Lee Kyung-Mi, Kwon Tae Yeon, Kang Unwoo, Seo Eun Kyoung, Yun Ji Ho, Nho Chu Won, Kim Yeong Shik
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, South Korea.
College of Pharmacy, Graduate School of Pharmaceutical Sciences (Ewha Global Top 5 Program), Ewha Womans University, Seoul 03760, South Korea.
Food Chem Toxicol. 2017 Oct;108(Pt A):120-127. doi: 10.1016/j.fct.2017.07.035. Epub 2017 Jul 18.
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.
款冬酮是一种从药用植物款冬中提取的化合物，款冬作为一种传统药物用于治疗包括哮喘和肺炎在内的呼吸道疾病。最近的报道表明款冬酮具有抗炎作用；然而，其保护功能的范围尚未阐明。在本研究中，我们证明款冬酮通过增加Hepa1c1c7细胞中的醌还原酶活性来增强细胞解毒作用。此外，款冬酮降低了叔丁基过氧化氢（t-BHP）诱导的活性氧生成和细胞死亡，表明它还作为一种有效的抗氧化剂发挥作用。为了验证款冬酮活性的分子机制，我们检测了核因子红细胞2相关因子2（Nrf2）的表达，Nrf2是一种调节抗氧化蛋白表达的转录因子，在HepG2细胞中进行检测。值得注意的是，这些结果表明款冬酮诱导Nrf2激活和核积累，导致解毒酶NAD（P）H醌脱氢酶1（NQO1）和血红素加氧酶-1（HO-1）上调，从而保护细胞免受氧化应激。进一步的分子分析表明，款冬酮诱导的Nrf2激活在HepG2细胞中是由ERK1/2介导的。总的来说，这些数据表明款冬酮通过Nrf2途径激活和靶基因表达减轻t-BHP诱导的活性氧，并激活醌还原酶活性，从而作为一种抗氧化剂保护HepG2细胞免受氧化应激和相关损伤。
