phytochemical studies of medicinal plants in bulgaria · use of medicinal plants in bulgaria ......

Phytochemical studies of

medicinal plants in Bulgaria

Prof. Dr. Stefan Nikolov D.sci.

THE PLANTS DIVERSITY IN

BULGARIA • Bulgaria is relatively small in size 111 000 km2

but it is rich in biological diversity – 7835 species:

Algae - 3000

Lichenes - 710

Bryophyta - 660

Lycopodiophyta - 7

Equisetophyta - 12

Polypodiophyta - 30

Pinophyta - 16

Magnoliophyta - 3400

USE OF MEDICINAL PLANTS IN

BULGARIA

In the practice of folk medicine

about 500 – 600 species are used.

For the needs of pharmaceutical

industry, phytotherapy and for

export 200 species are applied more

frequently.

In Bulgaria, phytochemical studies of medicinal plants have a long history.

They have been and are still subject of scientific research units, primarily at the Institutes of BAS, Faculty of Pharmacy

Sofia, the Bulgarian pharmaceutical industry and others.

This presentation will present several examples of these studies in the Faculty

of Pharmacy in Sofia and in the Institute of Organic Chemistry with

Centre of Phytochemistry, BAS.

Department of Pharmacognosy, was one

on the first academic units established at the

Faculty of Pharmacy – Sofia, 65 years ago.

Since then, the discovery and

characterization of biological active

phytochemicals has been the most important

field of scientific research at the

Department.

Copyright © 1997 Ivo Ivanov

The attention of the colleagues from the

Department, has been focused on the following

main issues:

Isolation, purification, separation and structure elucidation of biological active compounds from medicinal plants;

Quantitative and qualitative analyses of some active substances;

Study of the content and dynamics of accumulation of some active compounds in medicinal plants;

Standardization and control of herbal drug raw material;

Other issues of interest comprise:

Biologicaly active compounds,

produced via plant cells and tissue

cultures;

Taxonomical, chorology, ecological,

biological and chemotaxonomical

characteristics of Bulgarian flora

species.

Department of Pharmacognosy

Two scientific basic topics traditionally developed at the department:

Saponins – triterpenoids and steroids and

Phenolic compounds


• Early studies on triterpene saponins

have been initiated from the founder of

the department, Prof. Dr. Asparukh

Boychinov.


• Early studies on the steroid saponins

have been initiated by prof. Dr.

Diana Panova, one of the inventors

of the famous Bulgarian drug

"Tribestan" whose active

pharmaceutical ingredient is a

saponine mixture derived from

Tribulus terrestris.


• The second topic are the phenol

compounds, namely flavonoids.

Prof. Dr. Hristo Ahtardzhiev was

the first researcher in this field in

Bulgaria. He lead the department

during the period 1966-1983.


In 1990 a Laboratory of Pharmaceutical Biotechnology has been founded at the Department

The main activities are focused on elaboration and optimization of methods for biotechnological production of saponins, and phenol compounds /e.g. flavonoids, lignans, etc./


In order to identify new saponins

and phenolic compounds (phenolic

acids, xanthones, catechins,

flavonoids) many species of plant

genera and dozens of families from

the Bulgarian and foreign flora have

been explored at the department.

Department of Pharmacognosy Classic and state-of-the-art chromatography

methods are most often used for isolation, purification and separation of compounds from the plants.

The compounds are identified by the following methods:

melting point;

spectral (IR, UV, EI-MS, FAB-MS, H1 and C13 and other modern NMR methods);

Chemical (hydrolysis, acetylation and methylation).

Department of Pharmacognosy Using these methods steroid saponins,

sapogenins and sterols were identified from the

following species of the genera Asparagus and

Ruscus (Liliaceae):

Asparagus maritimus (L.) Mill.

Asparagus verticillatus L.

Ruscus aculeatus L.

Ruscus ponticus Woronow

Ruscus hypoglossum L.


Triterpenoid saponins were isolated,

purified, separated and identified as

new natural compounds from plant

species of the genus Astragalus

(Fabaceae), Gypsophyla

(Caryophyllaceae), Chenopodium

(Chenopodiaceae).


Phenolic compounds were isolated, purified, separated and identified as new

natural compounds from plant species of the genus: Hypericum (Guttiferae), Gentiana (Gentianaceae), Malaleuca (Myrtaceae), Stellaria (Caryophyllaceae), Ferulago

(Apiaceae), Platycodon (Campanulaceae), Astragalus (Fabaceae), Potentilla

(Rosaceae), Achyranthes (Amaranthaceae), Scleranthus (Caryophyllaceae), Pulsatilla

(Ranunculaceae).

•


Through genetic transformation in plants‘ sells of Astragalus, Althea, Datura, Hyosciamus and Linum,

species cell and tissue cultures have been prepared, allowing high yield

production of new biologically active compounds. New technologies for

their bioreactor cultivation have also been developed.


• It is important to note, that the phytochemical investigations are not ends in themselves.

• There has always been an emphasize on the biological activity of the compounds that have been isolated and elucidated, some of which have been found to be novel compounds.


There have been several research projects aimed at bioactivity-guided fractionation and identification of phytochemicals with

antineoplastic activity, in collaboration with the department of Phrmacology.

For example saponins from Astragalus corniculatus Bieb., Fabaceae,

pholoroglucinols from Hypericum species, diverse phenolic compounds (e.g. flavonoids,

benzophenones, xanthones, etc.)


Astragalus corniculatus Bieb., Fabaceae


• Three novel triterpenoid saponins have been identified from the species:

3-O-β-[4-oxo-β-pentopyranosyl-(1→2)-β-D-glucopyranosyl]-21 -hydroxy oleanolic acid;

3β-4-oxo-β-pentopyranosyl-21 - hydroxy oleanolic acid;

3-O-β-D-xylopyranosyl-3β,19 -–dihydroxyоlеаn-12-ene-28, 21β–olide


COOH

OH

O

O

H

HO

H

HO

H

H

H

OH

O

H

HO

H

H

OH

OO

H

H

3-O-β-[4-oxo-β-pentopyranosyl-(1→2)-β-D-glucopyranosyl]-

21 -hydroxy oleanolic acid Krasteva, I., S. Nikolov, M. Kaloga, G. Mayer. Triterpenoid saponins from

Astragalus corniculatus. Z. Naturforsch., 61b, 2006, 9, 1166-1169. IF2006=0.825


COOH

OH

OO

H

HO

H

H

OHH

HO

3β-4-oxо-β-pentopyranosyl-21 - hydroxy oleanolic acid

Krasteva, I., S. Nikolov, M. Kaloga, G. Mayer. Triterpenoid saponins from Astragalus corniculatus. Z. Naturforsch., 61b, 2006, 9, 1166-1169. IF 0.825


HO O

C

O

HH

HO

H

HO

H

HO

H

H

OHH

H

O

Krasteva, I., S. Nikolov, M. Kaloga. A new saponin lactone from Astragalus

corniculatus. Natural Product Research, 21, 2007, 10, 941-945. IF 0.683

3-O-β-D-xylopyranosy-3β,19 -dihydroxyоlеаn, 21β–olide

In the Department of Immunology,

Institute of Experimental Pathology

and Parasitologi, BAS, was studied

purified saponin mixture from

Astragalus corniculatus containing

mainly these three new triterpene

saponins as was proven strong

immunomodulating and

immunostimulating effect.

Migration area (mm2) of peritoneal

macrophages from normal and tumor bearing

hamsters treated w ith PSM

0

0.5

1

1.5

2

2.5

3

3.5

7 14 21

days

mig

ratio

n (

mm

2)

Sap+TTSapControl

0

0,2

0,4

0,6

0,8

1

1,2

1,4

1,6

PSM+T T PSM Control

Mortality percent in Graffi tumor bearing hamsters treated

with PSM

0

20

40

60

80

100

120

28 30 32 35 40

days after tumor transplantation

perc

ent

mort

alit

y

T +PSM 1

T +PSM 2

T

Toshkova, R. A., I. N. Krasteva, D.W. Wesselinova, I. Ivanov, S. D. Nikolov. Influence of

purified saponin mixture from Astragalus corniculatus Bieb. on phagocytic cells in Graffi tumor

bearing hamsters. Journal of Ethnopharmacology, 109, 2007, 3, 394-399. IF 2.049

Toshkova, R. A., I. N. Krasteva, S. D. Nikolov. Immunorestoration and augmentation of mitogen

lymphocyte response in Graffi tumor bearing hamsters by purified saponin mixture from

Astragalus corniculatus. Phytomedicine, 15, 2008, 10, 876-881. IF 2.330

The DepartmentThe Department Natural Product Natural Product Chemistry has been a part of the Chemistry has been a part of the

Institute of Organic Chemistry since its Institute of Organic Chemistry since its

opening in 1968.opening in 1968.

Natural ProductsNatural Products

•• Characterization of the chemical diversity Characterization of the chemical diversity and health promoting potential of Bulgarian and health promoting potential of Bulgarian floraflora

•• Isolation of new biologically active natural Isolation of new biologically active natural compounds (alkaloids, compounds (alkaloids, terpenoidsterpenoids, flavonoids , flavonoids and other and other phenolicsphenolics))

•• Development of methods for Development of methods for standardization and quality control of standardization and quality control of Bulgarian medicinal plants and propolis Bulgarian medicinal plants and propolis

Sesquiterpene Lactones and Other Sesquiterpene Lactones and Other PhytochemicalsPhytochemicals in in AsteraceaenAsteraceaen

Plants: New compounds, bioactivity, Plants: New compounds, bioactivity, analysis, chemotaxonomyanalysis, chemotaxonomy

•• AnthemisAnthemis

•• AchilleaAchillea

•• ArtemisiaArtemisia

•• TanacetumTanacetum

•• XanthiumXanthium

Over 35 publications in the last 20 yearsOver 35 publications in the last 20 years

Propolis researchPropolis research

•• Chemical composition of propolis from Chemical composition of propolis from different locationsdifferent locations

•• Biologically active constituents from Biologically active constituents from propolispropolis

•• New propolis types: Mediterranean New propolis types: Mediterranean propolis (With the group of Prof. propolis (With the group of Prof. HinouHinou))

•• Standardization of poplar propolisStandardization of poplar propolis


Alkaloids: structure, analysis, Alkaloids: structure, analysis, chemical chemical transfromationstransfromations and and

biological activitybiological activity

•• ThalictrumThalictrum

•• BerberisBerberis

•• PapaverPapaver

•• DaturaDatura

•• IsopyrumIsopyrum

•• Potent antiviral Potent antiviral substance:oxoglaucinsubstance:oxoglaucin


Other important subjectsOther important subjects•• TribulusTribulus terrestristerrestris: : new bioactive new bioactive

constituents, analysis and standardizationconstituents, analysis and standardization

•• Essential oils of Bulgarian aromatic plantsEssential oils of Bulgarian aromatic plants

•• SideritisSideritis: chemical constituents, biological : chemical constituents, biological activityactivity

•• IridoidsIridoids and and flavonoidsflavonoids from Bulgarian from Bulgarian medicinal plants: medicinal plants: LamiaceaeLamiaceae, , ScrofulariaceaeScrofulariaceae

•• Modern methods for extraction of bioactive Modern methods for extraction of bioactive compounds from plant materialcompounds from plant material

•• PhytochemicalPhytochemical studies of Black Sea algae studies of Black Sea algae

The Balkan region is rich in endemic species and is one of the most

important centers of plant biodiversity in Europe.

Therefore, responsibility and obligation of every Bulgarian

phytochemists is to explore the Bulgarian flora as a source of new

biologically active structures.

Thank you for your attention !

phytochemical studies of medicinal plants in bulgaria · use of medicinal plants in bulgaria ......

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