Protective Antioxidant Effects of Amentoflavone and Total Flavonoids fromHedyotis diffusaon H2O2-Induced HL-O2 Cells through ASK1/p38 MAPK Pathway
Protective Antioxidant Effects of Amentoflavone and Total Flavonoids fromHedyotis diffusaon H2O2-Induced HL-O2 Cells through ASK1/p38 MAPK Pathway
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DOI：
10.1002/cbdv.202000251
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发表时间：
2020-06-17
影响因子：
2.9
通讯作者：
Li, Qing-Shan
中科院分区：
文献类型：
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作者：
Li, Yun-Lan;Chen, Xi;Li, Qing-Shan
本研究采用乙酸乙酯提取白花蛇舌草中的总黄酮酸和总三萜酸，并测定了它们和5种总黄酮类化合物对H(2)O(2)诱导的HL-02细胞肝损伤的保护作用。特别是对谷丙转氨酶、谷草转氨酶、乳酸脱氢酶漏出量、超氧化物歧化酶活性和丙二醛含量的影响。它们有效地减少了肝细胞中基质金属蛋白酶的丢失，细胞色素C的释放，进而抑制了caspase-3/caspase-9级联反应的激活。氨基黄酮组和类黄酮组的ROS含量明显降低，抑制了p38的表达，从而通过增加硫氧还蛋白Trx1和还原酶TrxR1来降低ASK1和p-p38的水平。这些结果提示，双黄酮类化合物的抗氧化保护作用可能是通过增加Trx1和TrxR1的水平来降低ROS，从而抑制H_2O_2诱导的途径上游，而Trx_1和Trx_1在阻断ASK1/p38 MAPK途径的下游效应和减轻肝毒性中起着关键作用。
In this study, total flavonoids and total triterpenoid acid were extracted with ethyl acetate fromHedyotis diffusaWilld, and hepatoprotective activities of them and five compounds from total flavonoids against H(2)O(2)induced hepatocyte damage on HL-02 cells were determined. In particular, amentoflavone and total flavonoids had influence on the leakage of ALT, AST, LDH, the activities of SOD and the content of MDA. They effectively reduced the loss of MMP, the release of Cyt C, and then inhibited activation of caspase-3/caspase-9 cascade in hepatotoxic cells. The contents of ROS were significantly reduced to inhibit p38 in amentoflavone and flavonoids groups which decreased ASK1 and p-p38 levels through increasing thioredoxin Trx1 and reductase TrxR1. These results suggesting that the antioxidant protection of amentoflavone and flavonoids might be reducing ROS to inhibit the H2O2-induced upstream of pathway via increasing levels of Trx1 and TrxR1, which were pivotal in blocking the down streaming effectors of ASK1/p38 MAPK pathway and alleviating hepatotoxicity.