4.5 Article

Protective Antioxidant Effects of Amentoflavone and Total Flavonoids fromHedyotis diffusaon H2O2-Induced HL-O2 Cells through ASK1/p38 MAPK Pathway

Journal

CHEMISTRY & BIODIVERSITY
Volume 17, Issue 7, Pages -

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbdv.202000251

Keywords

oxidative stress; Hedyotis diffusa; hepatotoxicity; Trx; ASK1/P38 MAPK signaling pathway

Funding

  1. National Natural Science Foundation of China [81973411]
  2. Drug Innovation Major Project [2018ZX09101003001-017]
  3. Shanxi Province Key Research and Development Project [201703D111033]
  4. Project of Center of Comprehensive Development, Utilization and Innovation of Shanxi Medicine [2017-JYXT-18]
  5. Project of Shanxi Key Laboratory for Innovative Drugs on Inflammation-Based Major Disease 'Anti-inflammatory Mechanism of Baihuadexhuangcao Flavone Baogan Capsule' [SXIDL-2018-05]

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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.

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