Herbal drugs and herbal mediated silver nano particles as anti diabetics: A new horizon

Abstract

Diabetes is a chronic metabolic disorder that affects millions of people worldwide and takes a heavy toll on human life. Traditional plant treatments have been used throughout the world for the therapy of diabetes mellitus. Among several medications and other alternative medicines, herbal drugs have been known to cure and control diabetes; additionally they have no side effects. Newer drugs with the least side effects but with highest efficiency are being relentlessly searched by the researchers. Herbal drugs are very common in use in our day to day life easily available and are having least side effects. Nanotechnology is a branch of science and technology conducted at the nanoscale, which is about 1 to 100 nanometers. Nanoscience and nanotechnology are having a wide range of applications in fields, such as green chemistry, herbal drug research. With respect to herbal medicine the drug will take more time to show the anti diabetic activity because herbal drugs are basically more insoluble in nature. To overcome this kind of problems nano herbal medicine is needed. Herbal mediated silver nanoparticles (HMSNP’s) are having less particle size, more surface area, more solubility which results in the optimum dose of drug that can reach to systemic circulation and onsite of action is very quick. Recent studies on the use of herbal plant extracts in synthesis of HMSNP’s are a relatively new and exciting area of research with considerable potential for development of new methods in nano medicine. HMSNP’s capable to treat diabetes effectively by having very less particle size comparatively with herbal medicine current review is an attempt to list of out the anti diabetic plants, biosynthesis and various characterization methods of HMSNP’s and their advanced pharmacological applications to treat diabetes.

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Int. J. Pharm. Sci. Rev. Res., 31(2), March – April 2015; Article No. 24, Pages: 142-148 ISSN 0976 – 044X
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Shanker Kalakotla*, Krishna Mohan Gottumukkala, Sandhya Rani M, Pravallika P L
Centre for Pharmaceutical Sciences, Inst of Science and Technology, JNT University Hyderabad, Kukatpally, Telangana, India.
*Corresponding author’s E-mail: shankerkalakotla@gmail.com
Accepted on: 12-02-2015; Finalized on: 31-03-2015.
ABSTRACT
Diabetes is a chronic metabolic disorder that affects millions of people worldwide and takes a heavy toll on human life. Traditional
plant treatments have been used throughout the world for the therapy of diabetes mellitus. Among several medications and other
alternative medicines, herbal drugs have been known to cure and control diabetes; additionally they have no side effects. Newer
drugs with the least side effects but with highest efficiency are being relentlessly searched by the researchers. Herbal drugs are very
common in use in our day to day life easily available and are having least side effects. Nanotechnology is a branch of science and
technology conducted at the nanoscale, which is about 1 to 100 nanometers. Nanoscience and nanotechnology are having a wide
range of applications in fields, such as green chemistry, herbal drug research. With respect to herbal medicine the drug will take
more time to show the anti diabetic activity because herbal drugs are basically more insoluble in nature. To overcome this kind of
problems nano herbal medicine is needed. Herbal mediated silver nanoparticles (HMSNP’s) are having less particle size, more
surface area, more solubility which results in the optimum dose of drug that can reach to systemic circulation and onsite of action is
very quick. Recent studies on the use of herbal plant extracts in synthesis of HMSNP’s are a relatively new and exciting area of
research with considerable potential for development of new methods in nano medicine. HMSNP’s capable to treat diabetes
effectively by having very less particle size comparatively with herbal medicine current review is an attempt to list of out the anti
diabetic plants, biosynthesis and various characterization methods of HMSNP’s and their advanced pharmacological applications to
treat diabetes.
Keywords: Herbal drugs, Herbal mediated Silver Nanoparticles (HMSNP’s), Diabetes mellitus, Optimum dose, Nanoscience and
Nanotechnology.
INTRODUCTION
iabetes is a metabolic disorder; it is mainly caused
by dysfunction of the β cells of the pancreas. This
in turn leads to decreased production of the
hormone insulin and/or increased resistance to the action
of insulin in the peripheral tissues1. Diabetes can be
categorized into two types: type 1 and type 2. Type 1
Diabetes or juvenile-onset diabetes develops when the
body’s errant immune system damages and destroys the
pancreatic β cells that produce the blood glucose
regulating hormone insulin.
To survive with type 1 diabetes must need to have an
exogenous delivery of insulin hormone. This form of
diabetes usually attacks children and young adults,
although the onset of the disease may occur at any age2.
In adults, type 1 diabetes accounts for about 5% of all
diagnosed cases of diabetes. Risk factors for type 1
diabetes may be autoimmune, genetic or environmental.
Till now there is no known way to prevent type 1 diabetes
exists. Several clinical trials for preventing type 1 diabetes
are being planned or currently in progress3.
Type-2 diabetes (non-insulin-dependent diabetes
mellitus; NIDDM) or adult-onset diabetes usually begins
as a progressive insulin resistance/insensitiveness, with
an ensuing reduction in the ability of the pancreatic
hormone to promote peripheral glucose disposal and to
suppress hepatic glucose output4. The pancreas pumps
out increasing amounts of insulin to normalize blood
glucose levels as compensation.
Over time, as long as a decade, this ever increasing
production becomes unsustainable and the pancreas’
ability to produce insulin declines.
As a result, the level of blood glucose rises as a result it
begins to appear in the urine and causes increased
urination. Established risk factors for type 2 diabetes
include genetic polymorphism, family history, physical
inactivity, obesity, older age and stress5.
Type 2 Diabetes Mellitus affected individuals need to
follow a diet and perfect exercise programs to control the
blood glucose levels. If this first line treatment does not
control blood sugar levels effectively, an oral medication
can be preferable to the treatment plan. In certain
circumstances, patients with type 2 diabetes may also
require insulin in the form of injection.
Moreover many patients need to control their blood
pressure and cholesterol levels.
Type 2 diabetes accounts for about 90% to 95% of all
diagnosed cases of diabetes. African Americans,
Hispanic/Latino Americans, American Indians and some
Asian Americans are at particularly high risk for type 2
diabetes, along with its complications, and are also being
diagnosed, although still rare, as children and
adolescents.
Herbal Drugs and Herbal Mediated Silver Nano Particles as Anti Diabetics: A New Horizon
D
Research
Article

Int. J. Pharm. Sci. Rev. Res., 31(2), March – April 2015; Article No. 24, Pages: 142-148 ISSN 0976 – 044X
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143
Figure 1(A):
Pathophysiology- Diabetes
mellitus
Figure 1(B) Glucose
Regulation by Insulin
hormone
What is Nanotechnology?
Nanotechnology is defined as the “intentional design,
characterization and production of materials, structures
and systems by controlling their size and shape in the
nanoscale range 1 to 100 nm 6-7”. As the nano particles
are similar in scale to biological molecules and systems
yet can be engineered to have various functions,
nanotechnology is potentially useful for medical
applications. The field of nanomedicine aims to use the
properties and physical characteristics of nanomaterials
for the treatment of diseases at the molecular level.
The field of nanotechnology is one of the upcoming areas
of research in the modern field of material science.
Nanoparticles show completely new or improved
properties, such as size, distribution and morphology of
the particles etc. Novel applications of nanoparticles and
nanomaterials are emerging rapidly in various research
areas such as Pharmacy and medicine etc.8
Why Nanoparticles unique from normal size particles?
Nanoparticles have a high specific surface area and
unique properties of size and shape. Because of the
unique physicochemical characteristics of nanoparticles,
including anti cancer, anti diabetic, antibacterial
properties and magnetic properties9-11 they are gaining
the interest of researchers for novel methods of
synthesis. From the past decade, the synthesis of metal
nanoparticles is been a most important topic of research
in modern material science and medicine nano
technology. Nano-crystalline silver particles have been
providing applications in the fields of high sensitivity
biomolecular detection, diagnostics, antimicrobials,
therapeutics. However, there is still need for economical
and easily available and clean synthesis route to
synthesize the silver nanoparticles. Silver is well known to
possess an inhibitory effect toward many bacterial strains
and microorganisms commonly present in medical and
industrial processes12. In medicines, silver and silver
nanoparticles have an ample of applications including skin
ointments and cream which containing silver to prevent
infection of burns and open wounds13, medical devices
and implants prepared with silver-impregnated
polymers14. In textile industry, silver-embedded fabrics
are now used in sporting equipment 15. According to
present research scenario especially the silver nano
particles have been playing an important role in Herbal
nano technology to prevent chronic diseases like diabetes
and cancer etc.
Table 1: Medicinally Active Plants with Antidiabetic and
Related Beneficial Properties
Botanical name Family Activity reported
Beta vulgaris L. Beta vulgaris L. Increases glucose tolerance in
OGTT16
Bombax ceiba L. Malvaceae Hypoglycemic17
Butea manosperma Cesalpinaceae Anti-hyperglycemic18
Cynodon dactylon Poaceae Anti-hyperglycemic19
Eriobotrya japonica Rosaceae Hypoglycemic20
Gentiana olivieri L. Gentianaceae Hypoglycemic, anti-
hyperlipidemic21
Globularia alypum L. Globulariaceae Hypoglycemic22
Glycyrrhiza uralensis Papil ionaceae Decreases the blood glucose
levels23
Morus indica. L. Moracea Hypoglycemic24-25
Morus inignis L. Moraceae Hypoglycemic26
Murraya koenigii L. Rutaceae Hypoglycemic, increases
glycogenesis27
Nigella saliva Ranunculaceae Hypoglycemic28
Ocimum gratissinuim Lami aceae Hypoglycemic29
Pandanus odorus Pandanaceae Hypoglycemic30
Parmentieru edulis Bignoniaceae Hypoglycemic31
Phyllanthus sellowianus. Euphorbiaceae Hypoglycemic32
Psacalium decompositum Asteraceae Hypoglycemic33
Psacalium peltatum Asteraceae Hypoglycemic34
Tinospora crispa Menispermaceae Hypoglycemic 35
Urtica dioica Urticaceae Hypoglycemic 36
Urtica pilulifera L. Urticaceae Hypoglycemic37
Vinca rosea L. Apocynaceae Hypoglycemic38
Withania somnifera Solanaceae Hypoglycemic, antioxidant39-40
Why Silver?
Silver is one of the basic interesting elements with
peculiar properties in the multidisciplinary fields of
research. It is a naturally occurring element, slightly
harder than gold and very ductile and malleable. Pure
silver has the highest electrical and thermal conductivity
of all metals and has the lowest contact resistance. Silver
can be present in four different oxidation states: Ag0,
Ag2+, Ag3+. The former two are the most abundant ones,
the latter are unstable in the aquatic environment41.
Metallic silver itself is insoluble in water, but metallic salts
such as AgNO3 and Silver chloride are soluble in water
(WHO, 2002). Metallic silver is used for the surgical
prosthesis and splints, fungicides and coinage. Soluble

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silver compounds such as silver slats, have been used in
treating mental illness, epilepsy, nicotine addition,
gastroenteritis and infectious diseases including syphilis
and gonorrhea. Although acute toxicity of silver in the
environment is dependent on the availability of free silver
ions, investigations have shown that these concentrations
of Ag+ ions are too low to lead toxicity (WHO, 2002).
Metallic silver appears to pose minimal risk to health,
whereas soluble silver compounds are more readily
absorbed and have the potential to produce adverse
effects42. The wide variety of uses of silver allows
exposure through various routes of entry into the body.
Ingestion is the primary route for entry for silver
compounds and colloidal silver proteins. Dietary intake of
silver is estimated at 70-90µg/day, since silver in any form
is not expected to be toxic to the immune, cardiovascular,
nervous or reproductive system and it is not considered
to be carcinogenic43, hence silver is relatively non-toxic44.
Silver demand will likely to rise as it finds new
applications, particularly in medical, textiles and plastics
fields, changing the pattern of silver emission as these
technologies and products diffuse through the global
economy.
Traditional system of medicine in Nanotechnology
Traditional system of medicine such as Ayurveda can
serve as an excellent tool for human in nanomedicine
category. A research work shows that traditional
medicines such as Ayurveda Bhasma may hold strong
relevance in the emerging area of nanomedicine. The
purposeful advantage emerges if the traditional system of
medicine combines with metal-based nanomedicine45.
Recent study reveals that Ayurvedic Bhasma are alike the
nanocrystalline material. This serves the usage of Bhasma
as targeted drug delivery, the reason behind they are
biocompatible and non-toxic46-47.
Synthesis of HMSNP’s
Nanoparticles can be synthesized using various
approaches including chemical, physical, and biological.
Although chemical method of synthesis requires short
period of time for synthesis of large quantity of
nanoparticles, this method requires capping agents for
size stabilization of the nanoparticles. Chemicals used for
nanoparticles synthesis and stabilization are toxic and
lead to non-eco friendly by products. The need for
environmental non-toxic synthetic protocols for
nanoparticles synthesis leads to the improving interest in
biological approaches which are free from the use of toxic
chemicals as byproducts. Thus, “green nanotechnology”
has an increasing demand48. Many biological approaches
for both extracellular and intracellular nanoparticles
synthesis have been reported till date using
microorganisms including bacteria, fungi and plants49,50.
Plants provide better results for nanoparticles synthesis
as they are free from toxic chemicals as well as provide
natural capping agents. Moreover, use of plant extracts
also reduces the cost of microorganism’s isolation and
culture media enhancing the cost competitive feasibility
over nanoparticles synthesis by microorganisms51.
Sometimes the synthesis of nanoparticles using various
plants and their extracts can be advantageous over other
biological synthesis processes which involve the very
complex procedures of maintaining microbial cultures52-
53. Many such experiments have already been started
such as the synthesis of various metal nanoparticles using
fungi like Fusarium oxysporum54, Penicillium species55 and
using some bacteria such as Bacillus subtilis etc.56, 57. But,
synthesis of nanoparticles using plant extracts is the most
adopted method of green, eco-friendly production of
nanoparticles and to handle and act as a source of several
metabolites58. There has also been several experiments
performed on the synthesis of silver nanoparticles using
medicinal plants such as Oryza sativa, Helianthus annus,
Saccharum officinarum, Sorghum bicolour, Zea mays,
Basella alba, Aloe vera Capsicum annuum, Magnolia
kobus, Medicago sativa (Alfalfa), Cinamomum camphora
and Geranium species in the field of pharmaceutical
applications and biological industries. Besides, green
synthesis of silver nanoparticles using a methanolic
extract of Eucalyptus hybrida was also investigated59. In
the recent days, silver nanoparticles have been
synthesized from the naturally occurring sources and
their products like green tea (Camellia sinensis), Neem
(Azadirachta indica), various leaf broth, natural rubber,
starch, Aloe vera plant extract, lemon grass leaves
extract, etc.60.
Green synthesis of Silver nano particle
Silver nanoparticles
The major advantage of using plant extracts for silver
nanoparticle synthesis is that they are easily available,
safe, and nontoxic in most cases, have a broad variety of
metabolites that can aid in the reduction of silver ions.

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The main mechanism considered for the process is plant-
assisted reduction due to phytochemicals. The main
phytochemicals involved are terpenoids, flavones,
ketones, aldehydes, amides, and carboxylic acids.
Flavones, organic acids, and quinones are water-soluble
phytochemicals that are responsible for the immediate
reduction of the ions. Studies have revealed that
xerophytes contain emodin, an anthraquinone that
undergoes tautomerization, leading to the formation of
the silver nanoparticles. In the case of mesophytes, it was
found that they contain three types of benzoquinones:
cyperoquinone, dietchequinone, and remirin. It was
suggested that the phytochemicals are involved directly
in the reduction of the ions and formation of silver
nanoparticles61.
Figure (2A, 2B): AFM images of silver nanoparticles
Figure 2C: TEM image of silver nanoparticles
Need for Green Synthesis
Biosynthesis of nanoparticles is a kind of bottom up
approach where the reduction/oxidation is the main
occurring reaction. The need for biosynthesis of
nanoparticles rose as the physical and chemical processes
were costly. Often, chemical synthesis method leads to
presence of some of the toxic chemical absorbed on the
surface that may have adverse effect in the medical
applications62. This is not an issue when it comes to
biosynthesized nanoparticles via green synthesis route63.
So, in the search of economic pathways for nanoparticles
synthesis, scientist used microbial enzymes and plant
extracts (phytoconstituents). With their antioxidant or
reducing properties they are usually responsible for the
reduction of metal compounds into their respective
nanoparticles. Green synthesis provides advancement
over chemical and physical method as it is cost effective,
environment friendly, easily scaled up for large scale
synthesis and in this method there is no need to use high
pressure, energy, temperature and toxic chemicals.
Applications of Silver Nanoparticles
Nanoparticles are of great interest due to their extremely
small size and large surface to volume ratio, which leads
to both chemical and physical differences in their
properties compared to bulk of the same chemical
composition, such as mechanical, biological and sterical
properties, catalytic activity, thermal and electrical
conductivity, optical absorption and melting point64.
Hence, designing and production of materials with novel
applications can be results by controlling shape and size
at nanometer scale. Nanoparticles exhibit size and shape-
dependent properties which are of interest for
applications ranging from biosensing and catalysts to
optics, antimicrobial activity, computer transistors,
electrometers, chemical sensors, and wireless electronic
logic and memory schemes. These particles also have
many applications in different fields such as medical
imaging, nano-composites, filters, drug delivery, and
hyperthermia of tumors65-66. Silver nanoparticles have
drawn the attention of researchers because of their
extensive applications in areas such as integrated
circuits67, sensors, biolabelling, antimicrobial deodorant
fibres68, low-cost paper batteries (silver nano-wires)69 and
antimicrobials70. Silver nanoparticles have been used
extensively as antimicrobial agents in health industry,
food storage, textile coatings and a number of
environmental applications. In general, therapeutic
effects of silver particles (in suspension form) depend on
important aspects, including particle size (surface area
and energy), particle shape (catalytic activity), particle
concentration (therapeutic index) and particle charge71.
Pharmacological applications of HMSNPs
Can Nanotechnology bring relief to Diabetics? Beneficial
Role of Nano Herbal Medicine
Several instances of earlier studies reported many
possibilities of nanotechnology to implement new ways
of treating diabetes.
As the world population increases, improved resources
are needed to sustain society. An alternative to this issue
is to be highly efficient and this could be achieved
through nano science and technology. With this new
technology, diabetics may become completely free from
dietary regulations and the restrictive systematic regime.

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Some devices are so adjustable that diabetics will no
longer be dependent on insulin injections and their blood
glucose levels will be adjusted according to their glucose
level at that moment in time. This would enable them to
lead a normal life, especially the young who are always
active. It helps the patient to feel more mentally
secure/better and confident, as well as being cost-
effective in other aspects as it requires fewer resources
with a much more effective outcome. Efficiency is
essential as the world population increases, hence
economic efficiency is the most stable way of supporting
the billions of people all over the world with diabetes.
CONCLUSION
Herbal mediated silver nanoparticles: Scope of Future
Research
A literature survey of current topic suggests that a lot of
work has been undertaken to establish the anti-diabetic
potentials of several drugs, ranging from homeopathy
and Ayurvedic to formulated nano medicines yet the field
of nanotechnology or nanomedicine needs special
attention. In this context, there is an open era of research
to establish standard nano drugs and to explore more
advanced insulin therapy, their nano formulations,
delivery and the pathway through which they act. Finding
the truth of which drugs are really capable of bringing
about corrective modulations of some parameters at
molecular level and are scientifically acceptable with
protocols/methodologies adopted that can be repeated
by others is absolutely mandatory. Exploring this area of
research will not only bring a new dimension in the
regimen of treatment to diabetic patients, but should also
be a step forward towards building a platform for
development of newer scientifically tested drugs by
following an advanced procedure of drug designing.
The discovery and development of potent antidiabetic
drugs have been significantly hampered due to a lack of
suitable preclinical models with respect to the optimum
dose of the drugs to check the efficacy of candidate
agents. To bridge the gap, these drugs should include the
kingdom of natural products (KNP), but at the same time
need to show enhanced bio availability, target-specific in
action and utilize the different aspects of
nanotechnology. Synthesized and formulated herbal
mediated silver nanoparticles not only biodegradable,
biocompatible and non-toxic but also would have a
greater ability to enter biological cell membrane and
show more quick action thereby providing great bio
availability as an alternative system of herbal medicine to
treat diabetes.
Acknowledgement: Authors sincerely acknowledge SERB-
Science and Engineering Research Board DST-New Delhi,
for providing financial support to carry out the work. I
thank HOD CPS, IST, JNT University Hyderabad for
providing necessary facilities.
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Source of Support: Nil, Conflict of Interest: None.