Ethnomedicine: A Source of Complementary Therapeutics
The use of medicinal herbs and herbal medicine is an age-old tradition and the recent progress in modern therapeutics has stimulated the use of natural product worldwide for diverse ailments and diseases.
Ethnomedicine: A Source of Complementary Therapeutics 2010 Editor Debprasad Chattopadhyay ICMR Virus Unit, ID & BG Hospital, GB-4 First Floor, 57 Dr Suresh C Banerjee Road Beliaghata, Kolkata Research Signpost, T.C. 37/661 (2), Fort P.O., Trivandrum-695 023 Kerala, India Published by Research Signpost 2010; Rights Reserved Research Signpost T.C. 37/661(2), Fort P.O., Trivandrum-695 023, Kerala, India Editor Debprasad Chattopadhyay Managing Editor S.G. Pandalai Publication Manager A. Gayathri Research Signpost and the Editor assume no responsibility for the opinions and statements advanced by contributors ISBN: 978-81-308-0390-6 Autobiography of the Editor Dr. Debprasad Chattopadhyay did his Ph.D. in Pharmaceutical Microbiology from Jadavpur University, Kolkata in 1989 after his M.Sc. and then moved to London Hospital Medical College, London as a Visiting Fellow. After a brief training at London under Late Professor J.D. Williams and Dr Jette Elisabeth Kristiansen at Satens Serum Institute, Copenhagen he returned to India and joined the Indian Institute of Chemical Biology (CSIR), Kolkata and then in the Regional Medical Research Centre (Indian Council of Medical Research), Port Blair in 1993 as a Research Scientist. In 1997 he moved to ICMR Virus Unit, Kolkata, at which he is presently working as an Assistant Director (Scientist). He made significant contribution in public health research, particularly in antimicrobial drug development. His in depth studies on ethnomedicinal practices of the Onge, Nicobarese, and Shompen tribes of Andaman & Nicobar Island (by establishing personal relationship with them), help in recording the endemic, threatened and rare flowering plants of Bay Islands. Utilizing the tribal Knowledge-base, he has investigated the scientific basis of those medicaments and identified four herbal leads with antimicrobial, anti-inflammatory, antipyretic, antipsychotic and sperm motility-inhibiting activities. His group has purified and characterized a bioflavonoid that can inhibit the in vitro proliferation of Plasmodium falciparum, the agent of deadly malaria, and is highly effective against the chloroquine-resistant P. falciparum strain. His another contribution is the demonstration of antibacterial activity of methdilazine, a phenothiazine, that produce synergism with aminoglycoside antibiotics. This combination is useful in controlling bacterial resistance as methdilazine alters membrane permeability of bacteria thereby facilitate the entry of antibiotics within the bacterial cell. He has contributed more than 50 research papers, 5 chapters and 5 Review in highly prestigious International Journals like Biotechnology Annual Review, Mini Review in Medicinal Chemistry; New Biotechnology etc., and Books like Modern Phytomedicine: Turning Medicinal Plants into Drugs; New Strategies Combating Bacterial Infection (Wiley-VCH, Germany), Evaluation of Herbal Medicinal Products: Perspectives of Quality, Safety and Efficacy (Royal Pharmaceutical Press, Great Britain) etc. and is the editor of the reference book Ethnomedicine, A Source of Complementary Therapeutics (Research Signpost, India) and Phytotherapy in Diabetes and Hypertension (Bentham Science, USA). He is associated with 18 International peer reviewed Journals as Reviewer and Editorial Board Member of three Journals, published by Bentham Science, Elsevier Science, Global Science Book Publications, Academic Press etc. As Guest Faculty, Examiner, paper setter, Ph.D. guide he is attached with Universities like Jadavpur University, Kolkata; Aligarh Muslim University, Aligarh, Dr MGR University, Chennai etc. He has received awards from the Indian Association of Medical Microbiologists (1988), CSIR Research Associateship (1989-1992), Dr R.V. Rajam Medal from the Indian Association for the Study of Sexually transmitted Diseases & AIDS (1998), International Society of Chemotherapy (1991), Overseas Award from the World Conference on Dosing of Antiinfectives, Germany (2004), Professor Amiya Bose Oration Award from Indian Dietetic Association (2008 and 2009), Indian Science Communicator Award in 2nd Rastriya Vigyan Sancharak Sammelan 2009 by the Department of Science & Technology, Government of India. Dr Chattopadhyay also chaired the scientific session in the International Conference on Drug Delivery and Drug Targeting Research, Kolkata in 2008, and International conference on Herbal Medicine Evaluation of Quality, Efficacy and Safety, Bangalore in 2009. He is the member of different Selection Committee for Government funded research projects, and for the selection of teaching faculty of University and Colleges. He has four patents in his credit and handled several projects of national importance, including ethnomedicinal projects with grass root innovators. Foreword The use of medicinal herbs and herbal medicine is an age-old tradition and the recent progress in modern therapeutics has stimulated the use of natural product worldwide for diverse ailments and diseases. The educated public and health professionals have enormous interests in the medicinal uses of herbs but, unfortunately, there is a great deal of confusion about their identification, effectivity, therapeutic dosage, toxicity, standardization and regulation. According to WHO, ethnomedicine is popular in all regions of the developing world and its use is rapidly expanding in the developed countries, for example, in China traditional herbal preparation account for 30-50% of the total medicinal consumption. In Ghana, Mali, Nigeria and Zambia, the first line treatment for 60% of children with malaria is the use of herbal medicine. In San Francisco, London and South Africa, 70% of people living with HIV/AIDS use traditional medicine. Today the annual global market for herbal medicine stands at over US $60 billion. Western trained physicians should not ignore the impact of ethnomedicine on their patients. Human evolution across time represents a fascinating story in the parlance of biology. However, the journey was not trouble free. In our sustenance and perpetuation many odds like disease posed serious threat towards very survival of mankind. Many a time's history has witnessed epidemics leading to the loss of huge lives across continents imposing high economic, social and psychological costs. Therefore, it was important to prevent diseases, maintain and restore the health of those who fall ill. Every human community responded to this challenge by developing a system for health care. Hence, the medicinal system reflects the interaction and synergy of social and cultural system. Since prehistoric times, human beings have found remedies within their habitat and have adopted different therapeutic strategies depending upon climatic, phytogeographic, floral and faunal characteristics as well as their cultural and socio-structural typologies. Traditional systems thus, contain beliefs and practices in order to avoid, prevent or avert ailments, which constitute traditional preventive medicine. The medicinal systems based on cultural framework thus created a new discipline of "ethnomedicine". (eth�no�med�i�cine/eth no-med�-sin/ Ethnomedicine eth �n�me �di�sin) or ethnic medicine or "folk medicine" is the medical systems based on the cultural beliefs and practices of specific ethnic groups or particular culture and concern about the care and treatment of illness. The study of etiology of disease, practitioners and their role in health care, and types of treatment administered are the purview of ethnomedicine, which helps in the search for new cures and wellness among indigenous people. At large, ethnomedicine is a sub-field of ethnobotany or medical anthropology of all cultures either written (e.g. Traditional Chinese Medicine, Ayurveda), or orally transmitted over the centuries. In the scientific arena, it deals with the use of several health promoting practices and natural products for the maintenance of optimal physical and emotional health, as well as prevention and treatment of diseases. The term "traditional" imply repetition from generation to generation developed on careful observation by traditional healers in a given generation of indigenous people, compare their personal experiences with what they have been told by their teachers and neighbours, conduct experiments to test the reliability of their knowledge, aa well as to enhance and improvise their findings. The "tradition" about traditional knowledge is not its antiquity but the way of acquiring and use, which is unique to each indigenous culture. In almost all ethnomedicinal system the cause of diseases are commonly described as "natural" and "magical" or "supernatural", and illness caused by angry deities, ghosts, ancestors and witches fall into the first category; while those due to an upset in body humors and consequently lose of bodily equilibrium fall into second. This stands in contrast to that of natural causes, where illness is explained in impersonal, systemic terms. The intrusion of heat or cold into or their loss from the body upsets the basic equilibrium; the balance of humors off the dosha of Ayurveda, and the Yin and Yang of Chinese medicine must be restored if the patient is to recover. The natural environment is a living incubator where the components like land, sea, atmosphere, the flora and the fauna are linked and interact with human being in an intrinsic manner. Therefore, plants play a participatory role in healing. A healer's power is determined by the magnitude of his understanding of the natural laws for the benefit of patients and the whole community. Ethnomedicine in many cultures is used as healing traditions over centuries, embraces on the belief that the earth plays a vital role in one's spiritual, emotional, and physical well-being, and these methods are effective in many cases as biomedical treatment. The western medicine is much more technical and analytical, while traditional practices are much more holistic. Good health, disease, success or misfortune are not seen as random but arise as a result of the individuals' actions and the balance or imbalance between the individual and the social environment. Use of herbal remedies in Africa, South America and Asia, some parts of Europe represents a long history of human interactions with the environment. Plants used in traditional medicine contain a wide range of metabolites that can be used to treat chronic as well as infectious diseases. A vast knowledge about the use of plants against different illnesses may be expected to have accumulated in areas where the use of plants is still of great importance. The medicinal value of plants lies in either alone or in combination of some phytochemicals that produce a definite physiological action on the human body. The most important of these bioactive compounds are alkaloids, flavanoids, tannins and phenolics. Medicinal plants or its components used in traditional medicines are usually less or non-toxic due to time tested selection, and traditional dosage in liquid form to encourage the use of extremely low concentration of the active ingredients. However, the problem of toxicity arises due to human manipulation to increase the accumulation of the active compound for increased bioactivity. Therapeutically active molecules in plants exists in a mixture with other phytochemicals like tannins, carbohydrates, amino acids, proteins, vitamins, trace metals, etc. Moreover, the human body is well acquainted to these natural extracts, most of which, in other forms, are consumed as food. Thus, usually these herbs do not upset or inflict toxicity in the body, but help in maintaining the physiological homeostasis by and large. Single isolated compound as drugs possess all other substances with which they co-exist in the plant in natura. It has been suggested that the reactivity of a single pure compound as drug with the body's physiological medium leads to the manifestation of drug toxicity. Phytomedicines with a little amount of processing can promote the healthy development of the body (health food) since it contains not only the active drug molecule, but also other substances required to maintain the overall physiological functions of the body synergistically. This is why `bitter leaf' Vernonia amygdalina can be used as a food and as a drug for diabetes without apparent toxicity. However, the purified extracts or concentrated isolates are considered as medicines and must be subjected to rigorous standardization used to test medicinal agents. Phytochemical studies must be tailored to match the biological activity while the chemical studies should provide information that help in standardization and quality control of the finished product. Research interest and activities on ethnomedicine have increased tremendously in recent time and scientific research has made important contribution to the understanding of traditional subsistence, medical knowledge, wisdom and practice. The explosion of ethnomedicinal literature help in increased awareness among people, the recognition of indigenous health concepts as a means of ethnic identities, the search for new treatments and technologies. The ethnomedicine have long been ignored by biomedical practitioners as the chemical composition, dosages and toxicity of ethnomedical plants are not clearly defined. However, ethnomedicinal uses of plants are one of the most successful criteria in finding new therapeutic agents. Some outstanding drugs developed from the ethnomedicinal uses include: vinblastine and vincristine from Catharanthus roseus for treating lymphoma and leukaemias, reserpine from Rauwolfia serpentina for hypertension, aspirin from Salix purpurea for inflammation, pain and thrombosis and quinine from Cinchona pubescens for treating malaria. This reference book is an attempt to summarize the current knowledge of promising ethnomedicines and their phytophores, to compounds tested against diverse diseases. The therapeutic properties and structure activity relationship (SAR) of some important and potentially useful ethnomedicines is addressed with a focus on how these ethnic knowledge can led to the development of useful therapeutic lead for preclinical or clinical evaluation. In general it is a snapshot of different areas of research on the role of phytochemicals in health, comprehensively presented and is useful of tidbits of knowledge or ideas for research, covering the ethnomedicines uses in the management of several diseases, particularly, infectious diseases (like viral, bacterial and fungal) and lifestyle related disorders mostly validated by modern scientific methods. In depth information prepared by experts all over the globe traces the evolution of herbal drugs with civilization and their use as antiviral, antibacterial, antifungal, antiparasitic, antioxidants, anticancerous, chemopreventors, memory enhancers, neuroprotective, immunomodulator, laxatives, analgesic and anti-inflammatory disorders, along with safety issues and toxic effects. The special emphasis covers twelve important topics like Diseases that need new drugs, role of ethnomedicine as complementary therapeutics, ethnomedicnal plants in parasitic infections, ethnomedicines for the development of anti-herpesvirus agents, ethnomedicinal plants derived antibacterials, recent advances in antimicrobial effects of essential oils, ethnomedicnal plants to fight neoplastic diseases, recent advances on ethnomedicinal immunomodulatory agents, plant based treatment of Alzheimer's disease, ethnomedicinal plants as antiinflammatory and analgesic agents, ethnomedicnal plants as laxative drugs and the relationship of ethnomedicines with pharmacogenomics. This book offers researchers working on diverse aspects of medicinal plants with a complete coverage of botany, ethnology, pharmacology, toxicology and medicinal properties, and provides essential source material to all working in the fields of botany, pharmacy, traditional systems of medicine and drug industry. This book is the outcome of extensive consultations among biomedical scientists and clinicians and I am immensely grateful to those colleagues for their support in developing the concept. My thanks go to Dr. Shankar Pandalai, Managing Editor and A. Gayathri, Publication Manager of the Research Signpost for their suggestions and help in producing this book. With great pleasure and respect, I extend my sincere thanks and indebtedness to all the contributors, particularly Professor Joseph Molnar, Dr Iqbal Ahmad, Professor George Varughese, Dr. Mahmud Tareq Hassan Khan, Dr. Biswajit Mukherjee, Dr. Pulok Mukherjee, Professor C.K.K. Nair, Professor Ilkay Orhan, Professor Wandee Gritsanapan, Dr. Mahiuddin Alamgir and Dr. M. Anilkumar, for their response, excellent updated contributions and consistent cooperation as well as patience. I express my deep gratitude to all those scientific colleagues and teachers, who not only contributed their work but also, help me in reviewing the manuscripts time to time. I am indebted to the Officer in-Charge of the ICMR Virus Unit, Kolkata and the Research Signpost, Thiruvanandapuram, India for their support and interest to made this volume possible. Dr. D. Chattopadhyay Contents Chapter 1 Diseases that need new drugs: Need of the hour Debprasad Chattopadhyay, Paromita Bag and Sujit K Bhattacharya Chapter 2 Ethno medicine in complementary therapeutics Pulok K. Mukherjee, S. Ponnusankar and M. Venkatesh Chapter 3 Ethnomedicinal plants in parasitic infections Varughese George, Sabulal Baby and Anil John J Chapter 4 Ethnomedicines for the development of anti-herpesvirus agents Debprasad Chattopadhyay, Sonali Das, Sekhar Chakraborty and Sujit K Bhattacharya Chapter 5 Ethnomedicinal plants derived antibacterials and their prospects Maryam Zahin, F. Aqil, M. S. A. Khan and Iqbal Ahmad Chapter 6 Recent advances in research of antimicrobial effects of essential oils and plant derived compounds on bacteria Zsuzsanna Schelz, Judit Hohmann and Joseph Molnar Chapter 7 Ethnomedicinal plants to fight neoplastic diseases C. K. K. Nair, P. Divyasree and G. Gopakumar 1 29 53 117 149 179 203 Chapter 8 Recent advances on the ethnomedicinal plants as immunomodulatory agents Mahiuddin Alamgir and Shaikh Jamal Uddin Chapter 9 An update on plant-originated treatment for Alzheimer's disease Ilkay Orhan, G�rdal Orhan and Bilge ener Chapter 10 Ethnomedicinal plants as anti-inflammatory and analgesic agents M. Anilkumar Chapter 11 Ethnomedicinal plants popularly used in Thailand as laxative drugs Wandee Gritsanapan Chapter 12 Ethnomedicines and pharmacogenomics Biswajit Mukherjee, Biswadip Sinha and Soma Ghosh 227 245 267 295 317 Research Signpost 37/661 (2), Fort P.O. Trivandrum-695 023 Kerala, India Ethnomedicine: A Source of Complementary Therapeutics, 2010: 1-28 ISBN: 978-81-308-0390-6 Editor: Debprasad Chattopadhyay 1. Diseases that need new drugs: Need of the hour 1 Debprasad Chattopadhyay1, Paromita Bag1 and Sujit K Bhattacharya2 ICMR Virus Unit, ID & BG Hospital, GB-4, First Floor, 57 Dr Suresh C Banerjee Road, Beliaghata Kolkata; 2Additional Director General, Indian Council of Medical Research, Ansari Nagar New Delhi 110029, India Abstract. Studies on new drugs for malaria, trypanosomiasis, filariasis, tuberculosis, schistosomiasis, leshmaniasis and amoebiasis came almost to a standstill; while there is no suitable drug to stop the emerging, re-emerging and the drug-resistant pathogens. On the other hand, the clinical efficacy of many ethnomedicines or compounds of natural origin was not yet evaluated and the composition of many traditional preparations was only crudely analysed. Pharmaceutical scientists are experiencing difficulty in identifying new lead structures in the finite world of chemical diversity as most synthetic drugs have unacceptable side effects. While many ethnomedicinal molecules like artemisinin, baccosides, curcumine, picrosides, piperidines, phyllanthins, psoralens, quinghaosu, rauwolfia alkaloids, steroidal lactones and glycosides, ursolic acid, withanolides showed impressive successes. The need of the hour is to develop new effective drugs against protozoal (malaria, trypanosomiasis, filariasis, schistosomiasis, leshmaniasis and amoebiasis), emerging and re-emerging viral and bacterial diseases, drug resistant microbes, chronic and difficult-to-treat diseases (like cancers, cardiovascular disease, diabetes, rheumatism etc), and prion diseases. This review will highlight the pros and corn of those diseases that need the new drugs and the recent research on the line. Correspondence/Reprint request: Dr. Debprasad Chattopadhyay, ICMR Virus Unit, ID & BG Hospital, GB-4 First Floor, 57 Dr Suresh C Banerjee Road, Beliaghata, Kolkata. E-mail: firstname.lastname@example.org 2 Debprasad Chattopadhyay et al. Introduction Disease and drug A disease is a pathological condition or abnormality of body (cell, organ, or system) and or mind of an organism resulting from infection, genetic defect, or environmental stress, and characterized by an identifiable group of signs or symptoms that causes discomfort, dysfunction, distress, or death to the person afflicted or those in contact. Literally, a disease refers to the invasion of the body by pathogens, hence, Pathology is the study of diseases, while the systematic classification of diseases is referred to as Nosology; but the knowledge about diseases and their treatments is Medicine. Medical science distinguishes a disease, having a known specific cause(s), called its etiology, and a syndrome is a collection of signs or symptoms that occur together. Many different intrinsic (genetic defects or nutritional deficiencies) or extrinsic (environmental exposure, such as second-hand smoke) factors alone or together can cause disease, while for many a cause cannot be identified. These factors are broadly categorized into: social, psychological, chemical and biological. Biological causes is considered as a spectrum where a disease is either caused by genetic factors (e.g. CAG repeats in Huntingtin gene causes Huntington's Disease) or environmental factors (like toxic acetaldehyde in cigarette smoke and dioxins from Orange) and infectious agents (e.g. smallpox virus, poliovirus, bacteria). In between, genes (e.g. NOD2/CARD15) and environmental factors (Gut microbiota) interact to cause disease (inflammatory bowel disease, Crohn's Disease). Koch's postulates is used to determine whether a disease is caused by an infectious agent, while family inheritance pattern determine the genetic factors (e.g., inheritance of hemophilia in the British Royal Family). Now Apoliprotein E (ApoE) gene is found to be a susceptibility gene for Alzheimer's disease (Bekris et al., 2008). Similarly segregation of genes or genetic markers like single nucleotide polymorphism (SNP) or expressed sequence tag throughout the genome contributes many diseases (McVean et al., 2005; Skelding et al., 2007). Hence, disease can be broadly classified on the basis of its cause as: genetic diseases, infectious diseases, and non-infectious (including lifestyle related) diseases. An infectious diseases is the result of attack by a acellular (prion, virus) or cellular organism (bacteria, fungus, parasites etc.), a genetic diseases is due to defect in genetic makeup or genetic change, while the lifestyle related disorders are due to change in several physiological and environmental factors. The word "drug" is etymologically derived from the Dutch/low German word "droog" (means dry), since historically most drugs were dried plant Diseases that need new drugs: Need of the hour 3 parts. A drug is any substance that can modify a chemical process or processes in the body, like to treat an illness, relieve a symptom, enhance a performance or ability, or to alter states of mind. Drug can be a biological substance (natural), synthetic or semi-synthetic, that is taken for non-dietary needs, usually synthesized as secondary metabolites of living organisms (bacteria, fungi, higher plants and animals), or outside of an organism, but introduced into an organism to produce its action. That is, when taken into the body, it will produce some effects or alter some bodily functions (relieving symptoms, curing diseases or as preventive medicine etc). The endogenous biochemicals (such as hormones) can bind to the same receptor in the cell, producing the same effect as a drug. Thus, drug is merely an artificial definition that distinguishes whether that molecule is synthesized within or outside an organism. For instance, insulin is a hormone that is synthesized by the pancreas inside the body, but if it is introduced into the body from outside, it is considered as a drug. Problems and prospect The Pharmaceutical research got momentum when natural product chemists and pharmacologists, began to unravel the chemistry of traditional medicines. Scientific advancement led to the identification of many molecules as novel compounds and many new drugs against infections, cancers, ulcers, heart diseases were emerged; while many developed through random screening of plants; and many others resulted from sharp-eyed observations of scientists (Patwardhan et al., 2004). Studies on new drugs for malaria, trypanosomiasis, filariasis, tuberculosis, schistosomiasis, leshmaniasis and amoebiasis came almost to a standstill; while there is no suitable drug to stop the emerging and re-emerging microbes, particularly the drug-resistant pathogens. On the other hand, the clinical efficacy of many ethnomedicines was not yet evaluated and the composition of many traditional preparations was only crudely analysed. Pharmaceutical scientists are experiencing difficulty in identifying new lead structures in the finite world of chemical diversity as most synthetic drugs have unacceptable side effects. On the other hand, ethnomedicinal molecules like quinghaosu, artemisinin, rauwolfia alkaloids, psoralens, holarrhena alkaloids, guggulsterons, mucuna pruriens, piperidines, baccosides, picrosides, phyllanthins, curcumine, withanolides, steroidal lactones and glycosides showed impressive successes. A whole range of chronic and difficult-to-treat diseases such as cancers, cardiovascular disease, diabetes, rheumatism, AIDS, neglected tropical diseases and diseases caused by drug resistant microbes require new effective drugs. 4 Debprasad Chattopadhyay et al. A major problem with traditional, indigenous medicine is its reliability and standardization, whereas most of the modern medicine have unacceptable side effect, high cost, and unsuitable for all conditions. In the bioprospecting of new medicine, the use of indigenous medicine is broken down, as the indigenous population has been marginalized or limited to small groups or small geographical areas, as in Africa. The Ayurveda and Chinese traditional medicine (CTM) are `great traditions', while the traditions of Africa, Tibet, Chakma (Chakma Tilaka Chikitsa of Chakma tribes, Bangladesh) are excellent repository of knowledge. However, researchers usually exploited poisonous sources because it is relatively easy to demonstrate; spread easily by word of mouth; and can differentiate between ordinary and extraordinary materials. But a considerable time is required to demonstrate true medicinal activities of a plant with a proven safety profile. As the Ayurveda and CTM have relatively organized database and easy to test by modern methods, hence have an important role in the bioprospecting of new medicines. Table 1 shows the major communicable and non communicable diseases that need new drugs. Table 1. The diseases that can cause major devastation worldwide and need new drugs. Infectious diseases and its global burden For centuries infectious diseases pose major challenges to human progress and survival, and remain the leading causes of death and disability worldwide. Periodic emergence of new and old infection epidemics greatly magnifies the Diseases that need new drugs: Need of the hour 5 global burden of infections. Studies of these emerging infections reveal the evolutionary properties of pathogens and the dynamic relationships between microbes, their hosts and environment (Morens et al., 2004). The infections that have newly appeared in a population or existed previously and now rapidly increasing in incidence or geographic range is called emerging infection (EI). Acquired immune deficiency syndrome (AIDS) caused by human immune deficiency virus (HIV) was first recognized in 1981, and as a global killer HIV/AIDS now threatens to surpass the Black Death of the 14th century and the 1918-1920 influenza pandemic, each of which killed nearly 50 million people. Of the 'newly emerging' and 're-emerging/resurging' diseases after HIV/AIDS, the monkeypox, severe acute respiratory syndrome (SARS) in 2003, bird flu in 2006 and swine flu in 2009 had a worldwide impact; while the 2001 anthrax bioterrorist attack in US was a 'deliberately emerging' diseases. Actually emergence results from dynamic interactions between rapidly evolving infectious agents and changes in environment and host behaviour that provide such agents a favourable ecological niche (Morens et al., 2004). It was estimated that infectious disease alone contribute about 15 million (>25% of 57 million) annual deaths worldwide, and an additional millions of deaths from past infections (like streptococcal rheumatic heart disease) and complications with chronic infections, such as liver failure and hepatocellular carcinoma in people with hepatitis B or C (WHO Report 2004). The burden of morbidity (ill health) and mortality in infectious diseases is more in developing countries (Guerrant & Blackwood, 1999), particularly on infants and children (about 3 million children die each year from malaria and diarrhoeal diseases); while in developed nations mortality in infectious disease disproportionately affects indigenous and disadvantaged minorities (Butler et al., 2001). Old microbes cause new diseases and the newly emerging infections Some infections once caused familiar diseases, but now causing new or uncommon diseases as found with Streptococcus pyogenes (caused a fatal pandemic of scarlet and puerperal fevers between 1830 and 1900) is now rare (Katz & Morens, 1992), and replaced by streptococcal toxic shock syndrome, necrotizing fasciitis and re-emergent rheumatic fever (Musser & Krause, 1998). Sometimes the diseases causing ability of a new microbe are delayed, as found with Koch-Weeks bacillus discovered by Robert Koch in 1883. More than a century later, a virulent clonal variant of Koch-Weeks bacillus or Haemophilus influenzae biogroup aegyptius was found to be responsible for Brazilian purpuric fever, a fatal emerging infection (Musser & Selander, 1990). Although the basis of emergences and severity of S. pyogenes and H. influenzae biogroup aegyptius are not fully known, but complex microbial genetic events are suspected. PCR 6 Debprasad Chattopadhyay et al. studies demonstrate that a unique plasmid, and chromosomal regions of H. influenzae biogroup aegyptius are responsible (Li et al., 2003). Similarly the virulence in S. pyogenes is due to factors like M1 surface protein, M proteins, bacteriophage-encoded superantigen toxins and a sic (streptococcal inhibitor of complement) protein selected by human mucosal factors (Reid et al., 2001; Beres et al., 2003). Evidence suggest that changes in streptococcal virulence reflect genetic changes associated with phage integration, large-scale chromosomal rearrangements and the shuffling of virulence cassettes (clusters of genes responsible for pathogenicity), followed by rapid human spread and immune selection (Reid et al., 2001; Beres et al., 2003). Newly emerging infectious on the otherhand are those which are not previously recognized in man, but now cause due to genetic mutation (microbes), genetic recombination or reassortment (viruses), changes in populations of reservoir hosts or intermediate insect vectors, microbial switching from animal to human hosts, human behaviour (human movement and urbanization), and environmental changes. The microbial, host and environmental factors interact to create opportunities for infectious agents to evolve into new ecological niches, reach and adapt to new hosts, and spread more easily between them (Chattopadhyay & Naik, 2007). Some chronic diseases have microbial aetiology Infectious agents associated with chronic diseases are one of the most challenging categories, as evident from the associations of hepatitis B and C with chronic liver damage and hepatocellular carcinoma, certain genotypes of human papillomaviruses (HPV) with cervical cancer, Epstein-Barr virus with Burkitt's lymphoma (largely in Africa) and nasopharyngeal carcinoma (in China), human herpesvirus 8 with Kaposi sarcoma, and Helicobacter pylori with gastric ulcers and gastric cancer (Chang et al, 1994; Parsonnet, 1999; Sanders & Peura, 2002). Interestingly cardiovascular disease and diabetes mellitus, a major cause of global death and disability, is now suggesting infectious aetiologies (Fredricks & Relman, 1998). Re-emerging/resurging infections and global spread Re-emerging and resurging infections existed in the past but are now rapidly increasing either in incidence or in geographical or human host range. Re-emergence is caused by microbial evolutionary vigour, zoonotic encounters and environmental encroachment, and re-emergences or cyclical resurgences of some diseases may also be climate-related, for example, the El Ni�o/Southern Oscillation phenomenon is associated with resurgences of cholera and malaria (Kovats et al., 2003). World is now a global village and Diseases that need new drugs: Need of the hour 7 travel has an important role in bringing people into contact with infectious agents (Cliff et al., 2002). An increase in travel-associated diseases, anticipated in 1933 (Massey, 1933), is now demonstrated by an international airline hub-to-hub pandemic spread of acute haemorrhagic conjunctivitis in 1981 (Morens, 1998), epidemics of meningococcal meningitis associated with the Hajj, exportation of epidemic SARS from Guangdong Province of China to Hong Kong to Beijing, Hanoi, Singapore, Toronto and elsewhere (Peiris et al, 2003), Bird flu and swine flu from Europe to Asia in 2006 and 2009. The persistent spread of HIV along air trucking, drug-trafficking and troop-deployment routes is a deadly variation on this theme (Quinn, 1994; Daley et al, 1999; Ronald, 1995). Prion diseases A prion is an abnormal, transmissible agent that induces abnormal folding of normal cellular proteins in the brain, leading to rapidly progressive brain damage and death. Prion diseases or transmissible spongiform encephalopathies (TSEs) are a family of rare progressive neurodegenerative disorders that affect man and animals, with a long incubation periods, spongiform changes with neuronal loss, that failed to induce inflammatory response (Aguzzi & Heikenwalder, 2006). Injections of ground-up brain tissue from an affected animal or man into another animal transmit the disease, suggesting that the disease is caused by a virus like agent. But no genome was identified from such brain tissues, and treatment with UV light (that destroy DNA) does not reduce its infectiousness, indicate that the causative agent is not a virus. To date, the evidence indicates that the infectious agent of TSEs is a protein (Aguzzi & Heikenwalder, 2006), called "prion proteins" (PrP) or simply prions by Stanley Prusiner that bring him the Nobel Prize in 1997 (Prusiner, 2001). The normal cellular protein (PrPC) are transmembrane glycoprotein on the surface of certain cells (neural and hematopoietic stem cells) is easily soluble, digested by proteases and is encoded by a gene PRNP located on chromosome no 20. While the abnormal, diseaseproducing protein PrPSc (for scrapie) has the same amino acid sequence in their primary structure but secondary structure contain beta conformation, insoluble in solvents (except the strongest solvents) and resistant to proteases. When PrPSc comes in contact with PrPC, it converts the three-dimensional configuration of PrPC into more of itself, and bind to each other forming aggregates (Mead, 2006). It is not clear whether these aggregates directly cause the cell damage or are cellular dame is a side effect of the disease process. Prion diseases are either inherited or infectious. Inherited Prion Diseases are spontaneous and inherited with infectious maladies. It includes (i) Creutzfeldt-Jakob disease (CJD): 10�15% are inherited (the patient comes from a family in which the disease has appeared 8 Debprasad Chattopadhyay et al. before) as an autosomal dominant mutated PRNP gene. (ii) GerstmannStr�ussler-Scheinker disease (GSS) caused by the inheritance of a PRNP gene with a mutations encoding leucine instead of proline at position 102 (P102L) or valine instead of alanine at position 117 (A117V). (iii) Fatal Familial Insomnia (FFI), a rare disorder inherited by a PRNP gene with asparagine instead of aspartate at position 178 (D178N), the susceptibility polymorphism of methionine at position 129 of the PRNP gene; and extracts from autopsied brains of FFI victims can transmit the disease to transgenic mice (Johnson, 2005). Infectious Prion Diseases includes (i) Kuru, first found among the Fore tribe in Papua New Guinea whose rituals included eating the brain tissue of their recently deceased members. The disease is now disappeared as this practice was halted. (ii) Scrapie of sheep (and goats) transmitted from animal to animal by contaminated feed with nerve tissue, or by injection of brain tissue. (iii) Bovine Spongiform Encephalopathy (BSE) or "Mad Cow Disease", found in Great Britain in 1985, among cattle feed that contained brain tissue from sheep infected with scrapie (Aguzzi, 2006), and was declined as the use of such food was banned after epidemic in 1992. Another similar disease Variant Creutzfeldt-Jakob disease (vCJD) was also noticed in Great Britain cattle herds. Even though the cow and human PRNP genes differ at 30 codons, their prion sequences (all patients are homozygous for the susceptibility polymorphism of methionine at position 129) suggests that these patients (155 by 2005) acquired the disease from eating contaminated beef (Glatzel et al., 2005). The changes in slaughter techniques that mix cattle nervous tissue in beef for human consumption in 1989 now restrict the disease. Prion diseases are fatal, and death occurs within a year after the first symptoms (Will et al., 1999; Carsten Korth et al., 2001). There is no suitable therapy exists till date and devising approaches to the therapy of prion diseases is extremely difficult because of the mysterious nature of the infectious agent, its composition, structure, mode of replication and the mechanism of pathogenesis. As the disease affects the brain parenchyma, so the therapeutic agents need to cross the brain-blood barrier or to be introduced directly into the cerebrospinal fluid or brain tissue, and the disease is noticed only after onset of severe clinical symptoms (Prusiner, 2001). However, many compounds can inhibit prion propagation in rodents (Kimberlin & Walker, 1983; Dickinson et al, 1975; Diringer & Ehlers, 1991; Ehlers & Diringer, 1984) but treatment with these compounds was ineffective, like congo red inhibit PrPSc formation (Caughey & Race, 1992; Caspi et al., 1998; Priola et al., 2000) in rodents but ineffective when neurologic signs appear (Ingrosso et al., 1995). Because the blood-brain barrier restricts the access of many molecules to the CNS, and thus agents or drugs that can cross this barrier have been screened for their ability to inhibit PrPSc formation. The acridine and Diseases that need new drugs: Need of the hour 9 phenothiazine derivatives (a tricyclic scaffold and a side chain moiety) used against psychoses (Delay et al., 1952) showed that chlorpromazine inhibited PrPSc formation (at 3 �M), whereas quinacrine (a structural antecedent of the phenothiazines) was 10 times more potent due to its aliphatic side chain (Korth et al., 2001). Earlier reports also indicated the potent inhibition of PrPSc formation by acridine and chlorpromazine (Roikhel, et al., 1984; Dees et al., 1985). Quinacrine and other lysomotrophic reagents added to ScN2a cells can clear PrPSc (Doh-urs et al., 2000), as quinacrine, can cross the blood brain barrier, and for the treatment of CJD and other prion diseases, with a daily oral tolerable dose of 1001,000 mg (Phuan et al., 2007). To date, several compounds have been tested that decrease PrPres concentration in scrapie-infected cell lines or prolong the incubation period in vivo. These include sulfated polyanions (Farquhar et al., 1999; Huang et al., 2002), amphotericin B derivatives (Adjou et al., 2000), Congo red (Demaimay et al., 1998), tetracyclic compounds (Forloni et al., 2002), tetrapyrroles (Priola et al., 2000), branched polyamines (Supattapone et al., 2001) and -sheet breakers derived from PrP