RESUMO
Melicope ptelefolia has been traditionally used to treat rheumatism and fever. The present study aimed to investigate the therapeutic effect of 3,5diCßDglucopyranosyl phloroacetophenone (ßGP), a main component of M. ptelefolia, on rheumatoid arthritis (RA). A model of collageninduced arthritis (CIA) was established in mice using the RAW 264.7 murine macrophage cell line and mouse embryonic fibroblasts (MEFs). The clinical scores of arthritis, swelling, histopathological findings, and microcomputed tomography in CIA mouse paws were assessed. The levels of antitype II collagen antibody and cytokines were determined in the plasma and cell culture supernatant, respectively. Protein and gene expression levels were analyzed by western blot and reverse transcriptionquantitative polymerase chain reaction analyses. ßGP significantly decreased the gross arthritic scores of CIA mice and joint swelling, and decreased articular inflammation, cartilage degradation and bone erosion. However, ßGP did not exert any effect on antitype II collagen immunoglobulin G plasma levels or inflammatory cytokine expression in macrophages. ßGP significantly suppressed the expression of interleukin6 and leukemia inhibitory factor and decreased the phosphorylation of signal transducer and activator of transcription 3, and expression of receptor activator of nuclear factorκB ligand in tumor necrosis factorαstimulated MEFs and in CIA mouse paws. Osteoclastrelated gene expression was significantly reduced in CIA mouse paws. Taken together, ßGP suppressed the development of RA by regulating the activation of synovial fibroblasts.
Assuntos
Acetofenonas/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Fibroblastos/efeitos dos fármacos , Glucosídeos/uso terapêutico , Acetofenonas/química , Animais , Anti-Inflamatórios/química , Artrite Experimental/patologia , Artrite Reumatoide/patologia , Citocinas/análise , Fibroblastos/patologia , Glucosídeos/química , Masculino , Camundongos , Osteoclastos/efeitos dos fármacos , Osteoclastos/patologia , Células RAW 264.7 , Rutaceae/química , Microtomografia por Raio-XRESUMO
Accumulative evidence suggests ginseng extract and/or its major components, ginsenosides and compound K, a metabolized ginseng saponin, have anti-cancer effects. In the present study, the effects of a ginseng butanolic extract (GBX) and an enzymatically fortified ginseng extract (FGX), with enriched ginsenosides and compound K, on the growth of KATO3 human gastric cancer cells were investigated using a cell viability assay. While treatment with GBX at 31.25-125 mg/ml for 24 h did not affect the proliferation of KATO3 cells, FGX under the same conditions inhibited cell proliferation in a concentration-dependent manner. Furthermore, Annexin V/PI-staining and flow cytometric analysis demonstrated that the population of apoptotic KATO3 cells was increased following treatment with FGX, which was greater than in the GBX-treated cells, suggesting that FGX had a stronger apoptotic effect than GBX. To investigate the underlying mechanism of the cytostatic and cytotoxic effects of the ginseng extracts, apoptosis-associated proteins were assessed using western blot analysis. The data revealed higher expression levels of B-cell lymphoma 2-associated X protein (Bax), lower expression of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor α (IκBα) and reduced phosphorylation of mammalian target of rapamycin (mTOR) and protein kinase B (PKB) in the FGX-treated KATO3 cells than in the GBX-treated cells. Collectively, these results demonstrated for the first time, to the best of our knowledge, that FGX had stronger anti-proliferative and pro-apoptotic effects on KATO3 cells than GBX. The anti-proliferative and/or pro-apoptotic effects of FGX appeared to be mediated via the upregulation of Bax, IκBα proteolysis (activation of nuclear factor-κB) and the blocking of mTOR and PKB signals.
Assuntos
Apoptose/efeitos dos fármacos , Proteínas I-kappa B/metabolismo , Panax/química , Exsudatos de Plantas/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Gástricas/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteína X Associada a bcl-2/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo , Ginsenosídeos/química , Ginsenosídeos/farmacologia , Humanos , Inibidor de NF-kappaB alfa , FosforilaçãoRESUMO
Molecular inflammation is a pivotal process in various degenerative immune diseases, including asthma and atopic dermatitis. In this study, we examined the effects of Helianthus annuus seed (HAS) aqueous extract on an in vivo anti-asthmatic model. Ovalbumin-induced mice were orally administered the aqueous extract of Helianthus annuus seeds, and their lungs were assessed by hematoxylin and eosin staining. Moreover, the expression levels of IL-4/IL-13 cytokines and IgE were determined. HAS extract induced a decrease in CD4+ cell number, IL-4/IL-13 expression, and IgE secretion levels in the lungs. Our findings collectively suggest that the HAS extract has considerable potential in reducing the asthma-like symptoms induced by a mouse ovalbumin challenge model. However, further isolation and purification of the extract is required to determine the specific factor(s) responsible for its anti-asthmatic activity.