Triptolide(TP) from Tripterygium wilfordii has been demonstrated to possess anti-inflammatory, immunosuppressive, and anticancer activities. TP is specially used for the treatment of awkward rheumatoid arthritis, but ...Triptolide(TP) from Tripterygium wilfordii has been demonstrated to possess anti-inflammatory, immunosuppressive, and anticancer activities. TP is specially used for the treatment of awkward rheumatoid arthritis, but its clinical application is confined by intense side effects. It is reported that licorice can obviously reduce the toxicity of TP, but the detailed mechanisms involved have not been comprehensively investigated. The current study aimed to explore metabolomics characteristics of the toxic reaction induced by TP and the intervention effect of licorice water extraction(LWE) against such toxicity. Obtained urine samples from control, TP and TP + LWE treated rats were analyzed by UPLC/ESI-QTOF-MS. The metabolic profiles of the control and the TP group were well differentiated by the principal component analysis and orthogonal partial least squares-discriminant analysis. The toxicity of TP was demonstrated to be evolving along with the exposure time of TP. Eight potential biomarkers related to TP toxicity were successfully identified in urine samples. Furthermore, LWE treatment could attenuate the change in six of the eight identified biomarkers. Functional pathway analysis revealed that the alterations in these metabolites were associated with tryptophan, pantothenic acid, and porphyrin metabolism. Therefore, it was concluded that LWE demonstrated interventional effects on TP toxicity through regulation of tryptophan, pantothenic acid, and porphyrin metabolism pathways, which provided novel insights into the possible mechanisms of TP toxicity as well as the potential therapeutic effects of LWE against such toxicity.展开更多
目的对红花注射液进行化学成分分析及应用分子对接技术筛选红花注射液中过敏原成分。方法应用高效液相色谱-离子阱-飞行时间质谱高分辨质谱技术(high performance liquid chromatography-ion trap-time-of-flight high resolution mass ...目的对红花注射液进行化学成分分析及应用分子对接技术筛选红花注射液中过敏原成分。方法应用高效液相色谱-离子阱-飞行时间质谱高分辨质谱技术(high performance liquid chromatography-ion trap-time-of-flight high resolution mass spectrometry,HPLC-IT-TOF-MS)鉴定红花注射液中化学成分,应用分子对接技术进一步对潜在过敏原成分进行筛选。结果从红花注射液中共鉴定出40个化合物,其中26个查耳酮碳苷类化合物、8个黄酮类化合物、3个生物碱类化合物和3个其他类化合物,所有化合物均在负离子模式下鉴定。将这些化合物分别与人血清白蛋白(human serum albumin,HSA)、Mas相关G蛋白偶联受体X2(Mas-related G protein-coupled receptor X2,MRGPRX2)、Ras同源基因家族成员A(Ras homolog gene family member A)等蛋白进行分子对接,其中与HAS结合的化合物6个,与MRGPRX2结合的化合物有9个,发现红花注射液中过敏成分主要为6-羟基山柰酚类化合物和红花醌类化合物。结论建立了液-质联用与分子对接相结合的过敏原筛选方法,从红花注射液中鉴定出40个化合物,明确6-羟基山柰酚类和红花醌类化合物为潜在过敏原,为红花注射液过敏原筛选及其致敏机制研究提供了重要参考和数据。展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.81160541and 81373946)the Project of Health Department of Jiangxi Province(Grant No.2011A143)the priority academic program development of Jiangsu higher education institutions(PAPD)
文摘Triptolide(TP) from Tripterygium wilfordii has been demonstrated to possess anti-inflammatory, immunosuppressive, and anticancer activities. TP is specially used for the treatment of awkward rheumatoid arthritis, but its clinical application is confined by intense side effects. It is reported that licorice can obviously reduce the toxicity of TP, but the detailed mechanisms involved have not been comprehensively investigated. The current study aimed to explore metabolomics characteristics of the toxic reaction induced by TP and the intervention effect of licorice water extraction(LWE) against such toxicity. Obtained urine samples from control, TP and TP + LWE treated rats were analyzed by UPLC/ESI-QTOF-MS. The metabolic profiles of the control and the TP group were well differentiated by the principal component analysis and orthogonal partial least squares-discriminant analysis. The toxicity of TP was demonstrated to be evolving along with the exposure time of TP. Eight potential biomarkers related to TP toxicity were successfully identified in urine samples. Furthermore, LWE treatment could attenuate the change in six of the eight identified biomarkers. Functional pathway analysis revealed that the alterations in these metabolites were associated with tryptophan, pantothenic acid, and porphyrin metabolism. Therefore, it was concluded that LWE demonstrated interventional effects on TP toxicity through regulation of tryptophan, pantothenic acid, and porphyrin metabolism pathways, which provided novel insights into the possible mechanisms of TP toxicity as well as the potential therapeutic effects of LWE against such toxicity.
文摘目的对红花注射液进行化学成分分析及应用分子对接技术筛选红花注射液中过敏原成分。方法应用高效液相色谱-离子阱-飞行时间质谱高分辨质谱技术(high performance liquid chromatography-ion trap-time-of-flight high resolution mass spectrometry,HPLC-IT-TOF-MS)鉴定红花注射液中化学成分,应用分子对接技术进一步对潜在过敏原成分进行筛选。结果从红花注射液中共鉴定出40个化合物,其中26个查耳酮碳苷类化合物、8个黄酮类化合物、3个生物碱类化合物和3个其他类化合物,所有化合物均在负离子模式下鉴定。将这些化合物分别与人血清白蛋白(human serum albumin,HSA)、Mas相关G蛋白偶联受体X2(Mas-related G protein-coupled receptor X2,MRGPRX2)、Ras同源基因家族成员A(Ras homolog gene family member A)等蛋白进行分子对接,其中与HAS结合的化合物6个,与MRGPRX2结合的化合物有9个,发现红花注射液中过敏成分主要为6-羟基山柰酚类化合物和红花醌类化合物。结论建立了液-质联用与分子对接相结合的过敏原筛选方法,从红花注射液中鉴定出40个化合物,明确6-羟基山柰酚类和红花醌类化合物为潜在过敏原,为红花注射液过敏原筛选及其致敏机制研究提供了重要参考和数据。
