Xiang Cen, Teng Yuou, Yao Chaoran, Li Xuehui, Cao Menglin, Li Xuzhe, Pan Guojun, Lu Kui, Galons Hervé, Yu Peng
China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science and Technology Tianjin 300457 China
UCTBS, INSERM U1022, Université Paris Descartes 4 Avenue de l'Observatoire 75006 France.
RSC Adv. 2018 Apr 24;8(28):15366-15371. doi: 10.1039/c8ra02523a. eCollection 2018 Apr 23.
Excessive accumulation of free radicals in the body can cause liver damage, aging, cancer, stroke, and myocardial infarction. Anastatin B, a skeletal flavonoid, was reported to have antioxidant and hepatoprotective effects. Anastatin B derivatives, compound 1 and 2, were synthesized by our group previously. In this study, their antioxidant activity and hepatoprotective mechanism were studied using chemical evaluation methods, a cellular model of hydrogen peroxide (HO)-induced oxidative damage, and a mouse model of carbon tetrachloride (CCl)-induced liver injury. Results from the chemical evaluation suggested that both compounds had good antioxidant power and radical scavenging ability . MTT assay showed that both compounds had cytoprotective activity in HO-treated PC12 cells. Moreover, their hepatoprotective activities evaluated using a mouse model of CCl-induced liver injury that compared with the model group, pretreatment with compound 1 and 2 significantly decreased alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), and malondialdehyde (MDA) levels; reduced the liver tissue damage; and increased glutathione content. However, compound 2 was a more effective hepatoprotectant than compound 1 was. Finally, the amount of TNF-α and cytochrome P450 2E1 (CYP2E1) were significantly downregulated in compound 1 and 2 pretreatment groups. Collectively, our findings demonstrate that both compounds have potential antioxidant activity and hepatoprotective effect and . Further chemo-biological study and investigation of the compounds' enzymatic targets are ongoing.
体内自由基的过度积累会导致肝损伤、衰老、癌症、中风和心肌梗死。据报道，骨架黄酮类化合物Anastatin B具有抗氧化和肝脏保护作用。Anastatin B衍生物化合物1和2是我们小组之前合成的。在本研究中，使用化学评估方法、过氧化氢（HO）诱导的氧化损伤细胞模型和四氯化碳（CCl）诱导的肝损伤小鼠模型研究了它们的抗氧化活性和肝脏保护机制。化学评估结果表明，这两种化合物都具有良好的抗氧化能力和自由基清除能力。MTT试验表明，这两种化合物在HO处理的PC12细胞中均具有细胞保护活性。此外，用CCl诱导的肝损伤小鼠模型评估它们的肝脏保护活性，与模型组相比，化合物1和2预处理显著降低了丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、乳酸脱氢酶（LDH）和丙二醛（MDA）水平；减轻了肝组织损伤；并增加了谷胱甘肽含量。然而，化合物2作为肝脏保护剂比化合物1更有效。最后，在化合物1和2预处理组中，肿瘤坏死因子-α（TNF-α）和细胞色素P450 2E1（CYP2E1）的量显著下调。总的来说，我们的研究结果表明这两种化合物都具有潜在的抗氧化活性和肝脏保护作用。对这些化合物的进一步化学生物学研究及其酶靶点的研究正在进行中。
