Modulation of mitochondrial activity by sugarcane (Saccharum officinarum L.) top extract and its bioactive polyphenols: a comprehensive transcriptomics analysis in C2C12 myotubes and HepG2 hepatocytes

Abstract

Age-related mitochondrial dysfunction leads to defects in cellular energy metabolism and oxidative stress defense systems, which can contribute to tissue damage and disease development. Among the key regulators responsible for mitochondrial quality control, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is an important target for mitochondrial dysfunction. We have previously reported that bioactive polyphenols extracted from sugarcane top (ST) ethanol extract (STEE) could activate neuronal energy metabolism and increase astrocyte PGC-1α transcript levels. However, their potential impact on the mitochondria activity in muscle and liver cells has not yet been investigated. To address this gap, our current study examined the effects of STEE and its polyphenols on cultured myotubes and hepatocytes in vitro. Rhodamine 123 assay revealed that the treatment with STEE and its polyphenols resulted in an increase in mitochondrial membrane potential in C2C12 myotubes. Furthermore, a comprehensive examination of gene expression patterns through transcriptome-wide microarray analysis indicated that STEE altered gene expressions related to mitochondrial functions, fatty acid metabolism, inflammatory cytokines, mitogen-activated protein kinase (MAPK) signaling, and cAMP signaling in both C2C12 myotubes and HepG2 hepatocytes. Additionally, protein–protein interaction analysis identified the PGC-1α interactive-transcription factors-targeted regulatory network of the genes regulated by STEE, and the quantitative polymerase chain reaction results confirmed that STEE and its polyphenols upregulated the transcript levels of PGC-1α in both C2C12 and HepG2 cells. These findings collectively suggest the potential beneficial effects of STEE on muscle and liver tissues and offer novel insights into the potential nutraceutical applications of this material. Graphical Abstract