刺五加潜在靶点网络辅助活性成分效应的发现

Discovery of potential target network-aided active ingredient effect of Acanthopanax senticosus harms

目的:探讨刺五加醇提取物对机体的潜在保护作用和物质基础。方法:体外实验:首先采用UPLC-QTOF-MS对刺五加醇提取物的成分进行定性分析。其次,通过TCMSP数据库对每种成分进行成药性分析。再结合Pubmed数据库挖掘每种成分的生物学效应。最后结合前期代谢组学研究成果,构建刺五加的潜在作用靶点-药效物质网络。体内实验:SD雄性大鼠随机分为空白组和刺五加组(31.6 mg/kg),每组10只,每日灌胃一次,连续20天。测定大鼠肾脏组织一氧化氮(NO)含量。结果:发现了5种成药性良好的成分,分别为刺五加苷B、刺五加苷E、红景天苷、异类叶升麻苷和橄榄苦苷。与空白组相比(5.7±0.3)μmol/gprot,刺五加组可显著升高NO(12.7±1.3μmol/gprot)含量。通过潜在作用靶点-药效物质网络,发现橄榄苦苷可通过上调内源性代谢物四氢喋啶来增加NO在肾脏中的含量。结论:刺五加具有抗氧化和降低肾血管血压的作用的物质基础是橄榄苦苷,其机制可能与其上调内源性代谢物四氢喋啶的含量,激活瓜氨酸的表达,来增加NO在肾脏中的含量从而产生对肾脏血管的潜在保护作用有关。

Objective： To establish ethanol extract of AS potential protective targets and material basis network based on previous metabolomics research. Methods： Firstly,the components of ethanol extract of AS had been identified by UPLC-QTOF-MS. Secondly,the drug-likeness of every compound had been checked by TCMSP database. And then,biology effects of the compounds were acquired by Pubmed database after the drug-likeness being confirmed. At last,the potential protect targets and material basis network of ethanol extract of AS had been established based on previous metabolomic research. Results： We discovered syringin,eleutheroside E,salidroside,iso-acteoside and oleuropein.The five compounds had good drug-likeness. Ethanol extract of AS protected kidney vascular by increasing the content of NO by upregulating tetrahydropteridine in kidney. The NO content in kidney was upregulated by ethanol extract of AS which had been verified by spectrophotometry. The content of NO（5. 7 ± 0. 3） μmol/gprot-1 in the control group,after ethanol extract of AS treatment NO was upregulated to（12. 7 ±1. 3） μmol/gprot-1 with significant difference（P〈0. 05）. Conslusions： The oleuropein may be the material basis of the effect based on the potential protect targets and material basis network. Ethanol extract of AS could produce antioxidant and depress blood pressure of kidney vascular effect by upregulating NO content. The potential protect targets and material basis network is valuable for discovering the potential protect effects of traditional Chinese medicine.