Abstract
Mitochondrial dysfunction has been identified as one of the primary factors contributing to liver diseases. Pathways that control mitochondrial biogenesis are potential therapeutic targets for the amelioration of hepatocyte dysfunction and liver disease. Research on natural pharmacological agents that ameliorate liver diseases has intensified over the last two decades. Cyanidin-3-glucoside (Cy3g), a dietary flavonoid compound extracted from a wide variety of fruits and vegetables, reportedly has several beneficial health effects. In this study, we used an adult human hepatoma cell line (HuH7) to investigate the effects of the Cy3g polyphenolic compound on mitochondrial function and biogenesis in vitro. An increase in intracellular mitochondrial reductase levels was observed after treatment with Cy3g, but cytotoxicity was not induced. In addition, mitochondrial membrane potential and ATP production were increased following Cy3g treatment. Cy3g treatment also resulted in a dose- and time-dependent upregulation of the gene expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a transcription factor considered a master regulator of mitochondrial biogenesis and metabolism. Additionally, the expression of sirtuin 1 (SIRT1), which plays a key role in deacetylating PGC-1α, was also increased in a dose- and time-dependent manner. Cy3g treatment also increased the expression of downstream PGC-1α genes, nuclear respiratory factor 1 and mitochondrial transcription factor A (TFAM). Our results suggest that Cy3g has potential as a hepatoprotective therapeutic agent that enhances mitochondrial function and biogenesis in hepatocytes.
Highlights
Mitochondria are the main organelles that maintain energy production, control metabolism and regulate stress within cells (Wallace 2005; Nunnari and Suomalainen 2012)
Several studies have reported the beneficial effects of a variety of natural compounds, such as resveratrol, quercetin and catechin on health (Watson et al 2013)
Cy3g, a phenol pigment that belongs to the flavonoid family, has been shown to have beneficial effects in several in vitro and in vivo clinical trials (Watson et al 2013)
Summary
Mitochondria are the main organelles that maintain energy production, control metabolism and regulate stress within cells (Wallace 2005; Nunnari and Suomalainen 2012). Mitochondrial health is an important parameter of overall cell health. Mitochondrial dysfunction has been found to be a key factor leading to the development of a variety of diseases, such as neurodegenerative disorders (Johri and Beal 2012), endocrine dysfunction (Chow et al 2016), and several metabolic disorders, such as insulin resistance (Petersen et al 2003; Morino et al 2006), as well as hepatic and cardiovascular diseases (Gustafsson and Gottlieb 2007; Nassir and Ibdah 2014). Disrupted hepatocyte metabolism results in lipid retention in hepatocytes. This retention has been attributed to failed long chain fatty acid catabolism via hepatic mitochondrial beta-oxidation (Fabbrini et al 2010)
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