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INTRODUCTION

Diabetes mellitus (DM) is a chronic metabolic disorder. It is


characterized by hyperglycemia and glycosuria. It is a condition that
occurs when the body can't use glucose normally so sometimes it is
called "sugar diabetes". The glucose level in the blood is controlled by
the insulin hormone, which is made by the pancreas. It helps glucose
enter the cell.In this 21st century, Diabetes mellitus has become a global
pandemic affecting about 400 million people worldwide, where 69.2
million are Indians. The value is expected to double by 2030 according
to the data provided by the World Health Organization (WHO).
There are mainly two types of diabetes, Type1, and Type2 diabetes.
Type1 diabetes is called an autoimmune disease. The insulin-producing
cells in the pancreas are destroyed. It is usually diagnosed in young
adults and children. In type1 diabetes patients need to take insulin every
day so it is called insulin-dependent diabetes. In type2 diabetes, either
body's cells don't respond normally to insulin or do not make enough
insulin. It occurs in older or middle-aged people. So it is called adult-
onset diabetes. Prediabetes is the next stage of Type2 diabetes. In
prediabetes blood, glucose levels are higher than normal level and it is
not high enough to be diagnosed with type2 diabetes. Gestational
diabetes develops in pregnant women sometimes. It usually goes away
after pregnancy. It has a higher risk of developing type-2 diabetes later
on in life.
The symptoms of diabetes are mainly weak, tired feeling, blurred vision,
increased thirst, tingling in the hand or feet, slow healing sores, weight
loss, dry mouth, frequent unexplained infection, etc. In women, the
symptoms of diabetes mainly include dry and itchy skin, urinary tract
infection, etc. and In men, the symptoms of diabetes mainly include
decreased muscle length, decreased sex life, etc. In type1 diabetes
symptoms can develop quickly. The risk factor of type1 diabetes are
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having a family history, injury to pancreas or infection, tumor, surgery,
accident, presence of antibodies that mistakenly attack own body's tissue
or organs physical stress for surgery or illness, exposure to illnesses
which is caused by viruses, etc. The risk factors of tpe2 and prediabetes
are family history, being overweight, having high blood pressure and
low HDL cholesterol, high triglyceride level, physically inactive, stroke,
being a smoker, being older, etc. In gestational diabetes risk factors
include being over 25 years of age, family history, overweight before
pregnancy, etc.
The complications of diabetes are two types, Acute, and Chronic
complications. Acute complications include hypoglycemia, diabetic
ketoacidosis, hyperglycaemic diabetic coma, loss of consciousness, and
infection. IN chronic complications include Nerve damage,
cardiovascular issues like high blood pressure, chest pain, stroke, heart
attack, coronary artery disease, etc., kidney damage or kidney failure,
eye damage, depression, depression, hearing loss, dementia, dental
problems, etc. . In gestational diabetes in the mother, high blood
pressure, excess protein in the urine, foot swelling, etc. are occurring.
During future pregnancy and risk of diabetes later in life. In newborn
babies low blood sugar, higher than normal birth weight, higher risk of
developing type2 diabetes over time, and death shortly after birth also.
Lifelong insulin injections in different combinations, Glucometers to
self-monitor blood glucose, Early detection, and treatment of
complications like an eye exam, urine test, foot care, and specialist
referral as needed for type 1 diabetes Treatment. For type 2 diabetes
patients treated with either diet or exercise, or with the addition of one or
more categories of oral medications, with a combination of oral
medications and insulin, or with insulin alone. Glucometers are used to
self-monitor blood glucose. Early detection and treatment of
complications including eye exam, urine test, foot care, and specialist
referral as needed. Self-monitoring for symptoms of hypoglycemia and

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hyperglycemia, patient education about diet, exercise, and foot care is a
must.

Metformin might target the liver to reduce gluconeogenesis and skeletal


muscles to enhance peripheral glucose utilization, with a possible role in
the gut to increase levels of glucagon-like peptide 1 (GLP-1).
Sulfonylureas and meglitinides increase insulin secretion in the
pancreas.

There are many drugs used for their anti-diabetic action. The main
disadvantage of the currently available drugs is that they have to be
given throughout life without any permanent solution to diabetes or
oxidative stress and these types of medications are associated with side
effects and the cost of therapy in many cases is too expensive. The long-
term use of insulin results in prominent side effects like, anorexia
nervosa, brain atrophy, and fatty liver, etc. and it is not also affordable in
low-income countries. The medicinal plant and its bioactive constituents
can be used for T2DM treatment. These are less toxic, easily available,
and cost-effective. They are rich in different phytochemicals which can
exert antioxidants, free radical scavenging activities, etc. that have been
shown to improve insulin sensitivity and help to combat T2DM
complications. These medicinal plants interact directly with our body
chemistry without any side effects. There is an increasing demand by
patients to use natural products having anti-diabetic activity. Ipomea
Hedracea being one of them. Ipomea Hedracea (common name is
Morning Glory in Hindi), belonging to the family Convolvulaceae,
found in India, North America, etc. Different parts of this plant are used
widely in medicinal preparation to cure different diseases such as
abdominal diseases, fevers, headaches, and bronchitis. The
pharmacological properties such as diuretic, anthelmintic, blood purifier,
deobstruent, laxative, carminative and anti-inflammatory actions have
been ascribed to this plant. Traditional plant medicines are used
throughout the world for diabetes. There are many medicinal plants
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known to be used in the treatment of diabetes and some plants have been
screened positive for their antidiabetic effect. Most of these plants were
found to belong to the chemical groups of glycosides, alkaloids, and
flavonoids. I decided to perform this investigation to evaluate the anti-
diabetic action of its seed extraction against STZ induced diabetic rats.

Review of Literature

On 15th March 2011, Ramdas B. Pandhare (Department of


Pharmacognosy, TIT-Pharmacy, Bhopal, India ) published on
antidiabetic activity of aqueous leaves extract of Sesbania sesban (L)
Merr. in Streptozotocin-induced diabetic rats, the aqueous leaves extract
of Sesbania sesban (L) Merr. (Family: Fabaceae) was evaluated for its
antidiabetic potential on normal and streptozotocin (STZ)-induced
diabetic rats. In the chronic model, the aqueous extract was administered
to normal and STZ- induced diabetic rats at the doses of 250 and 500
mg/kg body weight (b.w.) p.o. per day for 30 days. The Fasting Blood
Glucose Levels (BGL), serum insulin level, and biochemical data such
as glycosylated hemoglobin, Total Cholesterol (TC), Triglycerides (TG),
High-Density Lipoproteins (HDL), and Low-Density Lipoproteins
(LDL) were evaluated and all were compared to that of the known anti-
diabetic drug glibenclamide (0.25 mg/kg b.w.). The statistical data
indicated a significant increase in the body weight, liver glycogen,
serum insulin, and HDL levels and a decrease in blood glucose,
glycosylated hemoglobin, total cholesterol, and serum triglycerides
when compared with glibenclamide. Thus, the aqueous leaves extract of
Sesbania sesban had beneficial effects in reducing the elevated blood
glucose level and lipid profile of STZ-induced diabetic rats.

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In MAY 2012 Marilena Meira IInstituto Federal de Educação, Ciência e
Tecnologia da Bahia, Campus Simões Filho, Brazil approximately 600-
700 species of Ipomoea, Convolvulaceae, are found throughout tropical
and subtropical regions of the world. Several of those species have been
used as ornamental plants, food, medicines, or in religious rituals. The
present work reviews the traditional uses, chemistry, and biological
activities of Ipomoea species and illustrates the potential of the genus as
a source of therapeutic agents. These species are used in different parts
of the world for the treatment of several diseases, such as diabetes,
hypertension, dysentery, constipation, fatigue, arthritis, rheumatism,
hydrocephalus, meningitis, kidney ailments, and inflammations. Some of
these species showed antimicrobial, analgesic, spasmolytic,
spasmogenic, hypoglycaemic, hypotensive, anticoagulant, anti-
inflammatory, psychotomimetic, and anticancer activities. Alkaloids,
phenolics compounds, and glycolipids are the most common biologically
active constituents from these plant extracts.

On 23rd Jan 2016 R. Sivaraj Department of pharmacology, Annamalai


University, Annamalai Nagar, Tamil Nadu, India, and B.Jayaprasad and
P.S.Sharavan Department of botany Annamalai Nagar, Tamil Nadu,
India published on the anti-diabetic effect of Chloroxylon swietenia bark
extract on a streptozotocin-induced rat. Diabetes has been increasing at
an alarming rate around the world, and experts have relied on remedies
from the utilization of ancient drugs that are essentially derived from
plants. The present study aimed to evaluate the antidiabetic potential
ofChloroxylon Swietenia bark extracts on streptozotocin-induced
diabetic rats. Diabetes was induced in male albino Wistar Rats by a
single intraperitoneal injection of streptozotocin (STZ) (50 mg/kg b.w.).
The diabetic rats were administered orally. Swietenia bark (CSB)
methanolic (CSBMEt) and aqueous(CSBAEt) (250 mg/kg b.w.) extracts
and glibenclamide (600μg/kg b.w.) by intragastric incubation for 45
days. The result showed a heavy loss in weight, an increase in blood
glucose and glycosylated hemoglobin level, and a decline in plasma

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insulin and total hemoglobin content. Furthermore, glucose-6-
phosphatase and fructose-1,6-bisphosphatase were found to be increased
whereas hexokinase and glycogen contents were decreased in STZ
induced diabetic rats. CSBAEt, CSBMEt, and glibenclamide treated
diabetic rats showed a moderate reduction in blood glucose and
glycosylated hemoglobin levels; in addition, plasma insulin and
hemoglobin levels were elevated. The altered activities of carbohydrate
metabolizing enzymes and liver glycogen were improved
remarkably.CSBMEt results were comparable to the standard drug
glibenclamide. The present findings support the usage of plant extracts
for the traditional treatment of diabetes.

On 23rd April 2019 Yohannes Kelifa Emiru School of Pharmacy,


College of Health Sciences, Mizan-Tepi University, Mizan Teferi,
Ethiopia published on the anti-diabetic and antihyperlipidemic effect of
Aloe megalacantha Baker (Aloaceae)in the streptozotocin-induced
model. Diabetes mellitus has become a major public health and
economic problem across the globe. The inadequacies, as well as serious
adverse effects associated with conventional medicines, led to a
determined search for alternative natural therapeutic agents. The leaf
latex extract of Aloe megalacantha has been used for the management of
diabetes mellitus in Ethiopian folk medicine. This study aimed to
evaluate the antidiabetic and antihyperlipidemic effects of the leaf latex
extract of A. megalacantha in a streptozotocin- (STZ-) induced diabetic
model. Methods. The experimental diabetes was induced in Swiss albino
mice by the administration of a single dose of STZ (150 mg/kg),
intraperitoneally. The leaf latex extract of A. megalacantha at three
different doses (100, 200, and 400 mg/kg) was administered for 14 days.
Fasting blood glucose levels (BGLs) were measured by glucose oxidase
and peroxidase reactive strips. After fourteen days, mice from all groups
fasted and the blood was collected by puncturing the retro orbit of the

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eyes under mild anesthetic conditions. The collected blood sample was
used to determine serum biochemical parameters such as total
cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL),
very-low-density lipoprotein (VLDL), and high-density lipoprotein
(HDL) cholesterol. The statistical analysis of results was carried out
using one-way analysis (ANOVA) followed by post hoc multiple
comparison tests. Results. Oral administration of A. megalacantha leaf
latex extract at doses of 100, 200, and 400 mg/kg daily for 14 days
results in a significant (p < 0.05) decrease in fasting BGL as compared
to negative control STZ-induced diabetic mice. The leaf latex has
significantly reduced the level of TC, TG, and LDL, VLDL cholesterol
while a significant (p < 0.05) HDL cholesterol increment was observed.
Conclusions. The findings of the present investigation indicated that the
leaf latex of A. megalacantha possessed significant antihyperglycemic
and antihyperlipidemic potential which may prove the claimed use of the
plant in amelioration of diabetes and associated complications in
Ethiopian folk medicine.

On 13th October 2014 Hyung-In-Moon Department of Medicinal


Biotechnology, Dong-A University, published on the effect of Osajin
and Pomiferin on Antidiabetic Effects from Normal and Streptozotocin-
induced Diabetic Rats. The present study evaluated the antidiabetic
effect of osajin and pomiferin from the osajin orange in normal and
streptozotocin-induced diabetic rats. Pomiferin in the streptozotocin-
induced diabetic effects showed significant hypoglycemic activity for 14
days significantly decreased the serum glucose, triglyceride while it
increased the serum insulin in diabetic rats but not in normal rats (p <
0.05; at doses of 100 and 300mg/kg for 14 days). Pomiferin showed
potential in anti-diabetic effects compared to osajin. It also has no
effects on C-peptide (ECLIA). Further structure-activity relationships of

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aromatic position 3 on ring B from osajin and pomiferin will be reported
in due course.

In Jan 2004 Sanjay P Akhani (Department of pharmacology, LM college


of pharmacy ) published on Anti-diabetic activity of Zingiber officinale
in streptozotocin-induced type I diabetic rats. The fresh and dried
rhizome of Zingiber officinale Roscoe (commonly known as ginger) is
widely used in traditional medicine. We have studied the effect of the
juice of Z. officinale (4 mL kg(-1), p.o. daily) for 6 weeks on
streptozotocin (STZ)-induced type I diabetic rats with particular
reference to the involvement of serotonin (5-hydroxytryptamine; 5-HT)
receptors in glycaemic control. In normoglycaemic rats, 5-HT (1mg kg(-
1), i.p.) produced hyperglycemia and hyperinsulinemia, which was
significantly prevented by the juice of Z. officinale. STZ-diabetes
produced a significant increase in fasting glucose levels that were
associated with a significant decrease in serum insulin levels. Treatment
with Z. officinale produced a significant increase in insulin levels and a
decrease in fasting glucose levels in diabetic rats. In an oral glucose
tolerance test, treatment with Z. officinale was found to significantly
decrease the area under the curve of glucose and to increase the area
under the curve of insulin in STZ-diabetic rats. Treatment with Z.
officinale also caused a decrease in serum cholesterol, serum
triglyceride, and blood pressure in diabetic rats. Our data suggest a
potential antidiabetic activity of the juice of Z. officinale in type I
diabetic rats, possibly involving 5-HT receptors.

In 2012 B.P.Singh and Sandhya Singh Department of Chemistry,


University Institute of Engineering & Technology, C.S.J.M. University,
Kanpur, India published on Chemical Investigation of Seed of Ipomoea
hederacea and its Biological Activity. Ipomoea is the largest genus in the
flowering plant family "Convolvulaceae" with over 500 species, most of
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these are called morning glories. Ipomoea hederacea considered a
valuable herb for indigenous medicine is renowned for its medicinal
properties. Ipomoea hederacea is a favored drug for different diseases
because of its oral effectiveness, good safety profile availability in India.
The seed of this plant has also been used in both analgesic and antiseptic
properties. The present work aims to investigate the phytochemical
investigations of different extracts of seed of Ipomoea hederacea. The
methanolic extract of seed was directly chromatographed over a silica
gel column eluted with solvent petroleum ether, chloroform, acetone,
and methanol to their increasing order of polarity. The various extracts
were directly separated by column chromatography and monitored by
thin-layer chromatography. The extracts were characterized based on
various spectral techniques such as IR, 1H NMR,
and mass spectroscopy. The antibacterial study was performed against
bacteria species via; Escherichia coli and pseudomonas aeruginosa. The
methanol extracts of seed of Ipomoea hederacea exhibited a varying
level of antibacterial activity, with minimum inhibitory concentration
(MIC) of 2 mg/ml against both bacteria. The methanol extract was found
to be more active than the other extract like petroleum ether, chloroform,
and acetone. The antifungal activity of these extracts was also performed
against Alternaria brassica, Alternaria braciola, Aspergillus Niger fungal
strain. The methanol and chloroform extracts show moderated as well as
significant activity against the strains.

In 2017 Deepa Srivastava, Department of Botany, D.D.U. Gorakhpur


University, Gorakhpur, UP, India published on Medicinal plant of genus
ipomoea: present scenario, challenges, and future prospective. The
members of the family Convolvulaceae are called "Morning Glories' ' as
they blossom to glory with the rising sun. The pleasing shape and the
variety of flower colors make morning glory an ideal and ornamental
plant for tropics and subtropics. The genus Ipomea contributes as the
largest genus of this family, having a wide range of economically
important plant species. The medicinal value of this genus is also
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noteworthy as many species are useful for the treatment of various
alignments such as constipation, inflammations, dysentery, rheumatism,
meningitis, diabetes, and hypertension This genus also shows
antibacterial, antimicrobial, antifungal, antiviral, and anticancer
activities. Bioactive compounds such as glycolipids, lignans, phenolic
compounds, and alkaloids are major constituents of this genus. This
work reviews the present scenario, challenges, and future perspective of
the genus for its medicinal value.

By reviewing the following literature, I have drawn the following


conclusions:

⮚ Ipomea hederacea is a member of the family Convolvulaceae, is


used mainly for its seeds, and is recognized for its medicinal
properties.

⮚ Many pharmacological properties such as diuretic, anti-diabetic,


anthelmintic, blood purifier, deobstruent, laxative, carminative and
anti-inflammatory actions have been described to this plant.

⮚ The plant possesses an overall antidiabetic activity.

⮚ Researchers have been carried out on anti-diabetic action on


ipomoeaspecies.

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⮚ The seed of this plant has also been used in both analgesic and
antiseptic properties.

⮚ No study to date has been conducted on the anti-diabetic action of


Ipomea hederacea seed.

Fig: Flowers of Ipomea hederacea

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Fig: Leaves of Ipomea hederacea

Fig: Seed of Ipomea hederacea

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Fig: Vine of Ipomea hederacea

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Fig: Stem of Ipomea hederacea

Fig: Buds of Ipomea hederacea

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OBJECTIVE OF THE STUDY

⮚ To perform extraction of seeds of Ipomea hederacea.

⮚ To perform different phytochemical assays, In vitro assays.

⮚ To investigate the antidiabetic effect of Ipomea hederacea seed against


diabetes-induced rats.

⮚ To perform differently in vitro assays for detection of antioxidant


activity.

⮚ To perform different biochemical assays of blood.

⮚ To perform histopathology of heart and kidney.

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PROPOSED PLAN FOR WORK

The main objective of the present study was to evaluate the antidiabetic action
of the methanolic extract of Ipomea hederacea.

Collection identification and authentication of plant species.

Isolation of the seed and grinding.

Extraction of active components by Maceration.

Perforation of phytochemical assays for qualitative identification of phytochemicals.

Perforation of different in vitro assays for detection of antioxidant activity.

Preclinical evaluation of extract in rats.

Biochemical analysis of different blood parameters.

Histopathology of heart and kidney for evaluation of protective action of the extract.

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MATERIAL AND METHODS

▪ COLLECTION OF PLANTS:

Ipomea hederacea Jacq. (kaladana or ivy leaf morning-glory), a member


of the family Convolvulaceae is used primarily for its seeds and
recognized for its medicinal properties, especially in Asian countries.
This medicinal herb contains various valuable chemical constituents
such as ecdysteroids, steroidal glycosides, aromatic acids, triterpenes,
amino acids, organic acids, mineral elements, and vitamins. Some
pharmacological properties such as diuretic, anthelmintic, blood
purifier, deobstruent, laxative, carminative and anti-inflammatory
actions have been ascribed to this plant, besides its use to treat
abdominal diseases, fevers, headache, and bronchitis. This review
focuses on the compositional, medicinal, and therapeutic properties of
this plant, as a potential source of bioactive molecules for medicinal and
nutraceutical applications.

▪ PREPARATION OF EXTRACT OF IPOMEA HEDERACEA:

The extraction of 500 g seed of IPOMEA HEDERACEA powder in


1000 ml of petroleum ether and distilled water according to their
increasing polarity. The extract was concentrated dried in a vacuum
(yield 8.8%) and residue stored in a refrigerator at 2-8°C for use in
subsequent experiments.

▪ EXPERIMENTAL ANIMALS:

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Male Wister rats weighing about 200-250 g were used for the study. All
animals were kept and maintained under laboratory conditions of
temperature (22 ± 2°C) and 12 h day:12 h night cycle as per guidelines
(CPCSEA, 2003). Animals were allowed free access to food (standard
pellet diet) and water ad libitum.

▪ CHEMICALS:

Methanol, Distilled water, Acetone, Diethyl ether, L-Ascorbic acid,


Sodium citrate, Sodium phosphate, Ethanol, Sodium carbonate,
Quercetin, Aluminium chloride, 1(M) Potassium acetate, Methanol,
Sodium hydroxide, α-naphthol, concentrated sulphuric acid,
Benedict’s reagent, Lead acetate solution, Wagner’s reagent,
Hager's reagent, Ferric chloride, the Chloroform solution
Streptozotocin, Nicotinamide, Metformin.

▪ INDUCTION OF DIABETES:

After 1 week of acclimatization, rats fasted overnight. Diabetes was


induced by a single intravenous (i.v) injection of streptozotocin 35
mg/kg dissolved in 0.1 M Citrate buffer (pH 4.5). After 48 hours of STZ
injection, fasting BGL has been checked and rats having BGL >250
mg/dl were considered as diabetic and taken into study.

▪ Experimental design and treatment schedule:

The diabetic rats were divided randomly into 5 groups consisting of 10


animals each. The group (I) was normal and received an equal volume
of physiological saline and 2% gum acacia.

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The group (II) of STZ induced rats received an equal volume of
physiological saline and 2% gum acacia was taken as diabetic control.
The group (III) of STZ induced rats received Metformin (10 mg/kg, p.o)
was taken as a reference standard. The group (IV) and (V) of STZ
induced rats received petroleum ether (250 mg/kg) and aqueous (250
mg/kg) extract of IPOMEA HEDERACEA for 18 days served as
treatment groups.

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