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Food Chem Toxicol. 2017 Oct;108(Pt A):120-127. doi: 10.1016/j.fct.2017.07.035. Epub 2017 Jul 18.

Tussilagonone-induced Nrf2 pathway activation protects HepG2 cells from oxidative injury.

Author information

1
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, South Korea.
2
College of Pharmacy, Graduate School of Pharmaceutical Sciences (Ewha Global Top 5 Program), Ewha Womans University, Seoul 03760, South Korea.
3
Convergence Research Center for Smart Farm Solution, Korea Institute of Science and Technology, Gangneung 25451, South Korea.
4
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, South Korea. Electronic address: kims@snu.ac.kr.

Abstract

Tussilagonone is a compound derived from the medicinal plant Tussilago farfara L., which is used as a traditional medicine for respiratory diseases, including asthma and pneumonia. Recent reports suggest that tussilagonone exhibits anti-inflammatory effects; however, the scope of protective functions has not been elucidated yet. In this study, we demonstrate that tussilagonone enhances cellular detoxification by increasing quinone reductase activity in Hepa1c1c7 cells. In addition, tussilagonone decreased tert-butyl hydroperoxide(t-BHP)-induced ROS production and cell death, suggesting that it also acts as a potent antioxidant. To verify the molecular mechanism underlying tussilagonone activity, we examined the expression of nuclear factor erythroid 2-related factor 2(Nrf2)-a transcription factor that regulates antioxidant protein expression-in HepG2 cells. Significantly, these results showed that tussilagonone induces Nrf2 activation and nuclear accumulation, resulting in the upregulation of the detoxifying enzymes NAD(P)H quinone dehydrogenase 1(NQO1) and heme oxygenase-1(HO-1) that protect cells from oxidative stress. Further molecular analyses revealed that tussilagonone-induced Nrf2 activation was mediated by ERK1/2 in HepG2 cells. Collectively, these data indicate that tussilagonone attenuates t-BHP-induced ROS and activates quinone reductase activity via Nrf2 pathway activation and target gene expression, and thereby acts as an antioxidant that protects HepG2 cells from oxidative stress and associated damage.

KEYWORDS:

ERK1/2; Hepatoprotective effect; Nrf2; Oxidative injury; Tussilagonone

PMID:
28733231
DOI:
10.1016/j.fct.2017.07.035
[Indexed for MEDLINE]

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