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Anti-Obesity Drug Discovery and Development

Volume 4

by

Prof. Dr. Atta-ur-Rahman, Prof. Dr. M. Iqbal Choudhary

eISBN: 978-1-68108-558-6, 2018
ISBN: 978-1-68108-559-3
ISSN: 2467-9615 (Print)
ISSN: 2210-2698 (Online)



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Obesity is a complex health problem, caused by a number of factors such as excessive food intake, lack of physical activity, genetic p...[view complete introduction]

Preface

Obesity disorders are on the rise globally, and have reached to epidemic proportions in certain regions of the world. Obesity is regarded as the mother of many illnesses, as it increase the chances of onset of conditions, such as cardiovascular diseases, diabetes, certain cancers, chronic kidney diseases, gallbladder stones, osteoarthritis, gout, respiratory problems, as well as psychological disorders and social isolation. Therefore, treatment of obesity by life style modifications, chemotherapy, and surgery has multiple benefits by causing reduction of many diseases. Unfortunately, the aetiology of obesity is extremely complex, and it is equally difficult to treat. It is not just the consumption of extra calories or lack of physical activities that causes obesity, there are many other complex underlying causes.

The treatment of obesity often requires a personalized approach. Current therapies for obesity and weight reduction are associated with severe after effects, creating the need for extensive research in obesity prevention and treatment. Drugs which are safe and effective are urgently required not only to treat obesity, but also to prevent and treat associated disorders. Extensive work in this field has also created a niche for authoritative reviews on the topic. The current book series is an attempt to fulfil this need.

The first three volumes of the ebook series “Anti-Obesity Drug Discovery and Development” have been very well received as very useful additions to the global literature in this dynamic area of research. Volume 4 is also a humble effort to continue this scholarly tradition. The 4th volume of this widely recognized book series comprises six invited reviews on various aspects of anti-obesity drug discovery and treatment of obesity related diseases, and they have been contributed by leading experts in this field. Each of these reviews is focused on drug discovery and development against obesity and related disorders, including new knowledge of molecular and cellular basis of obesity diseases, rationale for multi-target approach, outcomes of pre-clinical and clinical studies on new anti-obesity drugs and drug delivery systems, and potential of natural products in obesity treatment. Each chapter addresses a different aspect of the topic, and comprehensively reviews the state of the art, both in terms of understanding of the disease, as well as the therapeutic interventions developed so far.

The first review contributed by Wan and Kwan starts with a commentary on the relationship between diet and obesity, and the onset of various cancers. A comprehensive write-up on the role of dietary modulations in the prevention and treatment of cancer is presented. Diets rich in omega-3 polyunsaturated fatty acids, fiber, anti-oxidants, including polyphenols are known to reduce the chances of obesity and cancer. Some of them are anti-angiogenic which prevent the progression of cancer, especially solid tumors. However, it is often difficult to generalize the dietary recommendations, as individuals may have different life styles, gut microbiota, metabolic rates, as well as genetic make-up. Based on this, the authors have also introduced the interesting concept of “personalized nutrition”, as one size doesn’t fit all. In order to design personalized nutrition, system biology approach, and “omic” techniques can be employed.

Polycystic ovary syndrome (POCS) is among the most common endocrine disorders in women of reproductive age, leading to a whole range of problems, including infertility, metabolic and psychological problems. POCS is highly prevalent in obese females (40% -60%), and thus obesity is regarded as one of the risk factors for POCS. Weight loss through life style changes is the first-line treatment in overweight PCOS women. Insulin-sensitizing drugs such as metformin, glucagon-like peptide-1, and antiobesity drugs such as Orlistat are used. Turkcuoglu and Melekoglu present a comprehensive review on the role of anti-obesity medications in the prevention of a common health disorder polycystic ovary syndrome (POCS).

Rolo et al. review the role of mitochondrial dysfunction in obesity. Mitochondria play a crucial role in energy metabolism. Extreme events during obesity disorders, such as chronic inflammation, oxidative stress, increased nutrient supply, etc. lead to mitochondrial dysfunctions. The authors discuss how restoration of mitochondrial health can contribute to the prevention and treatment of obesity. They highlight emerging interventions which can help in boosting mitochondrial activity and repair mitochondrial damage.

Orlistat is one of the most widely used drugs for the treatment of obesity. It functions by preventing the absorption of fats from the human diet through lipase inhibition, and thus reduces caloric intake. However Orlistat is notorious for its gastrointestinal side effects, including steatorrhea or oily, loose stools. Sunil K. Jain has reviewed recently developed new formulations of Orlistat which can reduce the associated side effects of this useful drug. These include calcium silicate based floating microspheres, and floating granules. Merits and demerits as well as safety profiles of these drug delivery systems have been comprehensively reviewed.

The chapter contributed by Lakshmi and Thiyagarajan is primarily focused on a multi-targeted approach towards the treatment of obesity disorder. Various mechanisms are involved in the on-set and progression of obesity. Based on this approach, multi-target drugs are needed for the successful treatment of obesity. Examples of such agents include glucagon-like peptides-1 mimetics and insulin secretagogues reported for anti-obesity activity. Natural products, mostly obtained from medicinal plants, can exhibit multi-targeted action, due to their diverse and complex structures. Some of these natural products, such as polyphenols, alkaloids, sterols, glycosides, terpenes, saponins, etc can work through diverse mechanisms, such as appetite suppression, metabolic enzyme inhibitions, increased insulin secretion, etc, all relevant to obesity control.

Augustine et al. have focussed on plant-based anti-obesity drugs in the next chapter. The authors have presented a comprehensive review on anti-obesity properties of several plant species, along with the known mechanisms of action. The review provides a strong rationale of the need of further research on the use of medicinal plants, particularly those used in traditional systems of medicine, as safe and effective anti-obesity agents.

We would like to express our sincere thanks to all the contributors for their excellent scholarly works. We also appreciate efforts of the efficient team of Bentham Science Publishers for the timely publication of the 4th volume of the book series. The organizational and communication skills of Ms. Faryal Sami (Manager Publications), Mr. Shehzad Naqvi (Editorial Manager Publications) and the excellent management of Mr. Mahmood Alam (Director Publications) are also gratefully acknowledged. We sincerely hope that the volume will provide readers with a better understanding of the subject, and motivate them to conduct good quality research on obesity.

Atta-ur-Rahman, FRS
Honorary Life Fellow
Kings College
University of Cambridge
Cambridge
UK

&

M. Iqbal Choudhary
H.E.J. Research Institute of Chemistry
International Center for Chemical and Biological Sciences
University of Karachi
Karachi
Pakistan

List of Contributors

Editor(s):
Prof. Dr. Atta-ur-Rahman
Honorary Life Fellow
Kings College
University of Cambridge
Cambridge
UK


Prof. Dr. M. Iqbal Choudhary
H.E.J. Research Institute of Chemistry
International Center for Chemical and Biological Sciences
University of Karachi
Karachi
Pakistan




Contributor(s):
Anabela Pinto Rolo
CNC – Center for Neuroscience and Cell Biology
University of Coimbra
Portugal
/
Department of Life Sciences
University of Coimbra
Portugal


Anu Augustine
Department of Biotechnology and Microbiology
Kannur University
Thalassery Campus
India


Arun Subash Koorapally
Department of Biotechnology and Microbiology
Kannur University
Thalassery Campus
India


Baddireddi Subhadra Lakshmi
Centre for Food Technology
Anna University
Chennai
India
/
Department of Biotechnology
Anna University
Chennai
India


Carlos Marques Palmeira
CNC – Center for Neuroscience and Cell Biology
University of Coimbra
Portugal
/
Department of Life Sciences
University of Coimbra
Portugal


Gopal Thiyagarajan
Department of Biotechnology
Anna University
Chennai
India


Hiu Yee Kwan
School of Chinese Medicine
Hong Kong Baptist University
Hong Kong
China


Ilgın Turkcuoglu
Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility 44280, Faculty of Medicine
University of Inonu
Malatya
Turkey


Jennifer Man Fan Wan
Food and Nutrition Division, School of Biological Sciences
The University of Hong Kong
Hong Kong
China


João Alves Amorim
CNC – Center for Neuroscience and Cell Biology
University of Coimbra
Portugal


João Soeiro Teodoro
CNC – Center for Neuroscience and Cell Biology
University of Coimbra
Portugal
/
Department of Life Sciences
University of Coimbra
Portugal


Megha Valsaraj
Department of Biotechnology and Microbiology
Kannur University
Thalassery Campus
India


Navaneetha Saseendran
Department of Biotechnology and Microbiology
Kannur University
Thalassery Campus
India


Rauf Melekoglu
Faculty of Medicine, Department of Obstetrics and Gynecology, Division of Perinatology
University of Inonu
Malatya
Turkey


Sunil K. Jain
Guru Ghasidas Vishwavidyalaya
Institute of Pharmaceutical Sciences
Bilaspur, Chhattisgarh
India




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