The effects of luteolin nanoparticles on the healing of extracted tooth socket in rabbits

Objective: To evaluate the effects of luteolin nanoparticles on the process tooth socket healing in rabbits. Design: This study comprised five rabbits randomly assigned to control animal and experimental animals. Immediately after the extraction of an upper maxillary incisor, the alveolar sockets of experimental animals were treated with topical luteolin while alveolar sockets of the control group remained without treatment. The animals were sacrificed by decapitation with deep anesthesia seven days post tooth extraction. The tooth sockets were sectioned and stained with hematoxylin and eosin stains. Results: Histological evaluation revealed that luteolin treatment induced earlier healing of extracted tooth sockets. Conclusion: These findings suggest that luteolin accelerates the healing process in tooth sockets of rabbits.

Adsorption/desorption characteristics and enrichment of quercetin, luteolin and apigenin from Flos populi using macroporous resin

Abstract In this study, the adsorption/desorption characteristics of quercetin, luteolin and apigenin from Flos populi extract (Populus tomentosa Carrière, Salicaceae) on twelve macroporous resins (NKA-9, HPD-600, HPD-826, HPD-750, HPD-400, DM-130, AB-8, SP-825, X-5, D-101, HPD-100, HPD-200) were evaluated. Both high adsorption and desorption capacities of quercetin, luteolin and apigenin from Flos populi extract on SP-825 resin indicated that SP-825 resin was appropriate and its data were well fitted to the Langmuir and Freundlich isotherms. To get the optimal separation process, the influences of factors such as flow rates, loading sample volumes, concentrations of desorption solution were further investigated. Column packed with SP-825 resin was used to perform dynamic adsorption and desorption experiments. After one round of treatment, the contents of quercetin, luteolin and apigenin in the final products were 3.75-fold, 3.67-fold and 3.54-fold increased with recovery yields of 87.25, 85.19 and 82.22%, respectively. The results showed that the preparative enrichment of quercetin, luteolin and apigenin was available via adsorption and desorption on SP-825 resin. This method is a promising basis for the large-scale preparation of quercetin, luteolin and apigenin from Flos populi.

Gastroprotective and antioxidant effects of Eremurus spectabilis Bieb. methanol extract and its isolated component isoorientin on indomethacin induced gastric ulcers in rats

Abstract Purpose: To investigate the gastroprotective effect of methanol extract of E. spectabilis and its major component isoorientin. Methods: Effects of isoorientin and methanol extract of E. spectabilis were investigated in indomethacin-induced gastric damage model on rats. Famotidine was used as the standard antiulcer drug. Numerical density of ulcer areas and oxidative status were determined on stomach tissues of rats. Results: All doses of isoorientin and methanol extract decreased MDA level and increased SOD activity and GSH levels in the stomach tissue of rats. When numerical density of ulcer areas were analized, the 500 mg/kg dose of methanol extract (84%) exhibited a similar effect to 20 mg/kg dose of standart drug famotidine (87%). Conclusions: The gastroprotective effects of E. spectabilis and its major constituent isoorientin in rats for the first time. Detailed analyses suggested that potential antioxidant activity of both plant extract and isoorientin mediates the gastroprotective effect.

Protective effect of luteolin on the transgenic Drosophila model of Parkinson's disease

In the present study we have studied the effect of 25, 50, 75 and 100 µM of luteolin on the transgenic Drosophila expressing human alpha synuclein. The doses of luteolin were established in diet and the PD flies were allowed to feed on it for 24 days. After 24 days of exposure the flies were assayed for climbing assay, oxidative stress markers, caspase-3 & 9 activity and dopamine content. The immunohistochemistry was also performed on the brain sections for the activity of tyrosine hydroxylase. The exposure of luteolin showed a dose dependent delay in the loss of climbing ability and activity, reduction in oxidative stress markers, caspase-3&9 activities and results in an increase in the dopamine content. The results obtained for the immunohistochemistry also supports the protective role of luteolin against the damage of the dopaminergic neurons

Reposicionamento de fármacos no câncer de boca: Identificação de possíveis agentes / Drug repositioning for oral cancer: Identifying candidate therapeutic agents

Objetivos: O objetivo deste estudo foi o de identificar compostos seletivamente tóxicos ao carcinoma espinocelular de boca in vitro por meio do reposicionamento de fármacos. Material e Métodos: Por meio de um escaneamento baseado na viabilidade celular de 1.280 fármacos, nós selecionamos três princípios ativos (luteolin, metixene hydrochloride e nitazoxanide) letais às células de câncer de boca SCC-25 e pouco tóxicos às células de queratinócitos cutâneos imortalizados HaCaT. Os fármacos candidatos foram investigados quanto à sua dose- e tempo-resposta bem como comparados e combinados à agentes quimioterápicos padrão por meio do ensaio por colorimetria com brometo de tiazolil azul de tetrazolio (MTT). O impacto dos fármacos na motilidade do SCC-25 e do HaCaT foi verificado pelo ensaio de migração celular e seus mecanismos de ação também foram explorados por meio da verificação dos níveis das proteínas fosforiladas pelo western blotting. Todos os experimentos foram realizados em triplicata e, pelo menos, três vezes independentes. O teste t de student foi utilizado para confrontar as variáveis e nível de significância de 5% foi estabelecido para todos os testes. Resultados: O flavonoide natural luteolin exerceu citotoxicidade potente contra as células de câncer de boca in vitro, apresentando baixa toxicidade ao HaCaT e alta eficiência quando comparado a quimioterápicos como a cisplatina e o AG1478. Do ponto de vista molecular, a luteolin ativou a via de sinalização do dano do DNA e, combinada com um inibidor do Chk, apresentou efeitos potencializados. Além disso, nós demonstramos que a nitazoxanide e o metixene hydrochloride são capazes de destruir células SCC-25 porém não as HaCaT de maneira proporcional à dose e ao tempo de tratamento. As combinações entre os três fármacos hit e com a cisplatina ou o AG1478 potencializaram seus efeitos contra as células malignas. Conclusões: O presente estudo traz a luteolin, o metixene hydrochloride e a nitazoxanide como...

Objectives: Here we aimed at identifying and reposition approved drugs that could be selectively toxic towards oral squamous cell carcinoma cells. Materials and Methods: Through a cell-based drug screening of 1,280 chemical molecules, we selected 3 compounds (luteolin, metixene hydrochloride, and nitazoxanide) lethal to oral cancer SCC-25 cells, while sparing immortalized keratinocyte HaCaT cells. The drugs were then further challenged for their time- and dose-responses, as well as their comparison and combination to standard chemotherapeutic agents by colorimetric assay 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan, Thiazolyl blue formazan (MTT). The impact on SCC-25 and HaCaT motility as well as the mode of action of the drugs was then further explored by scratching assay and western blotting, respectively. All the experiments were performed in triplicated and, at least, three independent times. Students t test was performed to verify the differences among the variables and the level of significance was set at 5%. Results: The natural flavonoid luteolin was a potent cytotoxic agent against oral cancer cells in vitro, presenting low toxicity against HaCaT cells and high efficiency as compared to standard-of-care, such as cisplatin and AG1478. From a molecular standpoint, luteolin coopted the DNA-damage pathway and could be efficiently combined with Chk pharmacological inhibitor. Moreover, we demonstrated that nitazoxanide and metixene hydrochloride kill the SCC-25 but not the HaCaT cells in a dose- and time-dependent. The combinations among the three drugs hit and with cisplatin and AG1478 improved their effect against the malignant cells. Conclusions: Luteolin, metixene hydrochloride, and nitazoxanide emerge as strong cytotoxic and/or adjuvant therapy in oral cancer, as these compounds present higher efficiency and lower toxicity against oral cancer cells in vitro than conventional chemotherapeutic agents.

Reposicionamento de fármacos no câncer de boca: Identificação de possíveis agentes / Drug repositioning for oral cancer: Identifying candidate therapeutic agents

O objetivo deste estudo foi o de identificar compostos seletivamente tóxicos ao carcinoma espinocelular de boca in vitro por meio do reposicionamento de fármacos. Material e Métodos: Por meio de um escaneamento baseado na viabilidade celular de 1.280 fármacos, nós selecionamos três princípios ativos (luteolin, metixene hydrochloride e nitazoxanide) letais às células de câncer de boca SCC-25 e pouco tóxicos às células de queratinócitos cutâneos imortalizados HaCaT. Os fármacos candidatos foram investigados quanto à sua dose- e tempo-resposta bem como comparados e combinados à agentes quimioterápicos padrão por meio do ensaio por colorimetria com brometo de tiazolil azul de tetrazolio (MTT). O impacto dos fármacos na motilidade do SCC-25 e do HaCaT foi verificado pelo ensaio de migração celular e seus mecanismos de ação também foram explorados por meio da verificação dos níveis das proteínas fosforiladas pelo western blotting. Todos os experimentos foram realizados em triplicata e, pelo menos, três vezes independentes. O teste t de student foi utilizado para confrontar as variáveis e nível de significância de 5% foi estabelecido para todos os testes. Resultados: O flavonoide natural luteolin exerceu citotoxicidade potente contra as células de câncer de boca in vitro, apresentando baixa toxicidade ao HaCaT e alta eficiência quando comparado a quimioterápicos como a cisplatina e o AG1478. Do ponto de vista molecular, a luteolin ativou a via de sinalização do dano do DNA e, combinada com um inibidor do Chk, apresentou efeitos potencializados. Além disso, nós demonstramos que a nitazoxanide e o metixene hydrochloride são capazes de destruir células SCC-25 porém não as HaCaT de maneira proporcional à dose e ao tempo de tratamento. As combinações entre os três fármacos hit e com a cisplatina ou o AG1478 potencializaram seus efeitos contra as células malignas. Conclusões: O presente estudo traz a luteolin, o metixene hydrochloride e a nitazoxanide como...

Here we aimed at identifying and reposition approved drugs that could be selectively toxic towards oral squamous cell carcinoma cells. Materials and Methods: Through a cell-based drug screening of 1,280 chemical molecules, we selected 3 compounds (luteolin, metixene hydrochloride, and nitazoxanide) lethal to oral cancer SCC-25 cells, while sparing immortalized keratinocyte HaCaT cells. The drugs were then further challenged for their time- and dose-responses, as well as their comparison and combination to standard chemotherapeutic agents by colorimetric assay 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan, Thiazolyl blue formazan (MTT). The impact on SCC-25 and HaCaT motility as well as the mode of action of the drugs was then further explored by scratching assay and western blotting, respectively. All the experiments were performed in triplicated and, at least, three independent times. Students t test was performed to verify the differences among the variables and the level of significance was set at 5%. Results: The natural flavonoid luteolin was a potent cytotoxic agent against oral cancer cells in vitro, presenting low toxicity against HaCaT cells and high efficiency as compared to standard-of-care, such as cisplatin and AG1478. From a molecular standpoint, luteolin coopted the DNA-damage pathway and could be efficiently combined with Chk pharmacological inhibitor. Moreover, we demonstrated that nitazoxanide and metixene hydrochloride kill the SCC-25 but not the HaCaT cells in a dose- and time-dependent. The combinations among the three drugs hit and with cisplatin and AG1478 improved their effect against the malignant cells. Conclusions: Luteolin, metixene hydrochloride, and nitazoxanide emerge as strong cytotoxic and/or adjuvant therapy in oral cancer, as these compounds present higher efficiency and lower toxicity against oral cancer cells in vitro than conventional chemotherapeutic agents...

Efeito de flavonóides e de corantes do urucum sobre a hiperlipidemia induzida em coelhos / Flavonoids and natural urucum dyes on induced hyperlipidemic rabbits

Induziu-se hipercolesterolemia em coelhos da raça Nova Zelândia e comparam-se os efeitos hipolipidêmicos, por via oral, dos flavonóides baicaleína, morina, naringenina, naringina, quercetina, rutina, crisina, luteolina e apigenina, os corantes naturais extraidos do urucum norbixina e bixina e o medicamento comercial hipolipidêmico colestiramina. Todos os flavonóides estudados e o corante bixina foram significativamente mais hipocolesterolêmicos que o medicamento colestiramina, sendo que as melhores reduções foram observadas com naringenina (54,04%), naringina (49,26%), quercetina (49,78%), rutina (48,89%), crisina (55,56%), luteolina (52,58%) e apigenina (49,88%). As substâncias que mais aumentaram o HDL foram os flavonóides baicaleína (122,21%), apigenina (281,63%), morina (10,79%) e luteolina (21,14%) e o medicamento colestiramina (37,26%). A maior parte dos falvonóides estudados reduziu mais o tricilglicerol do que o medicamento colestiramina, sendo a baicaleína (-56,91% do que o controle sadio) e a rutina os mais eficientes. Verificou-se também in vitro, que a bixina, norbixina, apigenina e luteolina aumentaram a atividade da lipase. Tais resultados indicam que os compostos estudados poderiam ser utilizados como medicamento se devidamente testados no homem. Os cortes histológicos do arco aórtico e da artéria aorta não mostraram diferenças entre os grupos tratados e os controles, enquanto que algumas diferenças histológicas foram observadas nos hepatócitos dos grupos tratados em relação aos coelhos hiperlipidêmicos.