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胀果甘草中的Nrf2激活剂及其对小鼠四氯化碳诱导肝损伤的肝保护活性。

Nrf2 activators from Glycyrrhiza inflata and their hepatoprotective activities against CCl-induced liver injury in mice.

作者信息

Lin Yan, Kuang Yi, Li Kai, Wang Shuang, Ji Shuai, Chen Kuan, Song Wei, Qiao Xue, Ye Min

机构信息

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, People's Republic of China.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, People's Republic of China.

出版信息

Bioorg Med Chem. 2017 Oct 15;25(20):5522-5530. doi: 10.1016/j.bmc.2017.08.018. Epub 2017 Aug 15.

Abstract

Glycyrrhiza inflata (licorice) has been used to treat liver diseases for a long history. However, the bioactive compounds are still not clear. In this work, 77 compounds, including 9 new ones, were isolated from the EtOAc extract of the roots and rhizomes of G. inflata. The Nrf2 activation activities of all compounds were screened using ARE-luciferase reporter assay on HepG2C8 cells. The results indicated a number of chalcones were potent Nrf2 activators, including 11 (licochalcone A, 4.07-fold), 12 (licochalcone B, 5.17-fold), and 19 (echinatin, 4.09-fold). Further studies indicated that 11, 12 and 19 remarkably attenuated CCl-induced acute liver injury in mice (10 or 50mg/kg, 7days, ig.). These compounds could be promising hepatoprotective natural agents.

摘要

胀果甘草(甘草)用于治疗肝脏疾病已有很长历史。然而,其生物活性化合物仍不明确。在本研究中,从胀果甘草根和根茎的乙酸乙酯提取物中分离出77种化合物,其中包括9种新化合物。使用ARE-荧光素酶报告基因检测法在HepG2C8细胞上筛选了所有化合物的Nrf2激活活性。结果表明,一些查耳酮是有效的Nrf2激活剂,包括化合物11(甘草查耳酮A,激活倍数为4.07倍)、12(甘草查耳酮B,激活倍数为5.17倍)和19(刺芒柄花素,激活倍数为4.09倍)。进一步研究表明,化合物11、12和19显著减轻了CCl4诱导的小鼠急性肝损伤(10或50mg/kg,7天,灌胃)。这些化合物可能是有前景的保肝天然药物。

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