Estudo do efeito in vitro e in vivo da apigenina em Leishmania amazonensis / Study of the in vitro and in vivo effect of apigenin in leishmania amazonensis

A leishmaniose ainda é uma das doenças mais negligenciadas do mundo. Ela está presente nos cinco continentes e é endêmica em 98 países, com 350 milhões de pessoas vivendo em zonas de risco e mais de 12 milhões de pessoas infectadas. Compreende um complexo de doenças causadas por mais de 20 espécies do gênero Leishmania. No Brasil, a Leishmania amazonensis é uma espécie dermotrópica importante. Apesar do progresso na compreensão da bioquímica e biologia deste parasito, este conhecimento ainda não tem refletido na descoberta de novos e eficazes agentes quimioterápicos contra a doença. O tratamento atual é insatisfatório, com altas taxas de toxidez e ineficácia, e não há vacina humana licenciada. A pesquisa de novos medicamentos, a partir de fontes naturais, é amplamente utilizada como uma abordagem bem sucedida na detecção de compostos para o tratamento de doenças parasitárias. Compostos puros obtidos de plantas, como certos flavonoides, exibem atividade antiprotozoária. A apigenina é uma flavona bioativa, abundantemente presente em frutas,ervas e legumes, que mostrou atividade leishmanicida. A apigenina inibiu o crescimento celular de ambas as formas evolutivas de L. amazonensis de maneira dose-dependente. Este efeito inibitório, em promastigotas, foi igual a 74 por cento após 24 h de tratamento com 96 miM de apigenina e, em amastigotas intracelulares, foi igual a 71 por cento após 72 h de tratamento com 12miM do composto. O IC50/24 h em promastigotas foi 23,68 M e o IC50/72 h em amastigotas foi 4,33 miM. Observou-se que a apigenina foi capaz de induzir o aumento nos níveis de EROnos promastigotas e nos macrófagos infectados com L. amazonensis...

Leishmaniasis is still one of the most neglected diseases in the world. It is present on fivecontinents and is endemic in 98 countries, with 350 million people living in areas at risk andmore than 12 million people infected. Comprises a complex of diseases caused by over 20species of the genus Leishmania. In Brazil, Leishmania amazonensis is an importantdermotropic specie. Despite progress in understanding the biochemistry and biology of thisparasite, this knowledge has not been reflected in the discovery of new and effectivechemotherapeutic agents against the disease. The current treatment is unsatisfactory, withhigh toxicity and ineffectiveness, and there is no licensed human vaccine. The research ofnew drugs from natural sources is widely used as a successful approach in detectingcompounds for the treatment of parasitic diseases. Pure compounds obtained from plants,such as certain flavonoids, exhibit antiprotozoal activity. Apigenin is a bioactive flavone,abundantly present in fruits, herbs and vegetables, which showed leishmanicidal activity.Apigenin inhibited cell growth of both forms of L. amazonensis in dose-dependent manner.This inhibitory effect on promastigotes was equal to 74 percent after 24 h of treatment with 96miMapigenin and on intracellular amastigotes was equal to 71 percent after 72 h of treatment with 12 miM of the compound. The IC50/24 h) in promastigotes was 23.68 miM and the IC50/72 h inamastigotes was 4.33 miM. It was observed that apigenin was able to induce increased levels ofROS in treated promastigotes and L. amazonensis-infected macrophages...

Effects of Scutellarin on MUC5AC Mucin Production Induced by Human Neutrophil Elastase or Interleukin 13 on Airway Epithelial Cells

Scutellarin is a flavonoid extracted from a traditional Chinese herb, Erigeron breviscapus. The present study investigated the effect of scutellarin on MUC5AC mucin production and the possible mechanism. Human bronchial epithelial 16 (HBE16) cells were pretreated with scutellarin for 60 min, and then exposed to human neutrophil elastase (HNE) or interleukin (IL)-13 for 12 hr. RT-PCR and ELISA were performed to measure the amount of MUC5AC mucin production. The results showed that scutellarin inhibited MUC5AC expression both in mRNA and protein level induced by HNE in a concentration-dependent manner. However, scutellarin failed to inhibit MUC5AC mucin production induced by IL-13. To investigate the intracellular mechanisms associated with the effect of scutellarin on MUC5AC mucin production, western blotting was carried out to examine the phosphorylation of protein kinase C (PKC), signal transducer and activator of transcription 6 (STAT6) and extracellular signal-regulated kinase 1/2 (ERK1/2). The phosphorylation of PKC and ERK1/2 was attenuated after treatment with scutellarin, whereas STAT6 was not significantly affected. Therefore, it is suggested that scutellarin down-regulates MUC5AC mucin production on HBE16 cells via ERK-dependent and PKC-dependent pathways.