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High-yielding cell cultures

#KR-2240


Biotechnological production of a valuable secondary metabolites on the basis of high-yielding cell cultures of medicinal plants of Kyrgyzstan

Tech Area / Field

  • BIO-CGM/Cytology, Genetics and Molecular Biology/Biotechnology
  • BIO-CHM/Biochemistry/Biotechnology
  • BIO-DIV/Biodiversity/Biotechnology
  • MED-DRG/Drug Discovery/Medicine

Status
3 Approved without Funding

Registration date
25.01.2016

Leading Institute
National Academy of Sciences of Kyrgyzstan / Biotechnology Institution, Kyrgyzstan, Bishkek

Collaborators

  • Department of Environmental Health Science, Nara Women's University, Japan, Nara\nKobe Gakuin University, Japan, Kobe\nYamanashi University, Japan, Kofu

Project summary

Currently, various researchers elsewhere carry out activities on searching new types of promising plants for the pharmacological industry. Ongoing activities may be decreasing available natural stocks of plant-based raw materials. Hence, the need for using biotechnology applications that leads to environmentally friendly materials for producing herbal-based medicines [1]. According to FAO [2] more than 50,000 species of plants are used in official and folk medicine. There has been an increasing demand for herbal medicinal products recently. For these purposes it has been widely used cell technology to produce biologically active substances. There are, however, some difficulties to succeed in this endeavor, e.g. the lack of initial plant species to develop lines and cell lines.
Many pharmacologically promising plants contained main active ingredients in the roots. Uncontrolled, and often illegal, collecting of roots and rhizomes of medicinal plants leads to the erosion (and even loss) of their natural populations, and sometimes ends with stopping the production of medical drugs. New approaches are required to address this problem. One is the development, through biotechnology methods, of culture cells, tissues and isolated plant organs that could synthesize valuable biologically active compounds. These cultures should be able to synthesize the whole spectrum of secondary metabolites typically in the organs of whole plant and transfer to cultures of undifferentiated cells and tissues. During the process of dedifferentiation they may, however, lose their ability to biosynthesis of secondary metabolites. Intensive growth activity of root crops and their ability to grow on simple (without hormones) media allows getting large numbers of eco-friendly roots with chemical composition close to the native plant species [3-6]. These characteristics can be used as the source for the commercial application of modern biotechnology and other methods for producing medicinal raw materials. There is a great interest for using special bioreactors for cultivation of roots. They need to be standardized for ensuring appropriate and reliable cultivation conditions. Research on the flora of various regions of the Earth, including biopersity hot spots of Kyrgyzstan will allow expanding the range of plants for its use in pharmacology (i.e., plant-base medicine) [7].
Kyrgyzstan is one of the centers of origin of various cultivated plants. The flora of its mountain regions is very perse and shows a high endemism [8-10]. This region could be a target for searching new sources of biologically active substances. Special attention can be given to flavonoids of plant origin, especially those widely use in official and traditional medical practices. Phenolic compounds have a wide range of therapeutic action. In this regard, an important challenge is the search of new promising species for further use in medicine as drug of different action.
We have conducted (including also in frame of ISTC KR-973 project) preliminary phytochemical studies of native plants endemic, rare and economically valuable species of flora of Kyrgyzstan. The accumulation of flavonoids and antioxidant activity in 473 species of plants from 228 genus and 54 families was determined. We found a large group (180) of interesting plant species with more than 2% of flavonoids content. Many of them were endemic (60 species) or sub-endemic (18) species.
From the literature [6, 11-19] and own search we understand that in vitro culture, (including the culture of transformed roots) have a high potential [20-22]. In our joint research with a group of specialized roots of the Institute of Plant Physiology Russian Academy of Sciences, Moscow (NSF project, # IZ73ZO_127969) we got a callus culture and hairy root culture of the endemic species Scutellaria andrahnoides Vved ex Juz., which shows a high content of flavones (baicalein, wogonin and corresponding to them glucuronides - baicalin and vogonozid). These flavones have a wide range of physiological activity and are popular in modern traditional and official medicine [15, 23]. Wogonin has the selective ability to inducing apoptosis only oncogenic cells. Selective cytotoxic activity of wogonin proved so far he results of studies conducted in leading laboratories around the world, making it a promising anti-cancer agent [14-19].
Our two cultures of the endemic species Scutellaria andrahnoides (callus culture and hairy root) successfully passed the procedure in the Eurasian Patent Organization and a patent was obtained for the callus culture (EA #019010 and EA #020503). According of these data, priority attention can be given to plants that synthesize flavones of wogonin group because they can be to genetic erosion by human activity. The detection of the ability of callus tissue or cultured in vitro roots of such plants will allow maintaining them to ensure their further use for active synthesis of flavones wogonin type. It can be the basis for biotechnological "production" valuable and effective compounds. The pharmacological potential of the endemic species Scutellaria andrahnoides suggests the need for using molecular biology methods for studying the flora of Kyrgyzstan, especially its endemic and rare species [22, 24]. We created at Biotechnology Institute of NAS KR supported by the Royal Botanic Gardens, Kew, which has been constantly increasing the holdings of the seed bank of Kyrgyz flora. It holds endemic and rare species (ISTC project # KR-973), which should be the basis for studying the pharmacological potential of wild plant species.
Selection of unique promising pharmacologically lines of plant roots from Kyrgyz flora, including its endemic species that are able to compete on their metabolic characteristics with known and widely used in practice species of medicinal plants.
Large mass capacity of cultures of promising lines will be available by using a laboratory bioreactor. Design and parameters of bioreactor will be specified during implementation of the proposed project. Result of work of cultivation technology of hairy roots, synthesizing valuable secondary compounds, as well as the most promising producer strains will be proposed for large-scale roots cultivation particularly to producers of medical products. This joint activity will help to develop technical documentation and a prototype of an industrial bioreactor.


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