Concept of Molecular Pharmacognosy and Its Development

1.2 Concept of Molecular Pharmacognosy and Its Development

1.2.1 Generation of Molecular Pharmacognosy

Watson and Crick’s discovery of DNA structure in 1953, marking a new era for life science, changed life medicine and thinking ways of scholars in its relevant fields a lot, and since then people began to re-understand life’s nature and laws from the level of biological macromolecules. Although DNA’s discovery and determination bear no stamp on the development of pharmacognosy, they still had an immeasurable impact on the whole life science. Molecular biology developed rapidly and penetrated into the application fi elds of biomedicine, which brought into existence a large number of interdisciplinary sciences, frontier disciplines. Genetic engineering technology based on molecular cloning and reorganization rose, and the related tissue culture technology, especially molecular marker technology based on PCR, sprung up like mushrooms, all of which contributed to fast development of pharmacognosy and a full extension and enrichment of pharmacognosy research areas and methods. Confliction and mutual integration between pharmacognosy and molecular biology brought into forth a new interdisciplinary called molecular pharmacognosy.

Molecular pharmacognosy had the following three theoretical bases. First, the development of molecular biology brought all branches related to biology into a molecular level. Pharmacognosy, with a major concern of plant and animal crude drugs, touched upon many biological theories and methods, so there is no exception to pharmacognosy. Secondly, crude drugs originated in animals and plants, whose cells contained DNA, the material basis to store, duplicate, and transmit genetic information. DNA was also the material base of molecular biology, so pharmacognosy had the combined material base – DNA with molecular biology. This made molecular biology theoretically and methodologically applied to pharmacognosy.

Thirdly, the study level of crude drugs of animals and plants in pharmacognosy developed from organism, tissue, organ, and cell into genetics. Therefore, the advancement of modernization of pharmacognosy had surely a close relation to molecular biology, thus inevitably promoting the study of pharmacognosy into a molecular level.

1.2.2 Concept of Molecular Pharmacognosy

Molecular pharmacognosy is a science dealing with study of classi fication, identification, cultivation, and protection of crude drugs and production of effective element at molecular level. Based on theories and methods of pharmacognosy and molecular biology, molecular pharmacognosy is a promising and prospective branch in pharmacognosy. It can be said that molecular pharmacognosy carries on traditional contents and mission of pharmacognosy and endows pharmacognosy with new tasks and challenges as well.

Discussed from sources of medicines, crude drugs include herbal, animal, and mineral drugs in the broad sense, while in the narrow sense mainly herbal and animal drugs. The study objects of molecular pharmacognosy are limited to the narrow sense. According to different organism levels and gradual combination relation, it can be divided into six major biological levels: gene, cell, organ, organism, population, and community. This biological mode based on multiple levels is called biological spectrum. Each unique level in the biological spectrum is discovered with a historical process. Generally speaking, developing the level of organism in micro- and macrodirection brings into gradual discovery of all levels, as it did in the case of the discovery of cells and genes. Study of the unique scientific questions at each level gives rise to independent branching in life science. The branches such as molecular biology and cytobiology could be mutually promotive but never could be substitutes for each other. These days, pharmacognosy shows a major concern for tissue, organ, organism, and population, upon which relatively mature and independent theory and methods, such as pharmacognosy, histology, and morphology, are brought forth. Molecular pharmacognosy deals with crude drugs at genetic level with a theoretical and methodological basis on gene-level branches – molecular biology.

1.2.3 Major Concern and Main Task for Molecular Pharmacognosy

With a theoretical basis on pharmacognosy, molecular pharmacognosy presents problems to the field of study in pharmacognosy whose major contents can be summarized by authenticity and excellence as presented as follows: (a) Discerning the false from the genuine so as to settle the problem of variety confusion. Due to rise in scope of use and dosage of medicine, plants, animals, and parts with similar appearance or homonym are taken as the same drugs to be used in different regions, thus leading to a lot of confusion; therefore, it is necessary to discern the false from the genuine in terms of their origins, distribution areas. Only in this way can quality be guaranteed. (b) Quality assessment. A systematic study is conducted on crude drugs with multi-origin and genuine quality, including place of origin, harvesting, processing, storage, and the influence of transportation upon active ingredients to confirm high-quality variety and factors that may have effect on it. More than that, excellent varieties should be researched and cultured to achieve fast growth, high quality, and high yield in order to meet the needs of medication.

Scientific connotation of all specific information of authenticity and excellence mentioned above is related to difference in their DNA (except mineral medicines). The fake and the genuine may have different DNA composition due to difference in their origin of varieties; thus, DNA, the genetic material, differentiates the genuine from the fake. Therefore, the scientific connotation of studying molecular pharmacognosy is to research DNA and its relation of its expression of difference to authenticity and excellence of crude drugs.

Molecular pharmacognosy has been given the following main tasks:

1.2.3.1 Systematic Assortment of Varieties of Chinese Herbs and Study of Quality Standardization

Assortment of varieties of Chinese herbs, based on classical taxonomy, can be applied to systematic assortment, classification, and identification, but too many human factors are involved, especially for planted groups of Chinese herbal medicines, such as identification of authentic raw materials, which still remains a problem. Development of species biology and molecular systematics provides an effective weapon and basis for the study of system and evolution, classi fi cation andidentification. Modern species concept has been widely accepted by taxonomists, and pharmacognosists can never ignore theory and fruits in species biology and molecular systematics. Penetration of molecular systematics and application of biological engineering technology provide crude drugs’ classification and identification with an effective weapon and basis to test molecules. To establish a method and system to identify crude drugs based on species biology, molecular systematics, Chinese medicinal resources, and herbalism and to further the development of systematic assortment and standardization of quality of Chinese herbal medicines at the population, individual even genetic level, fall into one of the major concerns of molecular pharmacognosy.

1.2.3.2 Conservation of Medicinal Plant and Animal Biodiversity and Research of Sustainable Utilization of Crude Drugs Resources

DNA diversity is the essence of biodiversity. Molecular makers based on DNA polymorphism analysis and molecular systematics based on genome sequence analysis can directly test DNA variation patterns and determine the key units to protect, so the study of molecular systematics of medicinal plants and animals may presume developing status and endangered degree of the population, thus rendering new operative methods for measurement of biodiversity and countermeasures taken to protect rare medicinal plant and animal resources. Moreover, the application of research findings in molecular systematics based on DNA polymorphism makes the work of hunting for and enlarging the scope of medicinal plant and animal resources more effective and efficient. Expounding the relevance among genetic relationship of DNA molecules, active ingredients, and efficacy in combination of chemical taxonomy, obtaining molecular genetic background of important chemical elements so as to identify whether unknown plants have the genes to produce speci fi c chemical composition, are shortcuts to hunt for and enlarge the scope of crude drug materials by use of molecular systematics.

1.2.3.3 Medicinal Plant Marker Breeding and New Variety Cultivation

In the process of exploring molecular theory and practice, it can be said that molecular detection of genetic diversity and molecular systematics lays a basis for understanding and transforming nature. Exploring and harnessing molecular markers with important traits is the purpose for us to understand and transform nature. With support of cell engineering and genetic engineering, molecular pharmacognosy research becomes more practical. QTL method, which combines breeding technology to the key medicinal plant and animal genetic linkage map constructed by the use of molecular genetic markers, makes it possible to provide information about the mapping of the quantitative traitloci, such as the quantity of genes with target trait, the genetic effects, ways of interaction between genes, and the decomposition of the quantitative traits, which can never be provided by traditional quantitative genetics.

1.2.3.4 Gene Regulation of Metabolic Pathway and Directional Control of the Quality of Chinese Herbal Medicines

More and more attention should be paid to the basic research of secondary metabolite biosynthesis, especially that the research of the gene regulation of key enzymes will be particularly noticeable and then become one of the most challenging and promising direction in molecular pharmacognosy study, for the major source of active ingredients in Chinese herbs is secondary metabolites. The presence or absence of secondary metabolites and their amount decide the quality of Chinese herbal medicine, so carrying out the genetic engineering and improving the content of active ingredients of Chinese herbal medicines will help ease the pressure on the resources of Chinese herbal medicines.

1.2.3.5 The Use of Genetic Engineering and Tissue Culture Technique to Achieve High-Level Expression and Production of Natural Active Ingredients or Genetically Modi fi ed Ingredients

The use of genetically modified organisms as a bioreactor to produce exogenous gene-encoding goods is among the most attractive in genetic engineering, and thus it is called “new-generation pharmaceutical factories.” It has many advantages: it can express complex natural protein in a natural state, it can be obtained continually from animal milk and blood and extracted from bodies of plants, and it can also pass through the digestive tract. In addition, for plant or animal protein with strong active ingredients but side effects as well, such as scorpion venom and trichosanthin, the sequence that decides on toxicity can be removed or inhibited in expression, thus strengthening the expression of the active parts.

Hairy root cultures and crown gall culture – new technologies in combination of plant genetic engineering and cell engineering in recent years – open up a new road for the research and development of production of active pharmaceutical ingredients. With the improvement in expression efficiency and the expanding of the scope of receptor plants, biotechnology will certainly bring a new impetus to the research of adding new genetic characteristics into traditional crude drugs; meanwhile, with the development of new bioreactor technology and the establishment and improvement of efficient cellculture, the commercialization and industrialization of the biotechnology of the natural medicines will speed up.

1.2.3.6 Genetic Engineering and Green Pollution-Free Medicinal Plant

The problem of pesticide pollution in medicinal plants has aroused public concern, for it damages environment, endangers the health, and limits the export of Chinese herbal medicines. Thus, implementing GAP production, advocating green pollution-free medicinal plants, and controlling pesticides without farm chemical in the process of growing medicinal plants become goals for people to achieve. How to improve the ability of medicinal plants against pests via genetic engineering is also one of the tasks for molecular pharmacognosy.