55* 14.91±1.48* 14.78±1.59* 14.96±1.49* 14.94±1.48*
O. sanctum extract (150mg/Kg) 14.95±1.45 13.04±1.18* 10.65±2.09** 9.65±1.28** 9.25±1.79**
DT150
O. sanctum extract (250mg/Kg) 14.65±1.56 11.86±1.38** 9.55±1.28** 8.20±1.74** 8.12±1.28**
DT250
Pioglitazone (2mg/Kg) DTPGZ 15.03±1.49 9.84±1.48** 5.57±1.28** 4.97±1.35** 4.94±0.97**

*p<0.05 as compared with normal control. **p<0.001 as compared with diabetic control.
Fig.1 showing change in body weight of mice after administration of
O. sanctum extract and PGZ

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Fig.2 showing effects of different doses of O. sanctum extract and Pioglitazone on blood glucose
levels in mice before and four weeks after administration

Treatment with the two doses of extract also a safe supplementary therapy for long- term
reduced mortality of diabetic mice from and effective management of diabetic
hyperglycaemia and prolonged their patients.
survival. In the present study, some of the
diabetic non-treated control animals all died Acknowledgement
on day 10 post-induction of diabetes
whereas the extract-treated group survived The authors are thankful to Dr. Baidyanath
beyond the period of the experiment. Kumar, Visiting Professor, Department of
Effective control of blood glucose level is a Biotechnology, Patna Science College,
key step in preventing and reversing diabetic ,Pa.tna (PU), for providing necessary
complications, and improving the quality of suggestion for the preparation of this
life of diabetic patients (Bavarva and research article.
Narasimhacharya, 2008). Hence, chronic
administration of the extract may cause a References
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How to cite this article:

Utsav, Baidyanath Kumar and Atul Kumar. 2016. Diabetes Mellitus and its Control by Ocimum
sanctum Extract in Mice Diabetic Model. Int.J.Curr.Microbiol.App.Sci. 5(11): 795-810.
doi: http://dx.doi.org/10.20546/ijcmas.2016.511.091

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