RESUMEN
FR429 is an ellagitannin with a potential antitumor activity, isolated and purified from Polygonum capitatum Buch.-Ham.ex D.Don, which is a traditional Miao-nationality herbal medicine in Guizhou and Yunnan of China. Our preliminary result of pharmacology study has indicated that the antitumor activity of FR429. However, the metabolism of FR429 has not been reported yet. In this study, LC-ion trap-time of flight mass spectrometry (LC-IT-TOF/MS) was used to characterize unpredictable metabolites of FR429 biotransformed by intestinal bacteria in vitro. Total thirteen metabolites were detected and characterized via comparisons of their accurate molecular masses and fragment ions of each MS(n) stage with those of the parent drug, and four of them were also elucidated by NMR. The results demonstrated that FR429 could be transformed by intestinal bacteria in vitro, mainly via hydrolysis and reduction reaction. This work provided a basis for the further study on the biotansformation of FR429 in vivo.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacocinética , Bacterias/metabolismo , Cromatografía Liquida/métodos , Glucósidos/química , Glucósidos/farmacocinética , Taninos Hidrolizables/química , Taninos Hidrolizables/farmacocinética , Mucosa Intestinal/metabolismo , Intestinos/microbiología , Animales , Biotransformación , Medicina de Hierbas , Hidrólisis , Espectroscopía de Resonancia Magnética/métodos , Medicina Tradicional China , Ratas , Ratas Sprague-DawleyRESUMEN
Chemoresistance has imposed a great challenge for cancer therapy. Fructus Ligustri Lucidi (FLL) is one of the commonest Chinese herbs that has been used for thousand years. This study shows that the aqueous extract of FLL (AFLL) enhanced the sensitivity of DLD-1 colon cancer cells to doxorubicin-induced apoptosis. Furthermore, Tbx3 expression was found to be suppressed by AFLL when the expression of tumor suppressor genes p14 and p53 were activated. Therefore, reduction of Tbx3 rescued the dysregulated P14(ARF)-P53 signaling, which in turn contributed to the sensitivity of DLD-1 cells to doxorubicin-induced apoptosis. As a conclusion, the findings suggest that FLL has a potential of being an appealing agent for auxiliary chemotherapy in treatment of human colorectal carcinoma.
Asunto(s)
Apoptosis/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Doxorrubicina/farmacología , Ligustrum/química , Extractos Vegetales/farmacología , Proteínas de Dominio T Box/antagonistas & inhibidores , Antibióticos Antineoplásicos/farmacología , Procesos de Crecimiento Celular/efectos de los fármacos , Línea Celular Tumoral , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Sinergismo Farmacológico , Humanos , Extractos Vegetales/química , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/genética , Proteínas de Dominio T Box/biosíntesis , Proteínas de Dominio T Box/genética , Transfección , Proteína p14ARF Supresora de Tumor/genética , Proteína p14ARF Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Herba Epimedii is one of the most commonly used Chinese herbs for treating osteoporosis. In the present study, the flavonoids of Herba Epimedii (HEF) have shown to promote the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. They were noted to enhance the mRNA expression of BMP-2, BMP-4, Runx2, beta-catenin and cyclinD1, all of which are BMP or Wnt-signaling pathway related regulators. The osteogenic effect was inhibited by the introduction of noggin and DKK-1, which is classical inhibitor of BMP and Wnt/beta-catenin signaling, respectively. These results suggest that HEF exerts promoting effect on osteogenic differentiation, which plausibly functions via the BMP and Wnt/beta-catenin signaling pathways. Considering the therapeutic efficiency and economical issues, HEF may be a potential candidate for promoting bone regeneration. On the other hand, osteogenic differentiation of MSCs may also be a promising and attractive tool to apply in bone repair.