Effects of Siberian fir terpenes extract Abisil on antioxidant activity, autophagy, transcriptome and proteome of human fibroblasts

Background: Abisil is an extract of Siberian fir terpenes with antimicrobial and wound healing activities. Previous studies revealed that Abisil has geroprotective, anti-tumorigenic, and anti-angiogenic effects. Abisil decreased the expression of cyclin D1, E1, A2, and increased the phosphorylation rate of AMPK. Objective: In the present study, we analyzed the effect of Abisil on autophagy, the mitochondrial potential of embryonic human lung fibroblasts. We evaluated its antioxidant activity and analyzed the transcriptomic and proteomic effects of Abisil treatment. Results: Abisil treatment resulted in activation of autophagy, reversal of rotenone-induced elevation of reactive oxygen species (ROS) levels and several-fold decrease of mitochondrial potential. Lower doses of Abisil (25 μg/ml) showed a better oxidative effect than high doses (50 or 125 μg/ml). Estimation of metabolic changes after treatment with 50 μg/ml has not shown any changes in oxygen consumption rate, but extracellular acidification rate decreased significantly. Abisil treatment (5 and 50 μg/ml) of MRC5-SV40 cells induced a strong transcriptomic shift spanning several thousand genes (predominantly, expression decrease). Among down-regulated genes, we noticed an over-representation of genes involved in cell cycle progression, oxidative phosphorylation, and fatty acid biosynthesis. Additionally, we observed predominant downregulation of genes encoding for kinases. Proteome profiling also revealed that the content of hundreds of proteins is altered after Abisil treatment (mainly, decreased). These proteins were involved in cell cycle regulation, intracellular transport, RNA processing, translation, mitochondrial organization. Conclusions: Abisil demonstrated antioxidant and autophagy stimulating activity. Treatment with Abisil results in the predominant downregulation of genes involved in the cell cycle and oxidative phosphorylation.