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Tryptanthrin Prevents Oxidative Stress-Mediated Apoptosis Through AMP-activated Protein Kinase-Dependent p38 Mitogen-Activated Protein Kinase Activation

Tryptanthrin Prevents Oxidative Stress-Mediated Apoptosis Through AMP-activated Protein Kinase-Dependent p38 Mitogen-Activated Protein Kinase Activation

Eun Hye Jung, Ji Yun Jung, Hae Li Ko, Jae Kwang Kim, Sang Mi Park, Dae Hwa Jung, Chung A Park, Young Woo Kim, Sae Kwang Ku, Il Je Cho, Sang Chan Kim

Arch Pharm Res. 2017 Sep;40(9):1071-1086.

PMID: 28828587

Abstract:

Tryptanthrin (6,12-dihydro-6,12-dioxoindolo-(2,1-b)-quinazoline) has been reported to have a variety of pharmacological activities. Present study investigated the cytoprotective effects of tryptanthrin on arachidonic acid (AA) + iron-mediated oxidative stress and the molecular mechanisms responsible. In HepG2 cells, pretreatment with tryptanthrin inhibited the cytotoxic effect of AA + iron in a concentration-dependent manner. In addition, tryptanthrin prevented the changes in the levels of apoptosis-related proteins, and attenuated reactive oxygen species production, glutathione depletion, and mitochondrial membrane impairment induced by AA + iron. Mechanistic investigations showed that tryptanthrin increased the phosphorylations of AMP-activated protein kinase (AMPK) and of p38 mitogen-activated protein kinase (p38). Furthermore, inhibition of AMPK or p38 reduced the ability of tryptanthrin to prevent AA + iron-induced cell death and mitochondrial dysfunction. Transfection experiments using AMPK mutants indicated that p38 phosphorylation by tryptanthrin was dependent on AMPK activation. In a phenylhydrazine-induced acute liver injury model, tryptanthrin decreased serum levels of alanine aminotransferase, aspartate aminotransferase, and bilirubin in mice. Additionally, tryptanthrin reduced numbers of degenerating hepatocytes, infiltrating inflammatory cells, 4-hydroxynonenal-, and nitrotyrosine-positive cells in hepatic tissues. Thus, these results suggest tryptanthrin has therapeutic potential to protect cells from oxidative injury via AMPK-dependent p38 activation.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP13220570-B	Tryptanthrin		13220-57-0	Price

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