A new series of derivatives N-acihidrazone (NAH) pirazinic was rationally planned be applied the strategy of simplification molecular on the unit quinoxalinic of prototype LASSBio-1018, identified as a potent anti-inflammatory and analgesic in LASSBio® designed by application the biososterism of rings on LASSBio-319. The new series of 21 derivatives were synthesized and subjected to experiments to determine the antinociceptive and anti-inflammatory activity. Were used mice of swiss line, of both sexes (20 to 35 g) and rats Wistar of both sexes (100-220 g). The substances were administered by p.o. (100 &#956;mol/kg), except morphine which was administered pathway i.p. (15 &#956;mol/kg). The indomethacin, celecoxib, thalidomide and morphine were used as standart drugs. For evaluation antinociceptive were performed the constriction abdominal assay, hyperalgesia induced-formalin and hot plate test. The anti-inflammatory action were investigated by the assay capsaicin-induced ear edema, peritonitis zymosan A-induced and assay of induction of syndrome arthritis experimental. On the constriction abdominal assay all compounds inhibited the constriction significantly standing out the prototypes LASSBio-1181 e LASSBio-1188 (97% and 86%) (p < 0,01), respectively. On the formalin assay the LASSBio-1186 was able to significantly modulate the antinociceptive response in the neurogenic phase (average latency of 12 s). In first phase thirteen prototypes inhibited the inflammatory response and the LASSBio-1181 LASSBio-1256 and the most active time. On the Capsaicin-induced ear edema of six prototypes showed statistically significant inhibition, highlighting the LASSBio- 1181 (69%) and LASSBio-1182 (63%) among the most active. On the assay of zymosan Ainduced peritonitis of the LASSBio-1180 inhibition of 56.95% of the response. On the assay of arthritis the LASSBio-1181 and thalidomide were capable reduce of swelling in the paw several days of treatment. On the hot plate test of any of the prototypes was active. Considering these data we can conclude that the prototypes were able to modulate the antinociceptive response in both models of nociception (formalin and constriction abdominal), demonstrating a great potential antinociceptive and that may not involve core components, is seen, all the derivatives present no inhibition in hot plate test. The second phase of the formalin model were identified several prototypes with anti-inflammatory action that can be confirmed by testing of ear edema. These results infer that the prototypes are capable of modulating the response peripheral antinociceptive and anti-inflammatory. / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Uma nova série de derivados N-acilidrazônicos (NAH) pirazínicos foi racionalmente planejada aplicando-se a estratégia de simplificação molecular sobre a unidade quinoxalínica do protótipo LASSBio-1018, identificado como potente antiinflamatório e analgésico no LASSBio® desenhado por aplicação do bioisosterismo de anéis sobre o protótipo LASSBio-319. A nova série de 21 derivados foi sintetizada e submetida a experiências para determinação de atividade antinociceptiva e antiinflamatória. Foram utilizados camundongos da linhagem Swiss, de ambos os sexos (20 a 35 g) e ratos Wistar de ambos os sexos (100-220 g). As substâncias foram administradas por v.o (100 &#956;mol/kg), com exceção da morfina que foi administrada por via i.p. (15 &#956;mol/kg). O celecoxib, indometacina, morfina e talidomida foram utilizados como padrões de referência. Para avaliação antinociceptiva foram realizados os ensaios de contorção abdominal induzida por ácido acético, nocicepção induzida por formalina e modelo de placa quente. A ação antiinflamatória foi investigada pelo método de edema de orelha induzido por capsaicina, pelo ensaio de peritonite induzida por Zymosan A e pelo método de indução da síndrome de artrite experimental. No ensaio de contorção abdominal, todos os compostos inibiram as contorções de forma significativa, destacando-se os protótipos LASSBio-1181 e LASSBio-1188 com inibição de 97% e 86% (p < 0,001), respectivamente. No ensaio de formalina o LASSBio- 1186 foi capaz de modular significativamente a resposta antinociceptiva na fase neurogênica (80,79%). Na fase inflamatória treze protótipos inibiram a resposta sendo o LASSBio-1181 (86,05%) e LASSBio-1256 (86,50%) os mais ativos. No ensaio de edema de orelha seis protótipos apresentaram inibição estatisticamente significativa, destacando-se o LASSBio- 1181 (69%) e LASSBio-1182 (63%) entre os mais ativos. No ensaio de peritonite o LASSBio-1180 induziu inibição de 56,95% da resposta. No ensaio de indução de artrite o LASSBio-1181 e a talidomida foram capazes de diminuir o edema da pata em vários dias do tratamento. No ensaio de placa quente nenhum dos protótipos foi ativo. Diante destes dados pode-se concluir que os protótipos foram capazes de modular a resposta antinociceptiva nos dois modelos de nocicepção (contorção e formalina), demonstrando um grande potencial antinociceptivo e que possivelmente não envolve componentes centrais, haja vista, todos os derivados não apresentaram inibição no ensaio de placa quente. A segunda fase do modelo de formalina permitiu identificar vários protótipos com ação antiinflamatória, que pode ser confirmada pelo ensaio de edema de orelha. Esses resultados permitem inferir que os protótipos são capazes de modular a resposta antinociceptiva periférica e resposta antiinflamatória.

Submitted by Irene Nascimento (irene.kessia@ufpe.br) on 2016-11-24T14:57:09Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Chrisjacele Tese CCB Bioquimica e Fisiologia.pdf: 1964201 bytes, checksum: 106af1b3d737e6027907a88876429988 (MD5) / Made available in DSpace on 2016-11-24T14:57:09Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Chrisjacele Tese CCB Bioquimica e Fisiologia.pdf: 1964201 bytes, checksum: 106af1b3d737e6027907a88876429988 (MD5) Previous issue date: 2015-02-23 / Facepe / As plantas do gênero Bauhinia (Família Fabaceae) são encontradas na África, Ásia bem como América Central e do Sul. No Brasil, elas são conhecidas como “pata-de-vaca“ e as suas folhas são usadas popularmente em forma de chá (infusão) para o tratamento de diabetes, como anti-inflamatório e como analgésico. Dentre diversos compostos purificados de plantas estão as lectinas, as quais são proteínas ou glicoproteínas que se ligam a carboidratos, por reconhecimento específico e reversível. Das folhas da espécie Bauhinia monandra foi purificada uma lectina galactose específica (BmoLL, B. monandra Leaf Lectin) através de cromatografia de afinidade em gel de guar. Diante das atividades descritas para as lectinas e do uso das plantas do gênero Bauhinia na medicina popular, foi levantada a hipótese de que as atividades biológicas relatadas pela população B. monandra têm como princípio ativo a lectina BmoLL. Desta forma o objetivo do presente estudo foi investigar propriedades toxicológicas, hipoglicemiante, anti-inflamatória e antinociceptiva da lectina. BmoLL não apresentou toxicidade para camundongos, uma vez que não induziu a morte nem perda de peso a 2000 mg/kg. Além disso, ela não afetou a sobrevivência de Artemia salina nas concentrações testadas (250-1.000 μg/mL). A atividade hipoglicemiante da BmoLL foi avaliada utilizando em camundongos NOD (non obese diabetic) como modelo experimental. Camundongos NOD diabéticos foram tratados com BmoLL (60 mg/kg/dia) por administração intraperitoneal durante 21 dias. O efeito da lectina foi comparado com os dados obtidos para um grupo diabético não-tratado e e um grupo não-diabético (normoglicêmico). No final do experimento, os animais tratados com BmoLL exibiram uma redução do nível de glicose no sangue (de 307,5 ± 83,3 mg/dL para 137,5 ± 68,3 mg/dL), atingindo valores semelhantes ao do grupo normoglicêmico (110,5 ± 16,7 mg/dL). O grupo diabético não-tratado apresentou concentração de glicose sanguínea ≥500 mg/dL. Além disso, as concentrações de triglicéridos e VLDL-colesterol no sangue foram significativamente reduzidas (p<0,05) pelo tratamento com BmoLL, em comparação com os animais diabéticos não tratados. Para avaliação da atividade antiinflamtória, foi realizado primeiramente o método de edema de pata induzido por carragenina. BmoLL reduziu a inflamação significativamente (p<0,05) em 47% (30 mg/kg) e 60,5% (60mg/kg). O grupo controle, tratado com ácido acetilsalicílico, apresentou 70,5% de redução. Na avaliação da atividade atiinflamatória por ensaio de peritonite, a migração de leucócitos foi significativamente reduzida (p<0,05) no grupo tratado com BmoLL, sendo o resultado semelhante ao obtido com grupo tratado com ácido acetilsalicílico. Na avaliação da atividade antinociceptiva BmoLL, os tratamentos com doses de 15, 30 e 60 mg/kg reduziram significativamente (p<0,05) o número de contorções abdominais (induzidas por ácido acético) em 43,1%, 50,1% e 71,3%, respectivamente. No ensaio de placa quente, a BmoLL em doses de 30 e 60 mg/kg, mostrou um efeito antinociceptivo significativo (p<0,05). Em conclusão, BmoLL é uma molécula interessante para ser estudada mais profundamente quanto a suas aplicações farmacológicas, desde que não apresentou toxicidade aguda para camundongos e demonstrou as atividades hipoglicemiante, anti-inflamatória e antinociceptiva, não apresentou toxicidade para A. salina nem para camundongos. / Plants of Bauhinia genus are found in Africa, Asia as well as in Central and South America. In Brazil, they are know as “pata-de-vaca” and their leaves are popularly used as tea (infusion) to treat diabetes, as anti-inflamatory and as analgesic. Among the compounds isolated from plants, there are the lectins, which Consist in protein or glycoproteins that bind carbohydrates by reversible and specific recognizement. From the leaves of Bauhinia monandra, it was isolated a galactose-specific lectin (BmoLL, B. monandra Leaf Lectin) by affinity chromatography on guar gel. In face of the biological activities described for lectins and the use of Bauhinia plants in folk medicine, it was hypothesized whether the biological activities reported by population for B. monandra have the lectin BmoLL as active principle. In this sense, the aim of this work was to investigate toxicological, hypoglycemic, anti-inflammatory, and antinociceptive properties of the lectin. BmoLL did not show toxicity to mice since it did not induce death and weight loss at 2,000 mg/kg. In addition, it did not affect the survival of Artemia salina at the tested concentrations (250-1,000 μg/mL). The hypoglicemic activity of BmoLL was evaluated using NOD (non obese diabetic) mice as experimental model. Diabetic NOD mice were treated with BmoLL (60 mg/kg/day) by intraperitoneal administration during 21 days. The lectin effect was compared with data obtained for a non-treated diabetic group and a non-diabetic (normoglycemic) group. At the end of the experiment, animals treated with BmoLL showed reduction in blood glucose level (dfrom 307.5 ± 83.3 mg/dL to 137.5 ± 68.3 mg/dL), reaching values similar to those from normoglycemic group (110.5 ± 16.7 mg/dL). Non-treated diabetic group showe blood glucose ≥500 mg/dL. In addition, the concentrations of triglycerides and VLDL-cholesterol in blood were also significantly (p<0.05) reduced by the treatment with BmnoLL, in comparison with non-treated diabetic animals. For the evaluation of the anti-inflammatory activity, it was first performed the carragenan-induced paw edema method. BmoLL reduced the inflammation significantly (p<0.05) in 47% (30 mg/kg) and 60.5% (60 mg/kg). The control group, treated with acetylsalycilic acid, showed a 70.5% reduction. In the evaluation of anti-inflammatory activity by peritonitis model, the leukocyte migration was significantly (p<0.05) reduced in the group treated with BmoLL, being the result similar to that obtained for the group trated with acetylsalycilic acid. In the evaluation of the antinociceptive activity of BmoLL, the treatments with doses of 15, 30, and 60 mg/kg reduced significantly (p<0.05) the number of abdominal writhings (induced by acetic acid) in 43.1%, 50.1% and 73.1%, respectively. In hot plate assay, BmoLL at 30 and 60 mg/kg showed a significant antinociceptive effect. In conclusion, BmoLL is an interesting molecule to be more deeply studied for its pharmacological applications since it did not show acute toxicity to mice and showed the biological activities described in this work.

<p>Karakterizacija metanolnih ekstrakata jedanaest vrsta samoniklih bokvica (rod<em> Plantago L.</em>) obuhvatala je fitohemijski skrining i ispitivanje antioksidantne i antiinflamatorne aktivnosti. Primenom LC-MS/MS tehnike odreĊen je sadržaj odabranih sekundarnih biomolekula. Antioksidantna aktivnosti ekstrakata (sposobnost neutralizacije slobodnih radikala, redukcioni potencijal i inhibicija lipidne peroksidacije) ispitana je primenom spektrofotometrijskih metoda. U cilju odreĊivanja antiinflamatornog potencijala, razvijena je<em> in vitro </em>metoda za praćenje aktivnosti trombocitne ciklooksigenaze-1 i 12-lipoksigenaze. Svi ispitani ekstrakti pokazali su znaĉajnu biolo&scaron;ku aktivnost.</p> / <p>Characterization of methanol extracts of eleven<em> Plantago L.</em> species included phytochemical screening and evaluation of antioxidant and anti-inflammatory activity. The content of several secondary metabolites was determined by LC-MS/MS technique. Antioxidant activity of extracts (radical scavenger capacity, reduction potential and inhibition of lipid peroxidation) was examined by spectrophotometric methods. With the intention to evaluate anti-inflammatory activity, an<em> in vitro method</em> was developed to measure activity of platelet cyclooxygenase-1 and 12-lipoxygenase. All examined extracts showed noticeable biological activity.</p>

Ximenia americana L. (Oleacaceae) is a plant used in folk medicine in several countries for the treatment of inflammation and pain. This work describes the antinocipeptive, anti-inflammatory and antioxidant activities of the ethanolic extract, fractions (aqueous, acetate, hexane and chloroform) and an epicatechin (XACC-I) isolated from the stem bark of X. americana L. The activity antinociceptive was tested in several models: acetic acid-induced writhing, formalin test and hot plate test. In the writhing test of the extract, fractions and XACC-1 were able to induce inhibition of the number of constrictions in: ethanol extract (98.2 %), aqueous fraction (95.5 %), hexane fraction (92.3 %), chloroform fraction (99.5 %), acetate fraction (95.0%), and XACC-I (98.5%). Still utilizing this model the dose-response curve of XACC-I with a dose of 1-300 &#956;mol/Kg was calculated, which showed an DI50 = 38.3 &#956;mol/Kg, CL 95 %: 10.7 - 117.8 &#956;mol/Kg and standard drug dipyrone showed an DI50 = 29.3 &#956;mol/kg, CL 95 %: 22.7 - 75.4 &#956;mol/Kg. In the formalin test the ethanolic extract of the aqueous fraction in the second phase of the experiment resulted in an inhibition time of paw licking in 82.4 and 73.7 % respectively, the chloroform fraction was able to induce inhibition of only early phase of the experiment by 31.5 % to XACCI inhibited the nociceptive response in neurogenic and inflammatory phase respectively in 64.2 % and 86.8 %. The ethanol extract, all fractions and XACC-I have not been active in hot plate test, which aims to evaluate the central antinociceptive activity. The anti-inflammatory action was investigated by test of peritonitis induced by zymosan A and carrageenan. In the test of the peritonitis induced by zymosan A, the ethanolic extract, acetate and aqueous fractions, the XACC-I and the standard drug indomethacin induced inhibition of cell recruitment by 41.4 %, 38.6 %, 35.1 %, 46.0 % and 55.7 % respectively. Using the carrageenan, the ethanolic extract, fractions (acetate, aqueous, chloroform and hexane), the XACC-I and the standard drug indomethacin induced inhibition of cell recruitment in 63.5 %, 55.9 %, 69,2 %, 35.8 %, 62.1 %, 66.1 % and 72.0 % respectively. Only the ethanol extract and hexane fraction did not induce the death of any animal, the acute toxicity of XACC-I have not been evaluated. In the test of DPPH (2,2-diphenyl-1-picrylhydrazyl) the ethanolic extract, all fractions and XACC-1 showed high antioxidant activity. The ethanolic extract, acetate and aqueous fractions showed high concentration of total phenols observed using the spectrophotometric assay with Folin-Ciocalteu. These results infer that the ethanol extract, fractions and XACC-I from the stem bark of X. americana are able to modulate the antinociceptive peripheral and acute inflammatory response. / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Ximenia americana L. (Oleacaceae) é uma planta utilizada na medicina popular em diversos países para o tratamento de inflamação e dor. Este trabalho versa sobre o estudo da atividade antinocipetiva, antiinflamatória e antioxidante do extrato etanólico, frações (aquosa, acetato, hexano e clorofórmica) e de uma epicatequina (XACC-I) isolada da casca do caule de X. americana L. Para avaliar a antinocicepção (na dose de 100 mg/Kg i.p., para o extrato e frações e de 100 &#956;mol/Kg i.p. para a XACC-I) foram utilizados os ensaios: contorções abdominais induzidas por ácido acético em camundongos; nocicepção induzida por formalina; ensaio de placa quente. No ensaio de contorções abdominais o extrato, frações e XACC-1 foram capazes de induzir a inibição do número de contorções em: extrato etanólico (98,2 %), fração aquosa (95,5 %), fração hexano (92,3 %), fração clorofórmica (99,5 %), fração em acetato (95,0 %), e a XACC-I (98,5 %). Neste mesmo modelo realizou-se a curva doseresposta da XACC-I com a dose de 1 300 &#956;mol/Kg que induziu uma DE50= 38,3 &#956;mol/Kg, limite de confiança 95 %: 10,7 117,8 &#956;mol /Kg e o fármaco padrão dipirona induziu uma DE50 = 29,3 &#956;mol /Kg, limite de confiança 95 %: 22,7 75,4 &#956;mol/Kg. No ensaio de nocicepção induzida por formalina o extrato etanólico e a fração aquosa na segunda fase do experimento, induziram uma inibição do tempo de lambida de pata em 82,4 e 73,7 % respectivamente, a fração clorofórmio foi capaz de induzir a inibição apenas da primeira fase do experimento em 31,5 % a XACC-I inibiu a resposta nociceptiva na fase neurogênica e inflamatória respectivamente em 64,2 % e 86,8 %. O extrato etanólico bem como todas as frações e a XACC-I não foram ativos no ensaio de placa quente, que visa à avaliação da atividade antinociceptiva central. A ação anti-inflamatória foi investigada pelo ensaio de peritonite induzida por Zymosan A e Carragenina utilizando a dose de 100 mg/Kg i.p., para o extrato e frações e de 100 &#956;mol/Kg para a XACC-I. No ensaio de peritonite induzida por Zymosan A o extrato etanólico, frações acetato e aquosa, a XACC-I e o fármaco padrão indometacina induziram a inibição do recrutamento celular em 41,4 %, 38,6 %, 35,1 %, 46,0 % e 55,7 % respectivamente. Utilizando-se outro agente flogístico (carragenina) o extrato etanólico, frações (acetato, aquosa, clorofórmica e hexano), a XACC-I e o fármaco padrão indometacina induziram a inibição do recrutamento celular em 63,5 %, 55,9 %, 69,2 %, 35,8 %, 62,1 %, 66,1 % e 72,0 % respectivamente. Apenas o extrato etanólico e a fração hexano não induziram a morte de nenhum animal, a toxicidade aguda da XACC-I não foi avaliada pela pouca quantidade da substância. No teste de atividade sequestrante de radicais in vitro pelo método do DPPH (2,2-difenil-1-picrilhidrazila) o extrato etanólico, todas as frações e XACC-1 apresentaram alta atividade sequestrante radicalar. O extrato etanólico, frações aquosa e acetato apresentaram alto teor de fenóis totais observado utilizando-se o ensaio espectrofotométrico com o reagente Folin-Ciocalteu. Diante destes dados pode-se concluir que o extrato etanólico, frações e a XACC-I provenientes da casca do caule da X. americana L. são capazes de modular a resposta antinociceptiva periférica e anti-inflamatória aguda.

<p>Karakterizacija metanolnih ekstrakata i etarskih ulja iglica i &scaron;i&scaron;arki osam vrsta samoniklih kleka (rod Juniperus L.) obuhvatala je fitohemijski skrining i ispitivanje antioksidantne, antiinflamatorne i antimikrobne aktivnosti. Primenom LC-MS/MS i GC-MS tehnike detektovan i odreĎen je sadržaj fenolnih i terpenoidnih sekundarnih biomolekula. Antioksidantna aktivnost ekstrakata i etarskih ulja (sposobnost neutralizacije slobodnih radikala, redukcioni potencijal i inhibicija lipidne peroksidacije) ispitana je primenom spektrofotometrijskih metoda. U cilju odreĎivanja antiinflamatornog potencijala, primenjena je ex vivo metoda za praćenje aktivnosti trombocitne ciklooksigenaze-1 i 12-lipoksigenaze. Antimikrobna aktivnost etarskih ulja odreĎena je na &scaron;est odabranih bakterijskih sojeva. Ispitani ekstrakti i etarska ulja pokazali su značajnu biolo&scaron;ku aktivnost.</p> / <p> Characterization of methanol extracts and essential oils of eight Juniperus L. species included phytochemical screening and evaluation of antioxidant, anti-inflammatory and antimicrobial activity. The presence and content of phenolics and terpenoids was confirmed by LC-MS/MS and GC-MS technique. Antioxidant activity of extracts and essential oils (radical scavenger capacity, reduction potential and inhibition of lipid peroxidation) was examined by spectrophotometric methods. With the intention to evaluate anti-inflammatory activity, an ex vivo method was applied to measure activity of platelet cyclooxygenase-1 and 12-lipoxygenase. Antimicrobial activity was evaluated according to six bacterial strains. Examined extracts and essential oils showed noticeable biological activity.</p>

<p>Ispitani su hemijski sastav i biolo&scaron;ka aktivnost &scaron;est samoniklih vrsta iz tribusa Scandiceae<br />(familija Apiaceae): Anthriscus sylvestris, Anthriscus cerefolium, Chaerophyllum bulbosum,<br />Chaerophyllum hirsutum, Chaerophyllum temulentum i Scandix pecten-veneris. LC-MS-MS<br />analizom ekstrakata identifikovano je vi&scaron;e desetina sekundarnih biomolekula iz klasa flavonoida,<br />fenilpropenskih kiselina, lignana i kumarina. GC-MS analiza pružila je uvid u sastav volatilnih<br />komponenti i njihov hemosistematski značaj. Potvrđeno je da sve ispitivane vrste imaju umereno<br />antioksidantno, antiinflamatorno i antiproliferativno dejstvo.</p> / <p> Chemical composition and biological activity of six wild-growing species from<br /> Scandiceae tribe (Apiaceae family) &ndash; Anthriscus sylvestris, Anthriscus cerefolium, Chaerophyllum<br /> bulbosum, Chaerophyllum hirsutum, Chaerophyllum temulentum and Scandix pecten-veneris &ndash; was<br /> examined. By LC-MS-MS analysis, a large number of secondary biomolecules was identified in<br /> extracts, including flavonoids, phenylpropenic acids, lignans and coumarins. GC-MS analysis<br /> provided insight into volatile components composition and chemosystematic significance. All<br /> investigated species exhibited moderate antioxidant, anti-inflammatory and antiproliferative<br /> activity.</p>

<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>