L’apparition de plusieurs maladies, telles que le cancer, le diabète, l'hypertension artérielle et la propagation d'infections de type virus mutagènes peuvent être liées à la qualité et au mode de vie que nous menons aujourd’hui. En effet, plusieurs études sur les facteurs déclenchant ces maladies dites "morbides" à long ou à court terme, sont liées au stress et à la qualité des aliments consommés, qu'ils soient d'origine végétale ou animale. Ces maladies deviennent un phénomène courant, elles touchent différentes races et toutes les catégories de la société. D'après les recherches ethnobotaniques, les substances d’origine naturelle, ont permis à des civilisations de survivre à des maladies mortelles. A titre d'exemple, on retrouve ainsi des références à des périodes de fièvre paludique en Chine et à des symptômes de cette maladie dans le «Huangdi Neijiang» Le Canon de Médecine datant des environs du premier siècle avant notre ère, plus de 2000 ans, qui relate de l'emploi de plantes médicinales, pour soulager les fièvres (Desgrouas et al., 2014).Vers 186 avant J.-C. apparaît, dans certaines régions de Chine, l'utilisation en tisane, du Qing hao su, appelé plus tard artémisinine en Occident et extrait d'une plante médicinale utilisée comme antipyrétique appelée "Qing hao", Artemisia annua ou Armoise annuelle. L'artemisinine bloque une enzyme qui permet au parasite de pomper le calcium et l'empêche ainsi de se développer. Au jour d'aujourd'hui l’Artemisinin-based combination therapy, en français Thérapie combinée à base d'artémisinine et en sigle ACT, est une thérapie et une prévention tertiaire dans les cas de paludisme simple.Dans cette optique notre étude vient s'ajouter à une longue série d'études menées sur les plantes médicinales et les substances naturelles extraites. Elle a pour objectif de révéler de nouvelles biomolécules, de mettre en évidence leurs activités biologiques grâce à des techniques de biotechnologies d'une part. D'autre part ces investigations permettront de valoriser les ressources naturelles qui se distinguent par leur endémicité.Pour se faire, notre choix s'est porté sur deux plantes médicinales endémiques à l'Algérie Cyclamen africanum Boiss. & Reuter et Zygophyllum cornutum Coss. , après une recherche ethnobotanique sur la pharmacopée traditionnelle du Nord de l'Afrique, et qui a révélé l’efficacité de ces plantes dans les problèmes inflammatoires minimes chez les autochtones, nous avons entrepris des investigations pharmaco- biochimiques.Ces dernières nous ont permis d'isoler : cinq composés à partir de l'extrait méthanolique des racines de l'espèce Cyclamen africanum Boiss. & Reuter, deux nouvelles saponines triterpéniques de type Oleanane, Afrocyclamin A et B (1, 2), ainsi que trois saponines triterpénoïdes connus sous le nom de lysikokianoside (3), deglucocyclamin I (4) et de son dérivé d'acide dicrotalique (5); et Sept saponosides connus à partir de l'extrait méthanolique de la plante entière de Zygophyllum cornutum Coss., ces saponosides sont de type ursane, ce type de triterpène est rapporté dans cette espèce pour la première fois et peuvent être considérés comme un marqueur chimio-taxonomique (chemotype) du genre Zygophyllum. Les structures ont été élucidées, sur la base de l'analyse des spectres de l'expérience RMN-1D et RMN- 2D (COSY, TOCSY, NOESY, HMBC et HSQC) et spectrométrie de masse en source FAB mode ion négatif. Des activités biologiques, des fractions saponosidiques Fr.1 et Fr.2, ont été testées sur des lignées de Rats mâles et femelles, de la race Winstar pour évaluer l'activité anti inflammatoire.La fraction saponosidique Fr.1 de Cyclamen africanum à la dose 5 mg, a montré un effet significatif sur l'inflammation causé par la carragénine, en réduisant l'oedème et la réponse immunitaire, qui s'est traduite par la concentration des protéines de la réponse inflammatoire (PRI) à travers leurs action sur les pro-médiateurs de l'inflammation (COX-2, PGE2, TNF -α, iNOS). / The appearance of several diseases, such as cancer, diabetes, high blood pressure and spread of infections mutagenic virus type can be linked to the quality and lifestyle that we lead today. Indeed, several studies on the factors triggering these so-called "morbid" long-or short-term illnesses are related to stress and quality of food consumed, whether of plant and animal origin. These diseases are becoming a common occurrence, they affect different races and all classes of society. According ethnobotanical research, naturally occurring substances, allowed civilizations to survive deadly diseases. For example, we thus find references to periods of malarial fever in China and one of the symptoms of this disease in the "Huangdi Neijiang" The Canon of Medicine dating from around the first century BC, more than 2000 years, which relates to the use of herbal medicines to relieve fevers (Desgrouas et al., 2014).Around 186 BC appears, in some parts of China, the use in herbal tea, Qing hao su, later known as artemisinin in the West and extracted from a medicinal plant used as antipyretic called "Qing hao" Artemisia annua or annual wormwood. Artemisinin blocks an enzyme which enables the parasite to pump calcium and prevents it from developing. As of today the Artemisinin-based combination therapy in French Combination therapy of artemisinin and ACT acronym, is a therapy and tertiary prevention in cases of uncomplicated malaria.From this perspective our study adds to a long series of studies on medicinal plants and natural substances extracted. It aims to reveal new biomolecules, highlighting their biological activities through techniques of biotechnology on the one hand. Moreover, these investigations will develop natural resources that are characterized by endemic.To do this, our choice is focused on two endemic medicinal plants in Algeria Cyclamen africanum Boiss. & Reuter and Zygophyllum cornutum Coss. After an ethnobotanical research on traditional medicine in Northern Africa, which showed the effectiveness of these plants in minimal inflammatory problems among Aboriginal, we undertook biochemical pharmacological investigations.The latter allowed us to isolate, five compounds from the methanol extract of the roots of the species Cyclamen africanum Boiss. Reuter & two new oleanane triterpene saponins type, Afrocyclamin A and B (1, 2) and three triterpenoid saponins known lysikokianoside of (3), deglucocyclamin I (4) and its derivative dicrotalique acid (5) September and known from the methanol extract saponins from the whole plant of Zygophyllum cornutum Coss. these saponins are ursane type, type triterpenes are reported in this species for the first time and can be considered a chemotherapy marker Taxonomic (chemotype) of Zygophyllum kind. The structures were elucidated on the basis of the analysis of NMR spectra of the experience-1D and 2D-NMR (COSY, TOCSY, NOESY, HSQC and HMBC) and mass spectrometry method negative ion FAB source. The biological activities of saponosidiques FR.1 and Fr.2 fractions were tested on lines of male and female rats of the Winstar rats to evaluate the anti-inflammatory activity. The saponosidique fraction FR.1 Cyclamen africanum the 5 mg dose, showed a significant effect on inflammation caused by carrageenan, reducing edema and immune response, which resulted in the concentration of protein the inflammatory response (PRI) through their action on the pro-inflammatory mediators (COX-2, PGE2, TNF -α, iNOS). The fraction of Fr.2 saponosidique Zygophyllum dose 20 mg did not show a significant effect on inflammation in general.

<p>U ovoj doktorskoj disertaciji prikazani su rezultati istraživanja 15&nbsp;vrsta&nbsp; biljaka&nbsp; koje&nbsp; pripadaju&nbsp; rodovima <em>Rumex,&nbsp; Polygonum,&nbsp;Bistorta,&nbsp; Persicaria i&nbsp; Fagopyrum,</em>&nbsp; podfamilije&nbsp; Polygonoideae,&nbsp;familije&nbsp; Polygonaceae,&nbsp; sakupljenih&nbsp; na&nbsp; teritoriji&nbsp; centralnog&nbsp; i&nbsp;zapadnog &nbsp;Balkana u periodu od 2009-2011. godine. Sprovedena&nbsp;istraživanja&nbsp; su&nbsp; se&nbsp; odvijala&nbsp; u&nbsp; dva&nbsp; pravca:&nbsp; fitohemijska&nbsp; i&nbsp;biohemijsko-biolo&scaron;ka&nbsp; ispitivanja.&nbsp; Predmet&nbsp; analiza&nbsp; bili&nbsp; su&nbsp;ekstrakti&nbsp; herbi&nbsp; i&nbsp; rizoma&nbsp; ispitivanih&nbsp; biljaka.&nbsp; Fitohemijska&nbsp;ispitivanja&nbsp; obuhvatila&nbsp; su,&nbsp; pored&nbsp; spektrofotometrijskog&nbsp;određivanja&nbsp; ukupnih&nbsp; fenola,&nbsp; ukupnih&nbsp; flavonoida&nbsp; i&nbsp; ukupnih&nbsp;antrahinonskih jedinjenja, i određivanje sadržaja 51 komponente&nbsp;iz standardne sme&scaron;e različitih klasa fenolnih jedinjenja LC-MSMS&nbsp; metodom,&nbsp; odnosno &nbsp;hromatografsko&nbsp; profilisanje&nbsp; ekstrakata&nbsp;LC-DAD-MS&nbsp; metodom.&nbsp; Odabirom&nbsp; nekoliko&nbsp; različitih&nbsp; model&nbsp;sistema&nbsp; za&nbsp; merenje&nbsp; antioksidantne&nbsp; aktivnosti&nbsp; (neutralizacija&nbsp;DPPH&nbsp; radikala,&nbsp; redoks&nbsp; kapacitet&nbsp; -&nbsp; FRAP&nbsp; test,&nbsp; skevindžer&nbsp;aktivnost&nbsp; prema&nbsp; superoksidanjon&nbsp; radikalu,&nbsp; NO&nbsp; radikalu&nbsp; i&nbsp; OH&nbsp;radikalu,&nbsp; kao&nbsp; i&nbsp; inhibicija&nbsp; lipidne&nbsp; peroksidacije)&nbsp; procenjen&nbsp; je&nbsp;antioksidantni&nbsp; potencijal&nbsp; ekstrakata,&nbsp; dok&nbsp; je&nbsp; za&nbsp; procenu&nbsp; njihove&nbsp;antiinflamatorne&nbsp; aktivnosti&nbsp; kori&scaron;ćen&nbsp; potencijal&nbsp; inhibicije&nbsp;biosinteze medijatora inflamacije u humanim trombocitima (kao&nbsp;model&nbsp; sistemu).&nbsp; Mikrobiolo&scaron;ka&nbsp; ispitivanja&nbsp; su&nbsp; obuhvatila&nbsp;određivanje&nbsp; potencijala&nbsp; ovih&nbsp; vrsta&nbsp; u&nbsp; inhibiciji&nbsp; rasta&nbsp; serije&nbsp; gram&nbsp;pozitivnih i gram negativnih sojeva batkerija. Konačno, urađena&nbsp;je&nbsp; analiza&nbsp; korelacije&nbsp; hemijskog&nbsp; sastava,&nbsp; biolo&scaron;ke&nbsp; aktivnosti&nbsp; i&nbsp;pripadnosti taksonomskim grupama.</p> / <p>Phytochemical&nbsp; and&nbsp; biochemical&nbsp; analysis&nbsp; of&nbsp; herbal&nbsp; and&nbsp; root&nbsp;ethanol&nbsp; extracts&nbsp; of&nbsp; 15&nbsp; species&nbsp; belonging&nbsp; to&nbsp; different&nbsp; genera&nbsp;(<em>Rumex,&nbsp; Polygonum,&nbsp; Bistorta,&nbsp; Persicaria and&nbsp; Fagopyrum</em>)&nbsp; of&nbsp;subfamily&nbsp; Polygonoideae,&nbsp; was&nbsp; examined.&nbsp; Phytochemical&nbsp;characterization&nbsp; included&nbsp; spectrophotometric&nbsp; determination&nbsp; of&nbsp;total&nbsp; phenolic,&nbsp; total&nbsp; flavonoids&nbsp; and&nbsp; total&nbsp; anthraquinone&nbsp; contents,&nbsp;quantification&nbsp; of&nbsp; 51&nbsp; secondary&nbsp; metabolites&nbsp; by&nbsp; LC/MS/MS&nbsp;analysis&nbsp; and&nbsp; chromatographic&nbsp; fingerprinting by&nbsp; LC/DAD/MS&nbsp;technique,&nbsp; of&nbsp; prepared&nbsp; extracts.&nbsp; The&nbsp; antioxidant&nbsp; activity&nbsp; was&nbsp;evaluated&nbsp; by&nbsp; measuring&nbsp; ferric&nbsp; reducing&nbsp; ability&nbsp; (FRAP)&nbsp; of&nbsp; the&nbsp;extracts and their radical scavenging capacity towards DPPH, OH,&nbsp;NO and O₂^{&ndash;&nbsp;}radicals, and inhibition of lipid peroxidation). Antiinflammatory activity was evaluated by LC/MS/MS monitoring of&nbsp;selected&nbsp; metabolites&nbsp; (12-(S)-HHT,&nbsp; 12(S)-HETE,&nbsp; PGE_2&nbsp;,&nbsp; PGF_2&alpha;,&nbsp;and TXB₂) formed in cyclooxygenase and lipoxygenase pathways&nbsp;of arachidonic acid metabolism. Human platelets were used as a&nbsp;source&nbsp; of&nbsp; enzymes,&nbsp; while&nbsp; inflammation&nbsp; was&nbsp; induced&nbsp; by&nbsp;calcimycin. The antibacterial activity of prepared&nbsp; extracts against&nbsp;nine&nbsp; bacterial&nbsp; strains&nbsp; was&nbsp; evaluated&nbsp; by&nbsp; microtiter&nbsp; assay&nbsp; with&nbsp;resazurin as a colorimetric growth indicator.</p>

<p>U ovoj doktorskoj disertaciji ispitan je hemijski sastav i biolo&scaron;ke aktivnosti<br />ekstrakata deset&nbsp; samoniklih&nbsp; taksona roda&nbsp; <em>Allium</em>&nbsp; sect.&nbsp;<em> Codonoprasum:&nbsp; A. carinatum</em>&nbsp;subsp. <em>pulchellum,&nbsp; A. carinatum&nbsp;</em> subsp. <em>carinatum,&nbsp; A. fuscum&nbsp;</em> var. <em>gracile,&nbsp; A. fuscum&nbsp;</em> var.&nbsp;<em>fuscum,&nbsp; A. flavum</em> subsp. <em>flavum,&nbsp; A. melanantherum,&nbsp; A. paniculatum&nbsp;</em> subsp.&nbsp;<em> marginatum,&nbsp;A. pallens</em>&nbsp; subsp. <em>tenuiflorum,&nbsp; A. oleraceum&nbsp; </em>i&nbsp;<em> A. rhodopeum</em>, sakupljenih na&nbsp; 27 lokaliteta&nbsp;u Srbiji. Cilj rada bio je da se dobiju podaci o sadržaju biolo&scaron;ki aktivnih jedinjenja u&nbsp;ovim, do sada veoma malo ispitanim vrstama roda&nbsp; <em>Allium</em>, i utvrdi njihova potencijalna&nbsp;lekovita vrednost.</p><p>Analiza hemijskog sastava obuhvatila je: analizu volatilnih komponenti svežih&nbsp;<br />lukovica primenom headspace GC-MS tehnike, kvalitativnu analizu metanolnih &nbsp;<br />ekstrakata primenom tečnohromatografskih metoda (LC-DAD-MS i LC-MS-MS), &nbsp;<br />kvantitativnu analizu odabranih fenolnih jedinjenja LC-MS-MS tehnikom,&nbsp; određivanje&nbsp;sadržaja ukupnih&nbsp; monomernih&nbsp; antocijana&nbsp; i određivanje aktivnosti aliinaze. Ispitivanja&nbsp;biolo&scaron;kih aktivnosti ekstrakata obuhvatila su: određivanje antioksidantne,&nbsp;antiinflamatorne, antimikrobne, antimutagene i genotoksične aktivnosti, kao i ispitivanje&nbsp;uticaja na rast zdravih i tumorskih ćelija i sposobnosti indukcije ćelijske smrti.&nbsp;</p><p>Sumiranjem dobijenih rezultata može se zaključiti da ispitivani predstavnici roda&nbsp;<br /><em>Allium&nbsp;</em> sect.&nbsp; <em>Codonoprasum&nbsp;</em> predstavljaju bogate izvore biolo&scaron;ki aktivnih jedinjenja sa&nbsp;&scaron;irokim spektrom biolo&scaron;kih aktivnosti. Sa hemotaksonomskog aspekta značajno je da se&nbsp;dimetil-disulfid&nbsp; izdvaja kao&nbsp; najdominantnija&nbsp; i često jedina&nbsp; isparljiva komponenta, da&nbsp;ekstrakti većine vrsta&nbsp; sadrže veliku količinu flavonoida (prvenstveno derivata&nbsp;kvercetina), da se vrste&nbsp;<em> A. pallens&nbsp;</em> i&nbsp; <em>A. oleraceum</em>&nbsp; izdvajaju od ostalih po tome &scaron;to ne&nbsp;sadrže rutin&nbsp; a sadrže&nbsp; hiperozid,&nbsp; da je vrsta&nbsp;<em> A. rhodopeum</em>&nbsp; siroma&scaron;na fenolnim&nbsp;jedinjenjima i da su sve vrste, osim vrste&nbsp; <em>A.&nbsp; flavum</em>, bogate antocijanima. Aktivnost&nbsp;aliinaze je visoka u svim ispitivanim vrstama. Većina ispitivanih ekstrakata, izuzev&nbsp;ekstrakata vrsta&nbsp; <em>A. carinatum&nbsp;</em>i <em>A. melanantherum</em>, pokazala je izraženu antioksidantnu&nbsp;aktivnost, dok su ekstrakti vrsta <em>A. flavum</em>, <em>A. rhodopeum</em>, <em>A. oleraceum </em>i <em>A. paniculatum&nbsp;</em>snažni antiinflamatorni agensi. Ekstrakti ispitivanih predstavnika sect.&nbsp;<em> Codonoprasum&nbsp;</em>nisu pokazali antimikrobnu i antimutagenu aktivnost. Takođe, ovi ekstrakti nisu ispoljili&nbsp;genotoksični efekat na ćelije zdravog tkiva (izuzev slabog genotoksičnog efekta ekstrakta&nbsp;nadzemnih delova&nbsp;<em> A. flavum</em>), &scaron;to ukazuje na bezbednost upotrebe vrsta sect.&nbsp;<em>Codonoprasum&nbsp;</em> kao hrane ili u obliku lekova. Ekstrakti celih biljaka&nbsp;<em>A. paniculatum</em> i <em>A.&nbsp;rhodopeum</em>, kao i ekstrakt nadzemnih delova &nbsp;<em>A. melanantherum</em>&nbsp; pokazali su snažnu&nbsp;antiproliferativnu aktivnost sa povoljnim ne-tumor/tumor koeficijentima i indukovali&nbsp;apoptozu u tumorskim ćelijama, iz čega se može zaključiti da imaju visok potencijal&nbsp;primene u antitumorskoj terapiji.&nbsp;</p> / <p>In the present doctoral thesis the chemical composition and biological activities&nbsp; of&nbsp;<br />10 wild growing taxa of genus&nbsp; <em>Allium</em>&nbsp; sect. <em>Codonoprasum</em>&nbsp; (<em>A. carinatum&nbsp;</em> subsp.&nbsp;<br /><em>pulchellum,&nbsp; A. carinatum&nbsp;</em> subsp.&nbsp; <em>carinatum,&nbsp; A. fuscum&nbsp;</em> var.&nbsp; <em>gracile,&nbsp; A. fuscum</em>&nbsp; var.&nbsp;<br /><em>fuscum,&nbsp; A. flavum&nbsp;</em> subsp.&nbsp; <em>flavum,&nbsp; A. melanantherum,&nbsp; A. oleraceum,&nbsp; A. paniculatum</em><br />subsp. <em>marginatum, A. pallens</em> subsp. <em>tenuiflorum</em> and <em>A. rhodopeum</em>) were investigated.&nbsp;The samples were&nbsp; collected from 27 locations in Serbia. The aim of the study was to&nbsp;obtain data on the content of biologically active compounds in extracts of &nbsp;these&nbsp;unexplored species of the genus Allium and to determine their potential medicinal value.</p><p>Phytochemical caracterisation included: headspace GC-MS analysis of fresh bulb&nbsp;<br />volatiles, LC-DAD-MS and LC-MS-MS qualitative analysis of methanol extracts, LC-MS-MS quantitative analysis of 44 selected phenolic compounds in methanol extracts,&nbsp;determination of total monomeric anthocyanins content and alliinase activity. In order to&nbsp;assess the biological potential of methanol extracts, the antioxidant, anti-inflammatory,&nbsp;antimicrobial, antimutagenic, genotoxic and antiproliferative activities of &nbsp;the extracts&nbsp;were studied.</p><p>Summing up all the results obtained, it can be concluded that species of genus&nbsp;<em>Allium&nbsp;</em> sect.&nbsp; <em>Codonoprasum&nbsp;</em> are rich sources of biologically active compounds with a&nbsp;broad spectrum of biological activities. Dimethyl disulfide is the most dominant and&nbsp;often the only volatile component of most species, which is significant from&nbsp;chemotaxonomic point of view. The methanol extracts of investigated species contain&nbsp;high levels of flavonoids (primarily quercetin derivatives). Specificity of&nbsp; <em>A. pallens</em>&nbsp; and&nbsp;<em>A. &nbsp;oleraceum</em>&nbsp; extracts is that they do not contain rutin, but contain hyperoside, while&nbsp;small quantity of phenolic compounds&nbsp; is characteristic for&nbsp; <em>A. rhodopeum</em>&nbsp; extract. All&nbsp;investigated species, except of <em>A. flavum</em>, are rich in anthocyanins. Alliinase activity was&nbsp;high in&nbsp; all examined species. Most of the extracts, except&nbsp; <em>A. carinatum</em>&nbsp; and&nbsp; <em>A.&nbsp;melanantherum</em>&nbsp; extracts, express considerable antioxidant activity, &nbsp;while extracts of&nbsp;<em> A.&nbsp;flavum</em>,&nbsp; <em>A. rhodopeum</em>,&nbsp; <em>A. paniculatum</em>&nbsp; and&nbsp; <em>A. oleraceum&nbsp;</em> are potent anti-inflammatory&nbsp;agents. The investigated&nbsp; <em>Allium</em>&nbsp; extracts did not show antimicrobial and antimutagenic&nbsp;activity. Also, the extracts did not express genotoxic effect on healthy tissue cells&nbsp;(except the weak genotoxic effects of aerial parts extract of&nbsp; <em>A. flavum</em>), indicating that&nbsp;the use&nbsp; of these species as a food or as a drug is safe. Whole plant extracts of&nbsp; <em>A.&nbsp;paniculatum</em>&nbsp; and&nbsp;<em> A. rhodopeum</em>, as well as aerial parts extract of&nbsp;<em> A. melanantherum</em>&nbsp;showed strong antiproliferative activity (with a favorable &nbsp;non-tumor/tumor ratios) and&nbsp;induced apoptosis in tumor cells, suggesting that these plants have a high potential for&nbsp;application in antitumor therapy.</p>

<p>U okviru ove doktorske disertacije ispitan je hemijski sastav i biolo&scaron;ke aktivnosti metanolnih i vodenih ekstrakata odabranih samoniklih vrsta tribusa Urticeae, rod&nbsp; Urtica:&nbsp; U. <em>dioica</em>&nbsp; subsp.&nbsp; <em>dioica</em>&nbsp; var.&nbsp;<em> pubescens</em>, U.<em>&nbsp; dioica&nbsp;</em> subsp.&nbsp; <em>dioica&nbsp; </em>var.&nbsp; <em>dioica</em>&nbsp; i&nbsp; U. <em>kioviensis</em>&nbsp; i tribusa Parietarieae, rod&nbsp; Parietaria:<em>&nbsp; P. officinalis</em>,&nbsp; <em>P.</em><br /><em>lusitanica</em> L. subsp<em>. lusitanica</em>,<em> P. judaica</em> L. subsp. <em>judaica</em> i<em> P. serbica</em>. Cilj rada bio je da se odredi sadrţaj biolo&scaron;ki aktivnih jedinjenja u ovim, do sada veoma malo ispitanim vrstama famijije Urticaceae, i utvrdi njihov potencijal primene kao pomoćnih lekovitih sredstava i dodataka ishrani.<br />Hemijski sastav ekstrakata ispitivanih vrsta određen je primenom: tečnohromatografskih tehnika (LC-DAD-MS i LC-MS-MS) za kvalitativnu analizu metanolnih ekstrakata, dok je za kvantitativnu analizu odabranih fenolnih jedinjenja primenjena LC-MS-MS tehnika. Spektrofotometrijskim metodama je određen sadržaj<br />ukupnih fenolnih komponenti i flavonoida. Ispitivanja biolo&scaron;kih aktivnosti ekstrakata obuhvatila su: određivanje antioksidantne i antiinflamatorne aktivnosti kao i sposobnost ekstrakata da inhibiraju acetilholinesterazu.&nbsp; Određen je uticaj odabranih metanolnih ekstrakata na imuni odgovor i proliferaciju intestinalnih ćelijskih linija pacova (IEC18) i ĉoveka (Caco2).<br />Dobijeni rezultati ukazuju da odabrane vrste tribusa Urticeae i Parietarieae, odnosno rodova&nbsp; Urtica&nbsp; i Parietaria&nbsp; predstavljaju bogate izvore biolo&scaron;ki aktivnih jedinjenja koja ispoljavaju raznovrsne biolo&scaron;ke aktivnosti. Sa hemotaksonomskog aspekta izdvajaju se sledeća jedinjenja kao potencijalni taksonomski markeri: vi&scaron;i sadržaj 5-O-kafeoilhinske kiseline u ekstraktima herbi vrsta roda&nbsp; Urtica, i visok sadrţaj<br />epikatehina u ekstraktima korena vrsta roda&nbsp; Parietaria. Ekstrakt herbe vrste&nbsp; U. kioviensis&nbsp; se od ostalih izdvaja po tome &scaron;to ne sadrži rutin a sadrži&nbsp; C-glikozide, u najvećoj meri viteksin. Od svih ispitivanih ekstrakata, ekstrakti korena&nbsp; Parietaria&nbsp; vrsta su ispoljili najbolji antioksidantni potencijal u većini izvr&scaron;enih testova. Najsnažniji antiinflamatorni potencijal je ispoljio ekstrakt korena vrste&nbsp; P. officinalis&nbsp; a prate ga ekstrakti korena vrsta roda&nbsp; Urtica.&nbsp; Veoma dobar antiinflamatorni potencijal su ispoljili infuzi herbi vrste U.<em> dioica</em>&nbsp; (čajevi od koprive). Svi ispitani metanolni ekstrakti su ispoljili odličnu inhibiciju enzima acetilholinesteraze a kao najbolji se izdvajaju ekstrakti korena&nbsp; Parietaria&nbsp; vrsta i vrste&nbsp; U.<em> kioviensis</em>. Povećanu sekreciju citokina rat MCP1 i GRO&alpha;&nbsp; izazivaju ekstrakti korena vrsta&nbsp; P. officinalis&nbsp; i&nbsp; P. judaica&nbsp; u<br />bazalnim uslovima i uslovima LPS-stimulisane inlamacije, dok ekstrakti vrste&nbsp; U. dioica&nbsp; povećavaju bazalnu a smanjuju LPS-stimulisanu sekreciju. Stimulaciju sekrecije ova dva citokina, ispitivani ekstrakti vr&scaron;e interakcijom sa adapternim proteinom MyD88 (ali ne intereaguju sa TLR4 receptorom) i NF -&kappa;B signalnim<br />putem. Ekstrakt korena vrste&nbsp; P. <em>officinalis</em>&nbsp; povećava LPS-om indukovanu ekspresiju enzima COX-2 u IEC18 ćelijama, dok je ekstrakt korena vrste&nbsp; U.<em> dioica</em>&nbsp; smanjuje. Efekat epitelizacije ili zarastanja rane na monosloju IEC18 ćelija ispoljavaju ekstrakti herbe i korena vrste&nbsp; P. <em>officinalis</em>. Ispitivani ekstrakti ne menjaju značajno seksreciju citokina hMCP1 i IL-8 u Caco2 ćelijama niti ispoljavaju značajan uticaj na &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; njihovu proliferaciju.</p> / <p>Within this doctoral thesis the chemical composition and biological activity of methanol and aqueous extracts of the selected plant species belonging to the Urticeae and Parietarieae tribe, more specifically to the&nbsp; Urtica&nbsp; and&nbsp; Parietaria&nbsp; genuses was evaluated (Urtica:&nbsp; U.<em> dioica</em>&nbsp; subsp.<em> dioica</em>&nbsp; var.&nbsp; <em>pubescens</em>,&nbsp; U.&nbsp; <em>dioica</em>&nbsp; subsp.&nbsp;<em> dioica</em>&nbsp; var.&nbsp; <em>dioica</em>&nbsp; and&nbsp; U.<em> kioviensis</em>;&nbsp; Parietaria:&nbsp; P<em>. officinalis</em>,&nbsp; P.<em> lusitanica</em>&nbsp; subsp.&nbsp; <em>lusitanica,</em>&nbsp; P. <em>judaica&nbsp;</em> subsp.<em>&nbsp; judaica&nbsp;</em> and<em>&nbsp; P. serbica</em>). The principal aim was to determine the content of biologically active&nbsp; compounds in this, poorly<br />examined species of the Urticaceae family, and determine their potential as additional remedy and dietary supplements.<br />Qualitative analysis of methanol extracts was performed by LC-DAD-MS i LC-MS/MS analysis, and LC-MS/MS for quantitative analysis of selected phenolic compounds. Total phenolics and flavonoids were determined spectrophotometrically. In order to assess the biological potential, the antioxidant and anti-inflammatory activities of the extracts were studied as well as&nbsp; their ability to inhibit acetylcholinesterase. The immuno-modulatory effects of the selected methanol extract on the immune response and proliferation of intestinal epithelial cells (IEC18 and Caco2)<br />was determined.<br />The obtained results suggest that the examined species of the Urticeae and Parietarieae tribe (genuses&nbsp; Urtica&nbsp; and&nbsp; Parietaria) are abundant with the biologically active compounds that express a broad spectrum of biological activities. As a potential chemotaxonomic markers stand out the following&nbsp; compounds: 5-O-caffeoilquinic acid (highly abundant in the herb extracts of the&nbsp; Urtica&nbsp; spp.) and epicatechin (highly abundant in the root extracts of the&nbsp; Parietaria&nbsp; spp.).&nbsp; U.<br />kioviensis&nbsp; herb extracts differs from the rest by high content of vitexin and total lack of rutin. The best antioxidant potential have exhibited the root extracts of the&nbsp; Parietaria&nbsp; species. The strongest anti-inflammatory potential had the root extract of the&nbsp; P. officinalis, followed by root extracts of the&nbsp; Urtica&nbsp; spp. Excellent anti-inflammatory activity have exhibited the aqueous&nbsp; extracts of&nbsp; U.<em> dioica</em>&nbsp; herbs&nbsp; &ndash;&nbsp; stinging nettle teas. All tested methanol extracts have inhibited enzyme acetylcholinesterase, the best inhibitors being root extracts of&nbsp; U.<em> kioviensis&nbsp;</em> and Parietaria&nbsp; species. Root extracts of&nbsp; P<em>. officinalis</em>&nbsp; and&nbsp; P.<em> judaica</em>&nbsp; have increased the basal and LPS-stimulated secretion of rat MCP1 and GRO&alpha;, while&nbsp; U. <em>dioica&nbsp;</em> extracts increased the basal but decreased the LPS-stimulated secretion. The examined extracts interact with the MyD88 (but not the TLR4) and NF-&kappa;B signaling pathway. The root extract of&nbsp; P<em>. officinalis&nbsp; </em>increase LPS-stimulated expression of COX-2 in IEC18 cells, while the root extract of&nbsp; U<em>. dioica</em>&nbsp; decreases it.<br />The herb and root extract of P. <em>officinalis</em>&nbsp; exhibit the wound healing effect. Investigated extracts do not significantly alter the secretion of hMCP1 and IL-8 in Caco2 cells and exhibit no significant effect to their proliferation.</p> / null

<p>&nbsp;&nbsp; Cilj ove doktorske disertacije predstavljalo je ispitivanje fitohemijskog sastava i biolo&scaron;ke aktivnosti vodenih i metanolnih ekstrakata svežih i suvih plodova, kao i voćne ka&scaron;e i džema pripremljenih po tradicionalnoj recepturi od plodova &scaron;est samoniklih vrsta <em>Rosa L.: R. canina, R. dumalis, R. dumetorum, R. tomentosa, R. arvensis, R. sempervirens. </em>Ispitivanje fitohemijskog sastava obuhvatalo je LC -MS/MS analizu 64 odabrana fenolna jedinjenja, hinske kiseline (organske kiseline) kao i tri triterpenoida. Takođe, izvr&scaron;eno je spektrofotometrijsko određivanje sadržaja ukupnih fenolnih i flavonoidnih jedinjenja, kao i vitamina C. Evaluacija biolo&scaron;ke aktivnosti obuhvatala je in vitro ispitivanja&nbsp; antioksidantne i antiinflamatorne aktivnosti, kao i ispitivanje uticaja ekstrakata odabranih vrsta Rosa na aktivnost enzima acetilholinesteraze i rast tumorskih i netumorskih ćelija.</p><p>&nbsp;&nbsp; Sumiranjem dobijenih rezultata može se zaključiti da sveži i suvi plodovi ispitivanih vrsta <em>Rosa</em>, kao i voćne ka&scaron;e i džemovi predstavljaju značajan izvor vitamina C i fenolnih jedinjenja, sa elagnom kiselinom kao najzastupljenijom fenolnom komponentom. Takođe u pojedinim ekstraktima vrsta<em> R. dumetorum</em> i<em> R. tomentosa</em> detektovana je visoka koncentracija ursolne kiseline, dok je hinska kiselina prisutna u značajnoj koncentraciji u svim ispitivanim ekstraktima.</p><p>&nbsp; &nbsp;Ekstrakti ispitivanih vrsta, izuzev vrste<em> Rosa arvensis</em>, pokazali su visok antioksidantni potencijal koji se ogleda u njihovoj sposobnosti neutralizacije nekoliko radikalskih vrsta, redukcionom potencijalu i sposobnosti inhibicije lipidne peroksidacije. Ispitivani ekstrakti ispoljili su umerenu antiinflamatornu aktivnost u pogledu inhibicije produkcije odabranih metabolita ciklooksigenaznog (12-HHT, TXB₂, PGE₂) i 12-lipooksigenaznog (12-HETE) metaboličkog puta arahidonske kiseline,&nbsp; posebno prostaglandina E&nbsp; . Takođe, in vitro ispitivanjem uticaja ekstrakata odabranih vrsta Rosa na aktivnost acetilholinesteraze pokazana je umerena aktivnost. Vodeni ekstrakti i ekstrakti voćnih ka&scaron;a vrsta <em>R. canina, R. tomentosa i R. sempervirens</em> pokazali su umereni inhibitorni potencijal prema rastu HeLa ćelijske linije, dok su ekstrakti vrste <em>R. sempervirens </em>pokazali aktivnost i prema HT-29 ćelijama. Dobijeni rezultati ukazuju na značajni potencijal plodova i tradicionalnih proizvoda ispitivanih vrsta <em>Rosa</em> za upotrebu u proizvodnji nutraceutika i funkcionalne hrane.</p> / <p>&nbsp;&nbsp; The aim of presented doctoral thesis was investigation of phytochemical composition and biological activity of water and methanol extracts of fresh and air-&nbsp; dried rose hips, as well as pur&eacute;e and jam made according to traditional recipe of&nbsp; hips of six wild growing<em> Rosa L. species: R. canina, R. dumalis, R. dumetorum, R</em>.&nbsp; <em>tomentosa, R. arvensis, and R. sempervirens.</em> Examination of phytochemical composition included LC-MS/MS analysis of 64 selected phenolic compounds, quinic&nbsp; acid (organic acid) and three triterpenoids. Also, total phenolic and flavonoid contents, as well as vitamin C contents were determined spectrophotometrically. Biological activity evaluation of extracts of six <em>Rosa</em> species included in vitro investigation of antioxidant, anti- inflammatory, anti-acetylcholinesterase and cytotoxic activity.<br />&nbsp;&nbsp; According to obtained results, fresh and air-dried rose hips, as well as their preserves present valuable source of vitamin C and phenolic compounds, especially&nbsp; ellagic acid, which was the most abundant examined phenolic compound. Furthermore, high concentration of ursolic acid was detected in some<em> Rosa &nbsp;</em> <em>tomentosa and R.&nbsp; rumetorum</em> extracts, while notable concentration of quinic acid&nbsp; was present in all examined extracts.<br />&nbsp;&nbsp; Extracts of all examined species, apart from <em>Rosa arvensis</em>, showed considerable antioxidant activity in terms of radical scavenging ability, reduction potential and inhibition of lipid peroxidation. Moreover, extracts exhibited moderate anti- inflammatory activity by means of inhibition of the main arachidonic acid metabolites &nbsp; formed incyclooxygenase-1 (12-HHT, TXB₂, PGE ₂ ) and 12-lipoxygenase (12-HETE)&nbsp; pathway, especially prostaglandin E₂ . Also, investigation of anti- cetylcholinesterase&nbsp; activity revealed moderate activity of extracts of all examined species. In addition,&nbsp; predominantly water extracts of fresh andair-dried rose hips, as well as pur&eacute;e of<em> R</em>.&nbsp; <em>canina, R. tomentosa </em>and <em>R. sempervirens</em> showed inhibitory activity toward HeLa, while <em>R.sempervirens</em> extracts also inhibited HT-29 cell growth. Presented results indicate significant potential of examined rose hips and their preserves for use as nutraceuticals and functional food.</p>

Les plantes médicinales constituent une source inexhaustible de composés (des produits naturels - PN) utilisé en médecine pour la prévention et le traitement de diverses maladies. L'introduction de nouvelles technologies et méthodes dans le domaine de la chimie des produits naturels a permis le développement de méthodes ‘high throughput’ pour la détermination de la composition chimique des extraits de plantes, l'évaluation de leurs propriétés et l'exploration de leur potentiel en tant que candidats médicaments. Dernièrement, la métabolomique, une approche intégrée incorporant les avantages des technologies d'analyse moderne et la puissance de la bioinformatique s’est révélé un outil efficace dans la biologie des systèmes. En particulier, l'application de la métabolomique pour la découverte de nouveaux composés bioactifs constitue un domaine émergent dans la chimie des produits naturels. Dans ce contexte, le genre Acronychia de la famille des Rutaceae a été choisi sur la base de son usage en médecine traditionnelle pour ses propriétés antimicrobienne, antipyrétique, antispasmodique et anti-inflammatoire. Nombre de méthodes chromatographiques modernes, spectrométriques et spectroscopiques sont utilisées pour l'exploration de leur contenu en métabolites suivant trois axes principaux constituant les trois chapitres de cette thèse. En bref, le premier chapitre décrit l’étude phytochimique d’Acronychia pedunculata, l’identification des métabolites secondaires contenus dans cette espèce et l'évaluation de leurs propriétés biologiques. Le deuxième chapitre vise au développement de méthodes analytiques pour l'identification des dimères d’acétophénones (marqueurs chimiotaxonomiques du genre) et aux stratégies utilisées pour la déréplication de ces différents extraits et la caractérisation chimique des composés par UHPLC-HRMSn. Le troisième chapitre se concentre sur l'application de méthodologies métabolomique (RMN et LC-MS) pour l'analyse comparative (entre les différentes espèces, origines, organes), pour des études chimiotaxonomiques (entre les espèces) et pour la corrélation des composés contenus avec une activité pharmacologique. / Medicinal plants constitute an unfailing source of compounds (natural products – NPs) utilised in medicine for the prevention and treatment of various deceases. The introduction of new technologies and methods in the field of natural products chemistry enabled the development of high throughput methodologies for the chemical composition determination of plant extracts, evaluation of their properties and the exploration of their potentials as drug candidates. Lately, metabolomics, an integrated approach incorporating the advantages of modern analytical technologies and the power of bioinformatics has been proven an efficient tool in systems biology. In particular, the application of metabolomics for the discovery of new bioactive compounds constitutes an emerging field in natural products chemistry. In this context, Acronychia genus of Rutaceae family was selected based on its well-known traditional use as antimicrobial, antipyretic, antispasmodic and anti-inflammatory therapeutic agent. Modern chromatographic, spectrometric and spectroscopic methods were utilised for the exploration of their metabolite content following three basic axes constituting the three chapters of this thesis. Briefly, the first chapter describes the phytochemical investigation of Acronychia pedunculata, the identification of secondary metabolites contained in this species and evaluation of their biological properties. The second chapter refers to the development of analytical methods for the identification of acetophenones (chemotaxonomic markers of the genus) and to the dereplication strategies for the chemical characterisation of extracts by UHPLC-HRMSn. The third chapter focuses on the application of metabolomic methodologies (LC-MS & NMR) for comparative analysis (between different species, origins, organs), chemotaxonomic studies (between species) and compound-activity correlations.