Objective:Based on metabonomics technology of high-performance liquid chromatography-mass spectrometry(HPLC-MS/MS)and hydrogen nuclear magnetic resonance spectroscopy(^(1)H NMR),the pharmacokinetic characteristics and...Objective:Based on metabonomics technology of high-performance liquid chromatography-mass spectrometry(HPLC-MS/MS)and hydrogen nuclear magnetic resonance spectroscopy(^(1)H NMR),the pharmacokinetic characteristics and therapeutic mechanism of Rhei Radix et Rhizoma(RhRR,Dahuang in Chinese),Eupolyphaga Steleophaga(EuS,Tubiechong in Chinese)combined with RhRR acting on acute liver injury were explored.Methods:Models of acute liver injury were established,and the pharmacokinetic methods of five components of RhRR-EuS in rats were found by HPLC-MS/MS.The liver tissues of different groups of mice were analyzed by ^(1)H NMR spectroscopy combined with multivariate statistical analysis to investigate the metabolomics of RhRR-EuS and RhRR.Results:Pharmacokinetic results showed there were different levels of bimodal phenomenon in different groups,and the absorption of free anthraquinone in RhRR increased after compatibility with EuS.In addition,the pathological state of acute liver injury in rats can selectively promote the absorption of emodin,chrysophanol,physcion and aloe emodin.Through 15 differential metabolites in the liver tissue of acute liver injury mice,it was revealed that RhRR-EuS and RhRR could protect the liver injury by regulating the metabolism of glutamine and glutamic acid,alanine,aspartic acid and glutamic acid,and phosphoinositide.However,the regulation of RhRR was weaker than that of RhRR-EuS.Conclusion:For the first time,we studied the pharmacokinetics and metabolomics differences of RhRREuS and RhRR in rats and mice with acute liver injury,in order to provide theoretical reference for clinical treatment of liver disease by DHZCP.展开更多
目的探讨地鳖纤溶活性蛋白(fibrinolytic protein from Eupolyphaga sinensis Walker,EFP)对H22荷瘤小鼠的抑瘤功效。方法采用水提取法对地鳖进行成分分离;皮下接种肿瘤细胞建立荷瘤小鼠动物模型;灌胃和皮下注射法观察EFP的抑瘤作用;EL...目的探讨地鳖纤溶活性蛋白(fibrinolytic protein from Eupolyphaga sinensis Walker,EFP)对H22荷瘤小鼠的抑瘤功效。方法采用水提取法对地鳖进行成分分离;皮下接种肿瘤细胞建立荷瘤小鼠动物模型;灌胃和皮下注射法观察EFP的抑瘤作用;ELISA法检测血清抗H22抗体水平;记录各组体重变化、脾脏和胸腺等免疫器官的器官系数,检测肝脏丙二醛(MDA)水平、肝脏超氧化物歧化酶(SOD)活性、肝脏谷丙转氨酶(GPT)和谷草转氨酶(GOT)以及血清谷丙转氨酶(GPT)活力等生理生化指标。结果EFP具有明显的抑瘤活性。经EFP灌胃和皮下注射后的荷瘤小鼠,与对照组荷瘤小鼠相比其胸腺指数、脾指数明显增加;抗H22抗体水平以及MDA、SOD、GPT、GOT活性明显增加;肿瘤生长缓慢。结论EFP是地鳖抗肿瘤作用的主要有效成分,EFP在动物体内具有抗肿瘤作用,能通过增强荷瘤小鼠参与免疫抗体以及相关酶的活性而发挥抗肿瘤作用。展开更多
基金supported by the Key R&D Plan of Hubei Province for local special support in the field of general health(No.2022BCE066).
文摘Objective:Based on metabonomics technology of high-performance liquid chromatography-mass spectrometry(HPLC-MS/MS)and hydrogen nuclear magnetic resonance spectroscopy(^(1)H NMR),the pharmacokinetic characteristics and therapeutic mechanism of Rhei Radix et Rhizoma(RhRR,Dahuang in Chinese),Eupolyphaga Steleophaga(EuS,Tubiechong in Chinese)combined with RhRR acting on acute liver injury were explored.Methods:Models of acute liver injury were established,and the pharmacokinetic methods of five components of RhRR-EuS in rats were found by HPLC-MS/MS.The liver tissues of different groups of mice were analyzed by ^(1)H NMR spectroscopy combined with multivariate statistical analysis to investigate the metabolomics of RhRR-EuS and RhRR.Results:Pharmacokinetic results showed there were different levels of bimodal phenomenon in different groups,and the absorption of free anthraquinone in RhRR increased after compatibility with EuS.In addition,the pathological state of acute liver injury in rats can selectively promote the absorption of emodin,chrysophanol,physcion and aloe emodin.Through 15 differential metabolites in the liver tissue of acute liver injury mice,it was revealed that RhRR-EuS and RhRR could protect the liver injury by regulating the metabolism of glutamine and glutamic acid,alanine,aspartic acid and glutamic acid,and phosphoinositide.However,the regulation of RhRR was weaker than that of RhRR-EuS.Conclusion:For the first time,we studied the pharmacokinetics and metabolomics differences of RhRREuS and RhRR in rats and mice with acute liver injury,in order to provide theoretical reference for clinical treatment of liver disease by DHZCP.
文摘对土鳖虫水浸醇沉提取物2号样品进行了离子交换柱层析,得组分Ⅰ、Ⅱ、Ⅲ。实验结果表明,组分Ⅲ的溶栓活性明显高于组分Ⅰ和组分Ⅱ,其蛋白质含量为88.9%,分子量约为38,018,效价为313 UK/mg,比活力为352 UK/mg蛋白。将组分Ⅲ再进行凝胶过滤柱层析,得组分Ⅳ、Ⅴ、Ⅵ。组分Ⅵ的生物活性高于组分Ⅳ和组分Ⅴ,蛋白质含量为89.3%,电泳呈现两条带,分子量约为34,623和39,811,效价为77 UK/mg,比活力为86 UK/mg蛋白。将组分Ⅵ进行反相高效液相色谱柱层析,收集保留时间为17 m in的洗脱峰,得到土鳖虫纯蛋白质,呈白色絮状,极易溶于水。再一次用反相高效液相色谱检查其纯度,保留时间为17.073 m in,无杂质峰。纤溶活性实验结果表明,组分Ⅵ既有直接降解纤维蛋白的作用,同时也有纤溶酶原激活剂样作用。
文摘目的探讨地鳖纤溶活性蛋白(fibrinolytic protein from Eupolyphaga sinensis Walker,EFP)对H22荷瘤小鼠的抑瘤功效。方法采用水提取法对地鳖进行成分分离;皮下接种肿瘤细胞建立荷瘤小鼠动物模型;灌胃和皮下注射法观察EFP的抑瘤作用;ELISA法检测血清抗H22抗体水平;记录各组体重变化、脾脏和胸腺等免疫器官的器官系数,检测肝脏丙二醛(MDA)水平、肝脏超氧化物歧化酶(SOD)活性、肝脏谷丙转氨酶(GPT)和谷草转氨酶(GOT)以及血清谷丙转氨酶(GPT)活力等生理生化指标。结果EFP具有明显的抑瘤活性。经EFP灌胃和皮下注射后的荷瘤小鼠,与对照组荷瘤小鼠相比其胸腺指数、脾指数明显增加;抗H22抗体水平以及MDA、SOD、GPT、GOT活性明显增加;肿瘤生长缓慢。结论EFP是地鳖抗肿瘤作用的主要有效成分,EFP在动物体内具有抗肿瘤作用,能通过增强荷瘤小鼠参与免疫抗体以及相关酶的活性而发挥抗肿瘤作用。
