Effects of the Phytochemical Combination PB123 on Nrf2 Activation, Gene Expression, and the Cholesterol Pathway in HepG2 Cells

There has been a long history of human usage of the biologically-active phytochemicals in Salvia rosmarinus, Zingiber officinale, and Sophora japonica for health purposes, and we recently reported on a combination of those plant materials as the PB123 dietary supplement. In the present work we extended those studies to evaluate activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor and differential gene expression in cultured HepG2 (hepatocellular carcinoma) cells treated with PB123. We determined transcriptome changes using mRNA-seq methods, and analyzed the affected pathways using Ingenuity Pathway Analysis and BioJupies, indicating that primary effects included increasing the Nrf2 pathway and decreasing the cholesterol biosynthesis pathway. Pretreatment of cultured HepG2 cells with PB123 upregulated Nrf2-dependent cytoprotective genes and increased cellular defenses against cumene hydroperoxide-induced oxidative stress. In contrast, pretreatment of cultured HepG2 cells with PB123 downregulated cholesterol biosynthesis genes and decreased cellular cholesterol levels. These findings support the possible beneficial effects of PB123 as a healthspan-promoting dietary supplement.