RESUMO
Carpesium macrocephalum (CM) Fr. et Sav. (Compositae) has been used in Chinese folk medicine as an analgesic, hemostatic, antipyretic, and to suppress inflammatory conditions. In the present study we aimed to provide scientific evidence for the anti-inflammatory properties of CM extract and evaluate the intrinsic mechanisms involved in both in vitro and in vivo experimental models. In in vitro findings, CM significantly inhibited the LPS-stimulated release of proinflammatory mediators such as nitric oxide, tumor necrosis factor-alpha, prostaglandin E2, and interleukin-6 in RAW264.7 macrophages in a concentration-dependent fashion. The attenuation of inflammatory responses in LPS-activated RAW264.7 cells by CM was closely associated with the suppression of nuclear factor-kappa B (NF-κB) phosphorylation, IκB-α degradation, and phosphorylation of Akt. CM treatment also attenuated the phosphorylation of STAT through TRIF dependent pathways in LPS-activated RAW264.7 cells. In vivo studies revealed that CM extract concentration dependently suppressed the acetic acid-induced vascular permeability in mice. Considering the data obtained regulation of multiple signaling mechanisms involving TRIF and Akt/NF-κB pathways might be responsible for the potent anti-inflammatory action of CM, substantiating its traditional use in inflammatory diseases.
Assuntos
Asteraceae , Permeabilidade Capilar/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Dinoprostona/imunologia , Endotoxinas/imunologia , Endotoxinas/toxicidade , Proteínas I-kappa B/efeitos dos fármacos , Proteínas I-kappa B/metabolismo , Interleucina-6/imunologia , Lipopolissacarídeos/imunologia , Lipopolissacarídeos/toxicidade , Macrófagos/imunologia , Camundongos , Inibidor de NF-kappaB alfa , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Óxido Nítrico , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Transcrição STAT/efeitos dos fármacos , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais/imunologia , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Triptolide is a compound isolated from the traditional Chinese medicinal herb Tripterygium wilfordii that shows potent anti-tumor activities, but its effects on acute myeloid leukemia with t(8;21) remain unclear. Here we report that triptolide inhibits cell proliferation and induces apoptosis in a dose- and time-dependent manner of t(8;21)-bearing Kasumi-1, SKNO-1 and CD34+ cells harvested from bone marrow samples of patients with t(8;21) leukemia. We show that triptolide triggers cleavage of the resultant AML1-ETO fusion protein of t(8;21), and causes downregulation of C-KIT followed by inhibition of JAK-STAT signaling. Triptolide downregulates p65 and inhibits the DNA-binding activity of NF-κB. Our data indicate that triptolide might be an effective agent for t(8;21) leukemia.