A Journey of Pharmacognosy towards Pharmaceutical Biology
Pharmacognosy was for the first time defined as a pharmaceutical discipline in 1815 by Sydler. Tschirch (1909) gave the following définition (translated from German): " With the name Pharmacognosy we mean the science which has the task to learn everything about drugs originating from plants or animals in all aspects, except the physiological effect, to describe them correctly and under a general vision connect this knowledge".
Originally during the 19th century it was by far the most important pharmaceutical discipline, the "mother" of all present day pharmaceutical disciplines and the beginning of the 20th century—"pharmacognosy" was used to define the branch of medicine or commodity sciences (Warenkunde in German) which deals with drugs in their crude, or unprepared form. Crude drugs are the dried, unprepared material of plant, animal or mineral origin, used for medicine. The study of these materials under the name pharmakognosie was first developed in German-speaking areas of Europe, while other language areas often used the older term “Materia Medica” taken from the works of Galen and Dioscorides. In German the term ‘drogenkunde’ ("science of crude drugs") is also used synonymously. But in 1899, the first signs for a new era became obvious with the introduction of a very successful synthetic drug: Aspirin. The first example of using nature as lead for a new synthetic drug. Despite some obvious failures, such as heroin, gradually synthetic chemistry became more important for developing new drugs. The wish to have pharmaceutical formulations with single pure compounds with well defined activities was an important driving force in this trend. Pharmacognosists have always been very keen in introducing new technologies into their discipline.
As late as the beginning of the 20th century, the subject had developed mainly on the botanical side, being particularly concerned with the description and identification of drugs both in their whole state and in powder form. It was used for the quality control of pharmaceutical preparations from plants. However, for too many years pharmacognosy remained with these methods, and with the rapidly decreasing number of herbal preparations in the pharmacy, the discipline had great difficulties in holding their prominent position in the pharmaceutical curriculum in the sixties and seventies. Fortunately, some visionary Pharmacognosists were able to open up new directions. The development of thin layer chromatography by the well known Pharmacognosist professor Egon Stahl is probably the best example. But also in the field of gas chromatography and high pressure liquid chromatography, Pharmacognosists were among the pioneers in the analysis of plant materials. For studies of the active compounds in plants, these chromatographic methods became important tools. But in that period developing new drugs from plants was not as easy as with synthetic drugs, as the pharmacological test systems, mainly in vivo animal experiments and in-vitro isolated organs, are not suited for bioassay-guided fractionation of active compounds from plant extracts. That requires methods that can readily measure large numbers of samples in a short time. Only for activities for which simple test methods were available, natural products remained a major source for new drugs. This is clearly illustrated by the fact that most of the antibiotics and antitumor drugs are natural products. These activities can be easily tested in in-vitro Systems based on cell cultures. So in the period from 1983 to 1994 of all new approved drugs, 78% of the new antibiotics and 61 % of the new antitumor drugs were natural products or natural products derived.
Then the contemporary study of pharmacognosy was divided into the various fields of
- Medical Ethnobotany: the study of the traditional use of plants for medicinal purposes;
- Ethnopharmacology: the study of the pharmacological qualities of traditional medicinal substances;
- Phytotherapy: the medicinal use of plant extracts.
- Phytochemistry: the study of chemicals derived from plants (including the identification of new drug candidates derived from plant sources).
- Zoopharmacognosy: the process by which animals self-medicate, by selecting and using plants, soils, and insects to treat and prevent disease.
- Marine Pharmacognosy: the study of chemicals derived from marine organisms.
- Analytical Pharmacognosy: Analytical Study of drugs obtained from natural sources.
In 1821, all researchers were believe that combinatorial chemistry and CADD would be better choice for finding new molecule compare to natural source. We have almost wasted 2 decades in finding new molecule through CADD now came back to natural sources. Chemistry is also originated from study of natural sources and coined by the Arabic word ‘kemia’, which was found in Islamic writing. Currently, there is a rapidly increasing interest in Pharmacognosy and natural products research. A number of new international scientific journals in the field illustrate this trend. With the development in the past decade presently we can distinguish three major areas of interest for the pharmacognosist: studies of new biologically active natural products, production of drugs from natural origin, including new methods such as biotechnology and quality control of drugs from natural origin.
Lead finding from nature is an almost infinite source for drug development. The number of organisms that exist in the world is not so easy to assess. The total number of species is estimated to be between 10100 million. The largest diversity is in insects, Plants are in fact a relatively small group with about 250 000 species, of which about 6% has been studied for one or more biological activities, and about 15% has been studied phytochemically. All of these organisms produce a number of secondary metabolites which are connected with the interaction of the organism with its environment. Despite the enormous structural diversity, nature just uses a few building blocks to create this chemodiversity. For exploring nature's chemodiversity, the situation has changed dramatically in recent years by the introduction of high-throughput screening (HTS) methods. By using molecular targets, large number of samples (up to 100000 in 24 hrs) can be screened for a single activity. Obviously, synthetic chemists are not able to produce such numbers of new compounds. Their answer was the development of combinatorial chemistry and testing mixtures of compounds obtained through these novel solid-phase chemical synthetic methods. However, the structural diversity from synthetic chemistry will never match nature, a novel active compound like paclitaxel, having 1,1-asymmetric carbons, will never be designed in a synthetic laboratory. In 2009, India (Pune) was scared of swine flu, we cannot forget the break thought, which was obtained from natural source only. Still precursor of Tamiflu i.e. shikimic acid cannot be prepared synthetically, have to be dependent upon the natural source (e.g.Star anise).
Thus HTS offers new possibilities for natural products. It allows rapid screening of large number of extracts, and it is very suitable for bioassay guided fractionation, which in the past was the major bottleneck in studies of active compounds in plant extracts. Powerful chromatographic methods in combination with HTS are now a very efficient way to new leads for drug development. In the coming years, technological developments will further improve the rate in which new active compounds can be isolated and identified from natural sources. By using pre-fractionation methods, the chances of finding novel compounds will be increased and dereplication, the rapid identification of known active compounds or false positives, will take less time.
A very different approach to lead finding is studying traditional medicines. Such studies can serve two goals: validation of the use of traditional medicines, and finding new leads. With the increased awareness of developing countries that their cultural heritage is a great treasure, studies on traditional medicine are getting more attention. The compounds being responsible for the activity in traditional medicines do not necessarily lead to new drugs. In many cases it might be already known compounds, or compounds that do not perform better than already known drugs. HTS is the field of industrial research; traditional medicine is mainly studied by academic institutions, and governmental laboratories.
From this very brief historical picture, and a short review of some aspects of the present day research, it is clear that Pharmacognosy has entered a completely new era. In the professional situation its role for quality control of herbal drugs has increased and it remains a very important task, which may help to avoid mistakes. The trend that some European governments want to ban phytotherapy out of the health care System carries the risk that such disasters will happen again. All phytotherapy should be in the hands of professionals capable of assuring a proper quality control. In terms of drug development and production, there are numerous new possibilities for the pharmacognosist. Lead finding for drug development using biodiversity or traditional medicines is one major area in which one can see a rapidly increasing activity. In terms of the professional situation, quality control is an important aspect of this field, and pharmacognosy can play here an important role.
Thèse new technologies require, of course, also a new type of pharmacist and pharmacognosist. A pharmacognosist should not only have expertise on the botanical aspects of médicinal plants, but also on phytochemistry, advanced seperation methods, proteins, and molecular biology. Particularly the latter two are new to the field. In the field of proteins it will be proteomics which would fit nicely into the expertise of the pharmacognosists. The molecular biology techniques would be important tools in quality control, not only from biotechnological products, but also in characterizing medicinal plants. That’s why Pharmacognosy now a day’s called as “PHARMACEUTICAL BIOLOGY”
We might be discouraged by the reduction in approach of students to enter in Pharmacognosy. In Pune University, many colleges have no admission in M. pharm Pharmacognosy and few colleges are going to close down this course. Our college (M.M. College of Pharmacy, Thergaon, Kalewadi, Pune) still running this course successfully with minimum admission. But I am sure, we have exciting time ahead. If we just overlook the researchers of different streams of pharmacy in India, everyone is working on natural sources, especially on plants. Maximum journals of research consist of paper from on natural sources. Even new journals are coming everyday for natural products. I will not be wrong if I would say 80% of pharmaceutical researches work on natural sources. And we Pharmacognosists are the one who can understand the natural sources far better than others with few exceptions.
There are many options for the pharmacognosist, but making choices are necessary, we cannot do all. The future is in collaboration between experts, multidisciplinary teams solving scientific (e.g. biological) problems together, rather than mono-disciplinary approaches. Making the drugs of the future by biotechnology, or finding new ones through bioprospecting. In this approach the Pharmacognosists have their contribution with their strong points: natural products isolation, separation and identification, from low molecular weight compounds to macromolecules, including the expertise on biosynthesis of such compounds.
No comments:
Post a Comment