RESUMO
As cancer markers, hydrogen peroxide (H2 O2 ) and viscosity play an essential role in the development of tumors. Meanwhile, based on the performance of near-infrared (NIR) fluorescence imaging and the high efficiency of photodynamic therapy (PDT) and photothermal therapy (PTT) synergistic therapy, it is urgent to develop a dual-key (H2 O2 and viscosity) activated fluorescence probe for cancer phototherapy. Herein, a NIR-I/II fluorescence probe named BX-B is reported. In the presence of both H2 O2 and viscosity, the fluorescence signal of NIR-I (810 nm) and NIR-II (945 nm) can be released. In the presence of H2 O2 , the PDT and PTT effects are observed. BX-B is used to monitor its therapeutic effects in cancer cells and tumor-bearing mice due to the increased viscosity caused by PDT and PTT. In addition, the tumors of mice treated with BX-B are almost completely ablated after the laser irradiation based on its PDT and PTT synergistic therapy. This work provides a reliable platform for effective cancer treatment and immediate evaluation of therapeutic effects.
Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Animais , Camundongos , Terapia Fototérmica , Fluorescência , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Fototerapia , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/farmacologiaRESUMO
A method based on ultra-high performance liquid chromatography with triple quadrupole/linear ion trap mass spectrometry(UHPLC-QTRAP-MS/MS) was developed for the simultaneous determination of 33 active constituents, including flavonoids, organic acids, nucleosides, and amino acids in Taxilli Herba to analyze and evaluate the dynamic accumulation of their multiple active constituents. The separation was performed at 30 â on an XBridge~® C_(18) column(4.6 mm×100 mm, 3.5 µm) with gradient elution using 0.1% formic acid aqueous solution-methanol as the mobile phase at a flow rate of 0.5 mL·min~(-1), and the injection volume was 2 µL. The constituents were ionized in the electrospray ionization source(ESI) and quantitated by the multiple reaction monitoring(MRM) mode. The entropy weight TOPSIS method was used to objectively assign weights to the target constituents and rank them according to their relative closeness coefficient(C_i) to construct a multi-index comprehensive evaluation model of Taxilli Herba. The results showed that the concentrations and peak areas of 33 target constituents had good linearity in their respective linear ranges, and the correlation coefficients(r) were not less than 0.999 0. The RSD of precision, reproducibility, and stability were not higher than 4.7%. The average recoveries were 98.03%-101.3% with RSD less than 4.0%. There were differences in the content of 33 active constituents in Taxilli Herba at different harvest periods. The overall quality of Taxilli Herba harvested from mid-February to early March was better, which was consistent with the traditional harvest period. This study provides basic information for revealing the rule of dynamic accumulation of multiple active constituents in Taxilli Herba and determining the suitable harvesting period. Meanwhile, it also provides a new methodological reference for the comprehensive evaluation of the intrinsic quality of Taxilli Herba.
Assuntos
Flavonoides , Espectrometria de Massas em Tandem , China , Cromatografia Líquida de Alta Pressão/métodos , Flavonoides/química , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodosRESUMO
To explore the color value changes after processing and further explore the correlations between color values and internal components, we established a rapid evaluation method for the quality of Glycyrrhizae Radix et Rhizoma and Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle. In this study, the color values of Glycyrrhizae Radix et Rhizoma and Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle were digitized by a spectrophotometer, and the standard ranges of color values of the two herbal medicines were established. Further, a discriminant analysis model was established to quickly and accurately distinguish the two herbal medicines. The content of 9 flavonoids and 1 triterpene in Glycyrrhizae Radix et Rhizoma and Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle were determined by HPLC, and Pearson correlation analysis was adopted to analyze the correlations between the color values and the content of 10 components. The standard ranges of L~*, a~*, and b~* values were 65.539 6-68.305 8, 7.296 3-8.467 3, and 29.998 8-32.212 8 for Glycyrrhizae Radix et Rhizoma, and 43.654 3-47.166 4, 14.050 0-15.133 8, and 16.424 6-20.984 8 for Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle, respectively. Glycyrrhizae Radix et Rhizoma had higher L~* and b~* values and lower a~* value than Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle, which indicated that processing with honey decreased the white and yellow values and increased the red value. The original and cross validation of the established discriminant analysis model met the requirements, and the external validation of the model showed the prediction accuracy of 100%. Pearson correlation analysis showed that the a~* value was positively correlated with the content of liquiritin apioside and isoliquiritin apioside(P<0.05), while the L~* and b~* values were negatively correlated with the content of the above two components(P<0.05). After processing with honey, L~* and b~* decreased while a~* increased, and the content of liquiritin apioside and isoliquiritin apioside increased, which was consistent with the content determination results. This study reveals the regularity of the color values of Glycyrrhizae Radix et Rhizoma after processing with honey roasting, as well as the correlations between color values and component content, which provides a basis for the rapid quality evaluation of Glycyrrhizae Radix et Rhizoma and Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle.
Assuntos
Medicamentos de Ervas Chinesas , Glycyrrhiza , Plantas Medicinais , Medicamentos de Ervas Chinesas/análise , Rizoma/químicaRESUMO
Taxilli Herba (TAXH) is an important traditional Chinese medicine with a long history, dating from the Eastern Han Dynasty to the present times. However, the active constituents in it that parasitize different hosts vary, affecting its clinical efficacy. Given the complexity of the host origins, evaluating the quality of TAXH is critical to ensure the safety and effectiveness of clinical medication. In the present study, a quantitative method based on ultra-fast liquid chromatography tandem triple quadrupole mass spectrometry (UFLC-QTRAP-MS/MS) was established, which simultaneously determined the content of 33 active constituents, including 12 flavonoids, 4 organic acids, 12 amino acids, and 5 nucleosides in 45 samples. Orthogonal partial least squares discriminant analysis (OPLS-DA) was employed to classify and distinguish between TAXH and its adulterants, Tolypanthi Herba (TOLH). A hierarchical clustering analysis (HCA) was conducted combined with a heatmap to visually observe the distribution regularity of 33 constituents in each sample. Furthermore, gray relational analysis (GRA) was applied to evaluate the quality of samples to get the optimal host. The results demonstrated that TAXH excelled TOLH in quality as a whole. The quality of TAXH parasitizing Morus alba was also better, while those that were parasitic on Cinnamomum camphora and Glyptostrobus pensilis had relatively poor quality. This study may provide comprehensive information that is necessary for quality control and supply a scientific basis for further exploring the quality formation mechanism of TAXH.
Assuntos
Medicamentos de Ervas Chinesas/análise , Aminoácidos/análise , Cromatografia Líquida de Alta Pressão , Flavonoides/análise , Medicina Tradicional Chinesa , Análise Multivariada , Nucleosídeos/análise , Controle de Qualidade , Espectrometria de Massas em TandemRESUMO
The reduced coenzymes (NADH and NADPH) are an important product in energy metabolism and closely related to the occurrence and development of cancer. So it is necessary to use a powerful detection tool to visualize NAD(P)H in energy metabolism of tumor cells and find a new strategy to improve cancer treatment based on NAD(P)H. Herein, a novel multifunctional probe (Cy-N) is synthesized with good near-infrared fluorescence (NIRF) response to NAD(P)H and the photoacoustic (PA) and photothermal properties are successfully activated by NAD(P)H. The probe is successfully applied in visualizing NAD(P)H in energy metabolism of tumor cells and imaging NAD(P)H in bacteria. Moreover, the probe can be used to image NAD(P)H in energy metabolism of tumor-bearing mice by dual-modal imaging (NIRF and PA). More importantly, in terms of the role of NAD(P)H in energy metabolism, the photothermal therapy (PTT) is activated by NAD(P)H and a novel strategy of enhanced PTT is proposed by injecting glucose. As far as we know, this is the first probe to detect NAD(P)H in energy metabolism through dual-modal imaging, and also the first probe to activate PTT based on NAD(P)H, which will provide important information of the diagnosis and treatment of cancer.
Assuntos
Nanopartículas , Neoplasias , Técnicas Fotoacústicas , Terapia Fototérmica , Animais , Linhagem Celular Tumoral , Metabolismo Energético , Camundongos , NADP , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Fototerapia , Nanomedicina TeranósticaRESUMO
Sophoridine, a natural product obtained from medicinal plants, which has a variety of pharmacological effects, including anti-cancer effects, and selectively induces apoptotic cell death in a variety of human cancer cells in vitro and in vivo; however, its mechanism of action needs to be further elaborated. In this study, we investigated the effects of Sophoridine on the induction of apoptosis in human Glioma U87MG cells. Here, we found that Sophoridine can significantly inhibited cell proliferation, G2/M phase arrest, induced cell apoptosis and caused reactive oxygen species (ROS) generation and GSH content reduction. Sophoridine also triggered significant down-regulated the expression of p27, CDK2, Survivin, Livin, Bcl-2, E2F1 and the transcriptional activity of FoxM1, NF-κb and AP-1, meanwhile, up-regulated the expression of caspase-3/8, p53, Smac, c-JNK and p38-MAPK. Moreover, we found that Sophoridine significantly inhibited ubiquitin-proteasome in tumor cells. In conclusion, Sophoridine shows obvious anti-cancer activity on glioma cells by inducing cell apoptosis, inducing ROS accumulation, and activating mitochondrial signal pathways. Eventually, we believe Sophoridine could be used as a new drug for the treatment of glioma.