Ispitivanje sekundarnih metabolita i farmakološke aktivnosti odabranih vrsta roda Hieracium L. (Asteraceae) sa Balkanskog poluostrva

Abstract

hibridogenih).Semipreparativnim LC-MS metodama, iz MeOH ekstrakta cvasti H. calophyllum izolovana sučetiri seskviterpenska laktona (krepizid E i tri nova jedinjenja: 8-epi-ikserisamin A, kalofilamin A ikalofilamin B), a iz MeOH ekstrakta podzemnih organa H. scheppigianum pet fenolkarboksilnih(mono- ili di-O-kafeoilhina) kiselina (identifikacija na osnovu NMR i MS spektara).Ukupno četiri seskviterpenska laktona, sedam mono- ili di-O-kafeoilhina kiselina i 19flavonoida (luteolin, apigenin, diosmetin, 15 njihovih heterozida i heterozid kvercetina)kvantifikovani su u suvim MeOH ekstraktima ispitivanih podzemnih organa dve vrste i herbi 28vrsta LC-MS metodama, i pet triterpena (derivata ursana, oleana i lupana) u suvim CH2Cl2ekstraktima herbi 28 vrsta GC-FID-MS metodom (identifikacija pomoću standarda, NMR, MS i/iliUV spektara). Hemosistematski značaj jedinjenja identifikovanih u herbama 28 vrsta utvrđen jemultivarijantnim statističkim metodama (PCA, nMDS i UPGMA).Suvi MeOH ekstrakti herbi su in vitro pokazali značajan ukupni antioksidantni potencijal isposobnost neutralizacije slobodnih DPPH•, ABTS•+ i OH• radikala (28 vrsta) i inhibicijeacetilholinesteraze (27 vrsta) i butirilholinesteraze (7 vrsta). Među testiranih 12 jedinjenja, najboljuantiholinesteraznu aktivnost ispoljila su tri flavonoidna aglikona i 8-epi-ikserisamin A. Odabranisuvi MeOH i CH2Cl2 ekstrakti herbi šest vrsta pokazali su antimikrobnu aktivnost prema 18, a 8-epi-ikserisamin A i krepizid E prema 4 mikroorganizma. Isti odabrani izolati ispoljili sucitotoksični efekat prema tri, odnosno jednoj tumorskoj ćelijskoj liniji, uz zanemarljivu inhibicijurasta zdravih ćelija. Tri odabrana MeOH i CH2Cl2 ekstrakta su u modelu inflamacije šape pacovaizazvane karageninom pokazala antihiperalgezijsku, ali ne i antiedematoznu aktivnost; bezbednostprimene dva ekstrakta koji su ispoljili značajnu antihiperalgezijsku aktivnost pokazana je in vivorotarod i testom akutne toksičnosti.Ključne reči:

nonhybridogenousand 16 hybridogenous).Using semipreparative LC-MS methods, four sesquiterpene lactones (crepiside E and three newcompounds: 8-epiixerisamine A, calophyllamine A and calophyllamine B) were isolated from theMeOH extract of H. calophyllum flowering heads, and five phenolic (mono- or di-Ocaffeoylquinic)acids from the MeOH extract of H. scheppigianum underground parts(identification based on NMR and MS spectra).Total of four sesquiterpene lactones, seven mono- or di-O-caffeoylquinic acids and 19flavonoids (luteolin, apigenin, diosmetin, their 15 glycosides and one quercetin glycoside) werequantified in the dried MeOH extracts of the investigated underground parts of two species andherbs of 28 species, using LC-MS methods, and five triterpenes (ursane, oleane and lupanederivatives) in the dried CH2Cl2 extracts of the herbs of 28 species, using GC-FID-MS method(identification using standards, NMR, MS and/or UV spectra). Chemosystematic significance ofthe compounds identified in the herbs of 28 species was determined using multivariate statistics(PCA, nMDS and UPGMA).Dried MeOH herb extracts in vitro exhibited significant total antioxidant activity andscavenging of DPPH•, ABTS•+ and OH• radicals (28 species), as well as the ability to inhibitacetylcholinesterase (27 species) and butyrylcholinesterase (7 species). Among 12 testedcompounds, three flavonoid aglycones and 8-epiixerisamine A exhibited the highestanticholinesterase activity. Selected dried MeOH and CH2Cl2 herb extracts of six species showedantimicrobial activity against 18, whereas 8-epiixerisamine A and crepiside E against fourmicroorganisms. The same selected isolates exhibited cytotoxic activity against three and onecancer cell lines, respectively, with negligible inhibition of the normal cells growth. In thecarrageenan-induced localized inflammation model in rats, three selected MeOH and CH2Cl2extracts exhibited antihyperalgesic, but not antiedematous activity; safety of the oral administrationof two extracts that exhibited significant antihyperalgesic activity was demonstrated in vivo inrotarod test and acute oral toxicity study.