Anticancer And Anti-inflammatory Activities Of A Standardized Dichloromethane Extract From Piper Umbellatum L. Leaves

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Despite the advances in anticancer drug discovery field, the worldwide cancer incidence is remarkable, highlighting the need for new therapies focusing on both cancer cell and its microenvironment. The tumor microenvironment offers multiple targets for cancer therapy, including inflammation. Nowadays, almost 75% of the anticancer agents used in chemotherapy are derived from natural products, and plants are an important source of new promising therapies. Continuing our research on Piper umbellatum species, here we describe the anticancer (in vitro antiproliferative activity and in vivo Ehrlich solid tumor model) and anti-inflammatory (carrageenan-induced paw edema and peritonitis models) activities of a standardized dichloromethane extract (SDE) from P. umbellatum leaves, containing 23.9% of 4-nerolidylcatechol. SDE showed in vitro and in vivo antiproliferative activity, reducing Ehrlich solid tumor growth by 38.7 and 52.2% when doses of 200 and 400 mg/kg, respectively, were administered daily by oral route. Daily treatments did not produce signals of toxicity. SDE also reduced paw edema and leukocyte migration on carrageenan-induced inflammation models, suggesting that the anticancer activity of SDE from Piper umbellatum leaves could involve antiproliferative and anti-inflammatory effects. These findings highlight P. umbellatum as a source of compounds against cancer and inflammation.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)CNPq [133897/2012-5

Anticancer and anti-inflammatory activities of a standardized dichloromethane extract from piper umbellatum l. leaves

Despite the advances in anticancer drug discovery field, the worldwide cancer incidence is remarkable, highlighting the need for new therapies focusing on both cancer cell and its microenvironment. The tumor microenvironment offers multiple targets for cancer therapy, including inflammation. Nowadays, almost 75% of the anticancer agents used in chemotherapy are derived from natural products, and plants are an important source of new promising therapies. Continuing our research on Piper umbellatum species, here we describe the anticancer (in vitro antiproliferative activity and in vivo Ehrlich solid tumor model) and anti-inflammatory (carrageenan-induced paw edema and peritonitis models) activities of a standardized dichloromethane extract (SDE) from P. umbellatum leaves, containing 23.9% of 4-nerolidylcatechol. SDE showed in vitro and in vivo antiproliferative activity, reducing Ehrlich solid tumor growth by 38.7 and 52.2% when doses of 200 and 400 mg/kg, respectively, were administered daily by oral route. Daily treatments did not produce signals of toxicity. SDE also reduced paw edema and leukocyte migration on carrageenan-induced inflammation models, suggesting that the anticancer activity of SDE from Piper umbellatum leaves could involve antiproliferative and anti-inflammatory effects. These findings highlight P. umbellatum as a source of compounds against cancer and inflammation2015CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES133897/2012-5sem informaçã

Pharmacological activity evoluation of microencapsulated and free crude dichloromethane extract from leaves of Piper umbellatum standardized in 4-nerolidylcatechol

Orientadores: Rodney Alexandre Ferreira Rodrigues, Mary Ann Foglio, João Ernesto de CarvalhoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de PiracicabaResumo: A espécie Piper umbellatum L., sinonímia Pothomorphe umbellata (L.) Miquel, é conhecida popularmente como pariparoba, caapeba e malvarisco. Tendo em vista as diferentes atividades biológicas comprovadas para a espécie Piper umbellatum e a técnica de microencapsulação por Spray Dryer, o objetivo desse trabalho foi avaliar a atividade farmacológica de extrato bruto padronizado (EBP) de P. umbellatum em modelos de câncer, inflamação, úlcera e verificar se as micropartículas de EBP apresentam atividade antiproliferativa in vitro. O extrato bruto diclorometânico de P. umbellatum possui 23,9% de 4-nerolidilcatecol aproximadamente. Foi avaliado a sua atividade anticâncer em modelo in vivo de tumor sólido de Ehrlich, atividade anti-inflamatória no edema da pata induzido por carragenina e peritonite. EBP foi capaz de reduzir o crescimento do tumor, quando administrado diariamente por via oral, sem sinais de toxicidade. Além disso, diminuiu o edema de pata e a migração de leucócitos no modelo de peritonite dessa forma, acredita-se existir uma relação entre a atividade anticâncer e anti-inflamatória. Também foi comprovada sua a atividade antiulcerogênica e gastroprotetora, relatada pelo uso popular no tratamento de úlceras gástricas. Os mecanismo de ação gastroprotetor envolvido na manutenção dos grupos sulfidrílicos, aumento de glutationa e de muco relacionam sua atividade antiulcerogênica à atividade antioxidante já descrita na literatura. O processo de microencapsulação por Spray Dryer do extrato bruto diclorometânico de P. umbellatum com o amido modificado Purity Gum 1773® permitiu alterar a propriedade graxa inerente a este extrato, insolúvel em água e foi capaz de manter sua atividade antiproliferativa in vitro. Dessa forma, a técnica de Spray Dryer pode ser um caminho para desenvolver um extrato seco de P. umbellatum. Portanto, podemos concluir que P. umbellatum pode ser fonte promissora para o desenvolvimento de novos agentes terapêuticos, tanto para o tratamento de úlceras gástricas quanto para inflamação e câncerAbstract: The species Piper umbellatum, is popularly known as "pariparoba", "caapeba" and "malvarisco". Despite the different biological activities certified for the species P. umbellatum and the technique of microencapsulation by Spray Dryer, the aim of this study was to evaluate the pharmacological activity of dichloromethane crude extract (DCE) from Piper umbellatum leaves in models of cancer, inflammation and gastric ulcer and also evaluate the antiproliferative activity of microparticles containing standardized crude extract (SDE) in a panel of human tumor cell lines. The SDE from P. umbellatum containing 23,9% of 4-nerolidylcatechol approximately and its in vivo anticancer activity in the Ehrlich solid tumor model as well as its anti-inflammatory activity on carrageenan induced paw edema and peritonitis. The SDE presented in vitro and in vivo antiproliferative activity, being capable to reduce tumor growth when administered daily by oral route, without signals of toxicity. It was also reduced paw edema induced and leukocyte migration on carrageenan induced peritonitis model. Thus establishing a relationship between the anticancer and anti-inflammatory activities.It was also confirmed the popular use of P. umbellatum in the treatment of gastric ulcers, as SDE presented gastroprotective action dependent of the sulfhydryl groups, increase glutatione and mucus pathway and possibly for its antioxidant potential. The microencapsulation process by Spray Dryer of SDE of P. umbellatum with modified starch (Purity Gum 1773®) allowed improvement of the extract solubility, without interfere on its in vitro antiproliferative activity. Thus, the technique of Spray Dryer may be a good alternative to the development of a dry extract of P. umbellatum. Therefore, we conclude that P. umbellatum is a promising source for the development of new therapeutic agents for the treatment gastric ulcers, inflammation and cancerMestradoFarmacologia, Anestesiologia e TerapeuticaMestra em Odontologi

Anticancer and Anti-Inflammatory Activities of a Standardized Dichloromethane Extract from Piper umbellatum L. Leaves

Despite the advances in anticancer drug discovery field, the worldwide cancer incidence is remarkable, highlighting the need for new therapies focusing on both cancer cell and its microenvironment. The tumor microenvironment offers multiple targets for cancer therapy, including inflammation. Nowadays, almost 75% of the anticancer agents used in chemotherapy are derived from natural products, and plants are an important source of new promising therapies. Continuing our research on Piper umbellatum species, here we describe the anticancer (in vitro antiproliferative activity and in vivo Ehrlich solid tumor model) and anti-inflammatory (carrageenan-induced paw edema and peritonitis models) activities of a standardized dichloromethane extract (SDE) from P. umbellatum leaves, containing 23.9% of 4-nerolidylcatechol. SDE showed in vitro and in vivo antiproliferative activity, reducing Ehrlich solid tumor growth by 38.7 and 52.2% when doses of 200 and 400 mg/kg, respectively, were administered daily by oral route. Daily treatments did not produce signals of toxicity. SDE also reduced paw edema and leukocyte migration on carrageenan-induced inflammation models, suggesting that the anticancer activity of SDE from Piper umbellatum leaves could involve antiproliferative and anti-inflammatory effects. These findings highlight P. umbellatum as a source of compounds against cancer and inflammation