Biološka aktivnost ekstrakata komercijalnih lekovitih biljaka familije Lamiaceae iz Srbije
Biological activity of commercial medicinal Lamiaceae plant extracts from Serbia
Author
Oalđe Pavlović, MarianaMentor
Rajčević, NemanjaCommittee members
Vuković-Gačić, BrankaAlimpić Aradski, Ana
Božić Nedeljković, Biljana
Marin, Petar
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Show full item recordAbstract
Čovekova potraga za terapeutskim sredstvima prirodnog, a posebno biljnog porekla, datira
još iz starih vremena. Sa napretkom savremene nauke omogućeno nam je da detaljno istražujemo
njihove fitokonstituente, biološku aktivnost i mehanizme delovanja, sa ciljem dobijanja
bezbednijih i efikasnijih farmakoloških agenasa.
Cilj ove doktorske disertacije je bio određivanje hemijskog sastava i biološke aktivnosti
metanolnih, etanolnih i vodenih ekstrakata 18 vrsta familije Lamiaceae koje se tradicionalno
upotrebljavaju i komercijalno gaje u Srbiji.
Hemijska karakterizacija je urađena korišćenjem spektrofotometrijskih metoda
(određivanjem ukupnog sadržaja fenola, fenolnih kiselina, flavonoida, flavonola, kumarina i
triterpena), kao i HPLC-DAD analizom. Biološki potencijal pomenutih ekstrakata je određen
testiranjem njihove antioksidativne, genoprotektivne, antigenotoksične, antidijabetične,
antineurodegenerativne, antineuroinflamatorne, antitumorske i antibakterijske aktivnosti, kao i
procenom ...njihovog uticaja na modelu zarastanja rane.
Ekstrakti ispitivanih predstavnika familije Lamiaceae obiluju sekundarnim metabolitima,
posebno onima iz grupe fenolnih jedinjenja, pri čemu sastav i količina komponenti zavisi od
primenjenog rastvarača za ekstrakciju. U ovim ekstraktima, najprisutnija fenolna kiselina je bila
rozmarinska kiselina, a najprisutniji flavonoid, flavon luteolin-7-O-glukozid.
Iako su svi ekstrakti ispoljili antioksidativnu aktivnost, najjači potencijal su imali ekstrakti
Origanum vulgare i Melissa officinalis. Vodeni ekstrakti su pružali najviši nivo zaštite plazmidne
DNK, posebno ekstrakti Mentha × piperita i Thymus vulgaris. Dok su najjaču antigenotoksičnu
aktivnost u prokariotskom modelu imali etanolni ekstrakti Rosmarinus officinalis i Salvia
officinalis, na eukariotskom modelu posebno dobru aktivnost su pokazali ekstrakti Hyssopus
officinalis, Leonurus cardiaca i Marrubium vulgare. Iako ekstrakti nisu inhibirali aktivnost enzima
α-amilaze, svoju antidijabetičnu aktivnost su ispoljili inhibicijom aktivnosti α-glukozidaze, pri
čemu su se posebno izdvojili vodeni ekstrakti M. piperita, Satureja montana i Thymus serpyllum.
Ispitivani ekstrakti imaju dobar antineurodegenerativni potencijal procenjivan inhibitornim
efektom na aktivnost acetilholinesteraze tirozinaze, kao i antineuroinflamatorni i
antineurocitotoksični efekat prema LPS-om aktiviranim ćelijama mikroglije. Većina ispitivanih
etanolnih ekstrakata je imala antitumorski efekat prema ćelijskoj liniji kolorektalnog kancera.
Genotoksični potencijal prema ovim tumorskim ćelijama koji je bio sličan efektu etopozida je
ispoljio jedino etanolni ekstrakt Ocimum basilicum. Ekstrakti su imali i antibakterijski potencijal:
inhibirali su rast testiranih bakterijskih sojeva, posebno gram-pozitivnih, inhibirali su invaziju
Pseudomonas aeruginosa PAO1 prilikom infekcije fibroblasta pluća i formiranje biofilma P.
aeruginosa PAO1, a takođe su degradirali i već formirani biofilm P. aeruginosa PAO1, pri čemu su
se posebno izdvojili ekstrakti S. montana i O. vulgare.
U ovoj doktorskoj disertaciji je po prvi put testirana i potvrđena genoprotektivna, kao i
antigenotoksična aktivnost ispitivanih ekstrakata, a takođe po prvi put daje uvid u
antineuroinflamatornu i antitumorsku aktivnost pojedinih predstavnika familije Lamiaceae. Na
osnovu IBR analize svih ekstrakata predstavnika familije Lamiaceae, najbolji ukupni biološki
potencijal su imali O. vulgare i M. officinalis, kao i etanolni ekstrakt S. officinalis, dok su najniži
biološki potencijal pokazali ekstrakti M. vulgare, kao i etanolni ekstrakt G. hederacea.
The man's search for natural therapeutic agents, especially those of plant origin, dates
back to ancient times. However, with the progress of modern science, we have been able to
investigate in detail their phytoconstituents, biological activity and mechanisms of action in the
human body, in order to obtain safer and more effective farmaceuticals.
The aim of this dissertation was to determine the chemical composition and biological
activity of methanolic, ethanolic and aqueous extracts of 18 species of the Lamiaceae family that
are being traditionally used and commercially grown in Serbia.
Chemical characterization was performed using spectrophotometric methods (by the
determination of the total content of phenols, phenolic acids, flavonoids, flavonols, coumarins, and
triterpenes), as well as by HPLC-DAD analysis. The biological potential of the extracts was
determined by testing their antioxidant, genoprotective, antigenotoxic, antidiabetic,
antineurodegenerative, antineuro-inflammato...ry, antitumor, and antibacterial activities, as well as
by assessing their influence on wound healing.
The extracts of the tested Lamiaceae representatives are rich in secondary metabolites,
mainly phenolic compounds. However, the content and amount of phytocomponents depends on
the extraction solvent. In these extracts, the dominant phenolic acid was rosmarinic acid, and the
dominant flavonoid was flavone luteolin-7-O-glucoside.
Although all extracts showed antioxidant activity, Origanum vulgare and Melissa officinalis
had the highest antioxidant potential. Aqueous extracts provided the highest plasmid DNA
protection, especially Mentha × piperita and Thymus vulgaris. While the ethanolic extracts of
Rosmarinus officinalis and Salvia officinalis had the strongest antigenotoxic activity in the
prokaryotic model, Hyssopus officinalis, Leonurus cardiaca, and Marrubium vulgare extracts
showed excellent activity in the eukaryotic model. Although the extracts had no effect on α-
amylase inhibition, they exhibited antidiabetic activity by inhibiting the activity of α-glucosidase,
especially aqueous extracts of M. piperita, Satureja montana and Thymus serpyllum. The tested
extracts possess antineurodegenerative potential, which they exhibit by inhibiting the activities of
acetylcholinesterase and tyrosinase, as well as antineuroinflammatory and antineurocytotoxic
potentials against LPS-activated microglia. Most of the ethanolic extracts had an antitumor effect
on colorectal cancer cells, while only the genotoxic effects of Ocimum basilicum were similar to
etoposide. The extracts, especially S. montana and O. vulgare, exhibited their antibacterial
potential by inhibiting the growth of tested bacterial strains, especially gram-positive ones, by
inhibiting Pseudomonas aeruginosa PAO1 invasion during human lung fibroblast infection, as well
as biofilm formation inhibition and degradation of already formed P. aeruginosa PAO1 biofilm.
In this dissertation, the genoprotective and antigenotoxic activities of the examined plant
extracts were tested and confirmed for the first time. Moreover, this study provides the first
insight into the antineuroinflammatory and antitumor activities of certain investigated Lamiaceae
representatives. Based on the IBR analysis of all tested Lamiaceae extracts, O. vulgare and M.
officinalis, as well as ethanolic extract of S. officinalis had the best overall biological potential,
while extracts of M. vulgare and ethanolic extract of G. hederacea showed the lowest biological
potential.