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��ࡱ�>��	�����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������[�	��k�bjbj����	|�ΐΐ�z�������UUUUU����iiii�
4i�%$A(iiii\r~3%5%5%5%5%5%5%$�'��*:Y%9U�X\��Y%UUii��%�!�!�!��UiUi3%�!�3%�!�!e#�#i������J��i8�}#%�%0�%�#,�*� ��*�#�#��*US$����!�����Y%Y%�!����%�������������������������������������������������������������������������*���������	:	Cinnamomumtamala :A POTENTIAL PROSPECT FOR NANOTHERAPEUTICS TO ELUCIDATE QUOTIDIAN DISORDERS
Upasana Saha, Purva Sudesh Dharwadkar, Yasrib Qurishi , Dr Shruti Awasthi*
Department of Life Sciences, Garden City University, Karnataka, India
*Corresponding Author: Garden City University, 16Th KM Old Madras Road Bangalore-560049
Email:  HYPERLINK "mailto:shruti.awasthi@gardencity.university" shruti.awasthi@gardencity.university ,  Tel : +91-9845689630

ABSTRACT
The world of nanoparticles is too small but yet too big. Plants of medical importance are being capitalized in synthesis of nanoparticles globally. One such plant species Cinamomumtamala still remains unexplored in the nano level its biomedical properties have been well studied but the nanoparticles are yet to be studied ( synthesized, characterized and implemented). Biomedical properties of  Cinamomumtamala has been studied but the contributors of these properties still remain untouched. Neither nanoparticles have been synthesized from this species nor the biomedical activities of  such nanoparticles has been explored. Hence this species remains a mysterious potential to the nano therapeutics which can tend to solve lots of increasing disorders in mere future if exploited at the nano level.
KEYWORDS: Diabetes, Flatulence, Nanotechnology, Green synthesis, Zinc oxide
INTRODUCTIONToday�s patients are entreating better health care, while the healthcare service providers searching for cost- effective treatments and diagnosis. Progress in the field of nanotechnology and its applications towards the field of biomedical industries and pharmaceuticals has revolutionized the twentieth century and provided benefits to the patients and the health care services. Nano-materials implement novel chemical and biological properties at a nanometer length scale (10-9 nm), and finds its direct application to biological targets. Applications of�nanoparticles�are expanding expeditiously on various fronts due to the enhancement of properties based on size, their distribution and morphology.
The world of nanoparticles is too small but yet too big. Utilizing�nano-materials�has enabled scientist to have a much better understanding of  biology. These small 10-9 sized particles have done wonders in the biomedical world. Nano-materials are synthetic or natural materials having less than 100 nm size in either of its direction. Technically any particle in having size in the nano-scale range can be classified as a nano-material, but their successful therapeutic applications have been found in the range of 10-100nm.
Globally, government currently spends about US$ 10 billion per year on nanotechnology research and development. By the end of 2011, the total government funding for nanotechnology research worldwide was more than US$ 65billion, which is expected to rise to US$ 100 billion in next few years. When figures for industry research and various other forms of private funding are taken into account, which were thought to have surpassed government funding figures as far back as 2004, it is nearly a quarter of a trillion dollars invested into nanotechnology by 2015. Nanotechnology is still a growing field but synthesis of nanoparticles is now even conducted at a global level on various plant and microbial species exploiting all possible plant parts which have some social, medical or economic importance. 
Nanotechnology uses numerous methods of synthesis to magnify the properties and reduce the production costs. Green synthesis of nanoparticles is an eco-friendly approach that employs plant extract with social, economic and biomedical importance. Significance of medicinal plants is not only confined to the narrow boundaries of therapeutic applications. Medicinally important plants are utilized to synthesize metal nanoparticles all over the world. Cinnamomumtamala is one of the medicinal plant species which is not explored at the nano level. The biomedical properties of this species have been well studied, but synthesis, characterization and implementation of nanoparticles are yet to be explored. The review focusses on the various possible applications of the unexplored species in the therapeutic world.



DIABETES: THE MOST DISCUSSED YET UNSOLVED DISORDER

The Disease: In the developing world diabetes is on hike. It is no longer an ailment of principally opulent nations, the ubiquity of diabetes is steadily expanding everywhere, most strikingly in the world�s middle-income countries. It is now one of the most indigenous diseases across the world and India being termed as the �Diabetic capital of the world� with as many as 50 million people enduring from type-2 diabetes; indeed has a defiance to face in the upcoming years. Diabetes mellitus (DM) also termed as simply diabetes is a collection of metabolic disordered characterized by high blood sugar levels over an extended time period. High blood sugar initiates symptoms like persistent urination, increased thirst and hunger. If left untreated, diabetes can cause many other severe complications, acute situations of which include diabetic ketoacidosis and non-kenotic hyperosmolar coma. Significant long-term complications also include heart disease, stroke, kidney failure, foot ulcers and retinal damage.Hyperglycemia produces the symptoms such as frequent urination, increased thirst, extreme hunger and unexplained weight loss.5% of young people were diagnosed with type 2 diabetes in the year 1994. Today, that number has risen to 40-50% in the present years. 
 Diabetes is caused due to deficit of insulin or resistance to insulin or both.
Type 1 Diabetes Mellitus emanates due to the body's failure to produce adequate insulin. This kind of disorder was previously termed as "insulin-dependent diabetes mellitus" (IDDM) or "juvenile diabetes". The cause of such condition is yet to be known. 
Type 2 Diabetes Mellitus embarks with insulin resistance, a state where cells fail to retort to produced insulin properly. As the disease advances a lack of insulin may also develop. This form of the disorder was previously referred to as "non-insulin-dependent diabetes mellitus" (NIDDM) or "adult-onset diabetes". The eminent cause of this condition is excessive body weight and lack of exercise.
Gestational Diabetes  is the third important form of diabetes and it occurs when pregnant women without a prior history of diabetes develop a high blood glucose level. 
Statistics : A common illusion states that diabetes is non-fatal; but WHO reckons deaths of 80% diabetics in low and middle-income countries and projects that such deaths will double between 2019 and 2030. WHO has predicted that diabetes will be the seventh leading cause of death in 2030. Not only in India, it is surmised that approximately 415 million people are diabetic worldwide which implies 1 out of 11 in the world's adult population suffer from this malady out of which 46% cases are undiagnosed. This figure is expected to soar up to 642 million people worldwide by 2040. Globally, an estimated of 422 million adults were living with diabetes in 2014, compared to 108 million in 1980. The global prevalence (age-standardized) of diabetes has nearly doubled since 1980, rising from 4.7% to 8.5% in the adult population. This reflects an increase in associated risk factors such as being overweight or obese. Over the past decade, diabetes prevalence has risen faster in low- and middle-income countries than in high-income countries.
Treatment and Prevention: Type - 1 diabetes cannot be controlled by oral medications. It can be treated through insulin injection or pancreases transplant to restore the proper amount of insulin in the body. Type - 2 diabetes is the major cause of premature deaths as the result actions need to be taken to prevent this condition. The factors that impact the lifestyle and dietary pattern need to be taken into consideration. Proper testing, treatment, lifestyle changes, eating pattern, exercise and physical activities have positive impact on the human health and controls type - 2 diabetes. However most of the type - 2 diabetics require oral medication but these patients gradually stop producing enough insulin and often stop the production, which ultimately leads to the need of insulin therapy along with the pills. Cigarette smoking and alcohol consumption should be avoided by the diabetic patients.
The lack of ingress to affordable insulin is a key hindrance to successful treatment and results in needless complications and premature deaths. The government is taking action towards the control of diabetes by planning to include higher taxes and stringent advertisement norms to regulate sale of sugar-sweetened beverages and junk�food.
FLATULENCE: A ROADBLOCK FOR GLOBAL FOOD LOVERS
Flatulence is an accumulation of  gas in the digestive system of the body excessive of which can give rise to abdominal discomfort and distress. It often occurs due of consumption certain variety of foods, but it can be a precursor sign of a more serious health conditions. When a person eat, drink or swallow saliva, they also engulf minimal amounts of air with it. This devoured air assembles in the gut. The gas within our digestive system mainly comprises of N2 and O2. During digestion process, gas, mainly in the form of H2, CH4, and CO2, is releaseds the gas builds up it may be categorized as follows: 
Upper Intestinal Gas: One of the most regular sources of upper intestinal gas is engulfed air. The biomedical synonym for swallowed air is aerophagia. It contains CO2, N2 and O2. Too much swallowed air lead to bloating and belching.
Lower Intestinal Gas: The breakdown of undigested foods in the large intestine by bacteria present leads to the accumulation of gas in the digestive system. The accumulated gas, made up of hydrogen, carbon dioxide, and in some people, methane, has nowhere to exit but is released out through the anus. The technical term for this gas is flatus. 
Control and treatment: There are several of ways to treat flatulence, depending on the cause of the problem.
Diet:�Cutting down on gassy foods, which include fruits like pears and apple, vegetables such as broccoli, Brussels sprouts, and onions; whole grains like bran, beans; and dairy products, including milk, cheese, and ice cream is necessary. These food items contain fiber, sugars, and starches that absorb easily, eventually leading to intestinal gas. We should consume five to six small meals in a day instead of three large meals to help improve the digestive process.
Chewing:� Habits such as smoking, chewing gum, and consuming water through increase the amount of air that you swallow. Fast eating makes a individual swallow more air, hence consume food at a slow pace.
Exercise:�Some people find that exercising helps to aid digestion and can avert flatulence.

EschericiaColiANDStaphylococcusaureus:THE TWO MAJOR CHALLENGES IN THE MICROBIAL WORLD

Escherichia coli�(abbreviated as�E. coli) are the type of bacteria present in the environment, contaminated water, raw food, and intestines of people and animals. This group of bacteria is large and diverse in nature. Most strains of E. coli are innocuous and are a part of healthy bacterial flora in the human gut. However, some types can provoke affliction in humans, including�diarrhea, abdominal pain,�fever, urinary tract infection and occasionally vomiting.75% to 95% of urinary tract infections are caused by E. coli.Some versions of E. coli particularly E. coli�O157: H7 can induce intestinal infection. E. coli�O157: H7 and other strains that engender intestinal sickness are called Shiga toxin� producing�E. coli�(STEC) due to the toxin that they produce. Intestinal infection symptoms include diarrhea,�abdominal pain,and fever and in severe cases can lead to�bloody diarrhea,�dehydration, or even�kidney failure.
Staphylococcus aureus�is�a major bacterial human pathogen�that leads to a wide�variety of clinical symptoms. Infections cause by Staphylococcus aureus�are difficult   to manage due to the advent of multi-drug resistant strains such as MRSA (Methicillin-Resistant�Staphylococcus aureus).�Staphylococcus aureus�are commonly found on the skin and 15% of the population constantly carries S.aureusin the anterior nares.About half of the adults are colonized by these bacteria. Mostly these bacteria do not cause an issue on the skin of the healthy individual; however it can turn deadly if the bacteria enter into the bloodstream and perfuse deeper into the body parts such as bone, lungs or heart. S. aureus�are one the most common bacterial infections in humans and can cause multiple human infections, including bacteremia, infective endocarditis, skin and soft tissue infections (e.g., impetigo, folliculitis, furuncles, carbuncles, cellulitis, scalded skin syndrome, and others), osteomyelitis, septic arthritis, prosthetic device infections, pulmonary infections (e.g., pneumonia and empyema), gastroenteritis, meningitis, toxic shock syndrome, and urinary tract infections.
Diseases caused by these bacteria are treated through various drugs but with the developing bacterial resistance the treatment and diagnosis are becoming challenging day by day. Hence alternative treatments for these bacteria are sought through nanotechnology.
NANOTECHNOLOGY: THE NEXT BIG THING IN THE BIOMEDICAL WORLD IS REALLY SMALL
Introduction to Nanotechnology and its importance in Therapeutics: Initially Nanotechnology was just an idea that most people simply didn�t believe. But today, impact of nanotechnology has exceeded the impact that electronics evolution has had in our lives. Scientifically, a particle in the nano-scale range can be classified as a nano-material, but their successful biomedical application has been noticed in the range of 10-100nm. In the upcoming years nanotechnology in medicine is expected to have a major impact in the survival of human race by making therapeutics easy to use and cost effective. The connection between nano-systems and biological systems is appearing as one of the broadest and most potent areas of science and technology that blend together biology, chemistry, physics and many areas of engineering, biotechnology and medicine. Nanoparticles have budding applications in the field of therapeutics. Drugs can be administrated with better safety profile by utilizing the nanoparticles. Nanotechnology aims at developing new material to treat diseases in a targeted, accurate, effective and enduring way, with the ultimate goal of making medical practice safer and fewer invasions.
Government contributions in the field: Globally, governments currently spend about US$ 10 billion per year on nanotechnology research and development. By the end of 2011, the total government funding for nanotechnology research worldwide was more than US$ 65 billion, which is expected to rise to US$ 100 billion in next few years. When figures for industry research and various other forms of private funding are taken into account, which were thought to have surpassed government funding figures as far back as 2004, it is nearly a quarter of a trillion dollars invested into nanotechnology by 2015. Nanotechnology is still a growing field but synthesis of nanoparticles is now even conducted at a global level on various plant and microbial species exploiting all possible plant parts which have some social, medical or economic importance. 
Not only abroad, the government has played a pioneering role in promoting nanotechnology R&D in India. It has taken many initiatives to foster R&D in India through the efforts of several departments. Many schemes/programs have been launched for infrastructure and human resource development. The government has also undertaken many bilateral/multilateral/regional initiatives with many countries to promote nanotechnology research, development and innovation (RDI). It has also encouraged PPP model to encourage nano-based product development. The US government provides notable funding for nanotechnology research and development through the National Nanotechnology Initiative (NNI), as well as individual federal agencies. 

               The NNI focuses on the establishment of more than 60 nanotechnology research and education centres which provides the facilities to users by sparing them the cost of purchasing high price equipments required for the research in nanotechnology, thereby  encouragingthe development and characterization of new nonmaterial�s. In the year 1985-1997 the government provided US$452 million to support projects related to nanotechnology.
             With the support from the government and different funding agencies research with nanoparticles have flourished well in India. Maximum research till date has been conducted with synthesis of silver nanoparticles from different medicinal plants and microbes. While gold, zinc oxide and iron nanoparticles also contribute to nano-technological research but they have been less explored.

GREEN SYNTHESIS OF NANOPARTICLES: A COMBINATION OF NANOTECHNOLOGY AND THE HERBAL WORLD

       Nanotechnology is the application of biomedical science to control the problem at molecular level. Nano-particles are of great importance due to their small size and large surface to area volume .The biosynthesis processes for the synthesis of nanoparticles is becoming increasingly popular and is much needed to solve the problems associated with environmental concerns worldwide. The biosynthesis of�nanoparticles�has been proposed as cost-effective and eco- friendly replacement to chemical and physical methods Production of metal nanoparticles using organism is one of the most considered method. Plants and plant extracts are the best alternatives for the synthesis of nanoparticles at the large scale. Plants are considered as chemical factories of the nature as they are cost effective and require low maintenance. Nanoparticles produced by plants can be synthesized at a faster rate and provides more control over the size and the shape of the nanoparticles synthesized. The advantages of using plant and plant - extracts for biosynthesis of metal nanoparticles have made the researchers curious to investigate mechanisms of metal ions uptake and bio reduction by plants, and to understand the possible mechanism of metal nanoparticle formation in plants.
NANOTECHNOLOGY BASED SOLUTIONS FOR DIABETES AND FLATULENCE
Nanotechnology and its development has been a boon to mankind and a blessing for the diabetics by facilitating the development of novel glucose measurement tools, devices and techniques for insulin delivery which promise to drastically trump the quality of life for the diabetics. For example, the refined glucose sensor technology has an instant and remarkable impact on their health, as improved and quick sensing will help more accurate insulin dosing and hence in turn in diabetes management. Indeed, flourishing nano - medicine has already accelerated novel sensors capable of more frequent and convenient blood glucose measurements. 
Nano-medicine has also entitled more sturdy insulin delivery systems to maintain normoglycemia. Such systems constitute a massive advancement over contemporary standards of care. The clinical application of these technologies will allow diabetics to manage their disease more effectively and improve their health and quality of life. Though Nanotechnology has contributed towards diabetes, the flatulence field still remains unexplored at the nano-scale. For this disease the applications have been found only as a drug delivery system. A proper nano-product for flatulence is still to be formulated.
ZINC OXIDE (ZnO) NANOPARTICLES: LESS EXPLORED BUT MORE IMPORTANT
�Zinc oxide (ZnO) is an inorganic compound which has widely found its applications in the world of nanotechnology. ZnO nanoparticles are currently labeled as a �generally recognized as safe� (GRAS) material by the FDA. With the emergence of nanotechnology the development of ZnO materials with new properties for use as antimicrobial agents has been discovered. Thus, ZnO in nano-scale has shown prospective applications in designing antimicrobial agents. 
Studies have also been conducted to check anti-diabetic property of  ZnONPs and results showed a great demolition in blood glucose level in diabetic groups treated with ZnONPs (75.8%).In another study oral imposition of zinc oxide nanoparticles resulted in notable anti-diabetic effects higher serum insulin (70%), reduced blood glucose (29%), reduced non esterified fatty acids (40%) and reduced triglycerides (48%). Nanoparticles were comprehensively absorbed resulting in upraised zinc levels in the liver, adipose tissue and pancreas. These Nanoparticles were found safe up to a 300 mg/kg dose in rats.
Cinnamomumtamala: A POTENTIAL PLANT; YET TO BE EXPLORED AT THE NANO LEVEL
The plant and its uses: C. tamala, commonly known as Tejpatta or Indian Bay leaf is a tree that belongs to� HYPERLINK "https://en.wikipedia.org/wiki/Lauraceae" \o "Lauraceae" Lauraceae�family that is native to India, Bangladesh, Nepal, Bhutan, and China .Extract of�C. tamala�leaves administrated to the strepozotocin � induced diabetic rats restored, lowered, maintained body weight and lipid profile to normal range. Bay leaves also aid in digestion and can medicate digestive disorders such as heartburn and flatulence. Bay leaf concoction can treat digestive disorders like constipation, acid reflux and irregular bowel movements. 
The unexplored Nano-world of the species: The present studies and investigation reveal the huge potential of bay leaf against some specific bacteria, as well as antidiabetic and a carminative agent. Several studies have been conducted on these species to explore its biomedical properties. In one such study, extract of C. tamala leaves were fed at 10 mg/kg to alloxan -induced diabetic rats for 15 days and at the end of the experiment significant reduction in blood glucose level was found in the diabetic rats, blood glycosylated hemoglobin, LPO, serum AST, and ALT, and significant elevation in the antioxidant enzymes such as CAT, GSH, and SOD. From the conclusion of these studies C. tamala was proved to be a great contributor towards adjunct therapy in diabetes. These species are also superior for digestion treatment like heartburn and flatulence. But the studies are not carried out at the nano level. Various biomedical properties of Cinnamomumtamala has been studied in vitro like its anti-diabetic property, anti-flatulence property etc. But the contributors of these properties still remain untouched. Neither zinc oxide nanoparticles have been synthesized from this species nor the biomedical activities of such nanoparticles has been explored. Due to the conducted research the necessity of the studies of ZnO Nanoparticles of this species becomes a prior importance as this plants can provide solutions to the most critical diseases very easily when exploited at the nano level.
CONCLUSION
Nanotechnology has prominently emerged as one of the most dominant engineering approaches in the past half century. Nanotechnology introduced nanomaterials in the field of biomedical science with variegated applications. 
Diabetes is be one of the most discussed about disorder across the world and especially in India, but concognizance about the same can well be approximated by the fact that India has more people with diabetes mellitus�than any other sovereign. The second severe problem faced by food loving Indian society is gastric or flatulence issue. Diabetes and flatulence in India has become a challenge to treat without medications. Herbal treatment of these disorders is yet to be formulated. The present investigations show enormous potential of Indian bay leaf spices against some specific bacteria as well as an antidiabetic and a carminative agent. The species have not been studied at the nano level. Since the nano world has proved to be miraculous to the biomedical world; a trial has been made through this project to exploit the nanoparticles from these species and test their potential activity against some bacteria and also to fight diabetes and flatulence.As the global scenario is now changing towards the use of nontoxic plant products having traditional medicinal use, development of products from medicinal plants should be emphasized for the control of various diseases especially growing conditions like diabetes and flatulence.
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