Extract of Siberian fir terpenes Abisil demonstrates antioxidant activity and induces both mitophagy and autophagy

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 decreases expression of cyclin D1, E1, A2 and increases the phosphorylation rate of AMPK.Objective. In the present study, we analyzed the effect of Abisil on mito- and autophagy, mitochondrial potential. We evaluated its antioxidant activity and analyzed transcriptomic and proteomic effect of Abisil treatment.Results. Abisil treatment resulted in 2-fold decrease of mitochondrial potential, dose-dependent increase of autophagy and mitophagy rates (up to 10-fold; MRC5/SV40 and LECH-4 cells). Abisil reverted rotenone-induced elevation of ROS levels. Surprisingly, in oxidative stress assays, lower doses of Abisil (25 mkg/ml) showed better effect than high doses (50 or 125 mkg/ml).Abisil treatment (5 and 50 mkg/ml) of MRC5/SV40 cells induced strong transcriptomic shift spanning thousand genes (predominantly, expression decrease). Among downregulated genes, we noticed 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 (especially at 5 mkg/ml). 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. Among top altered proteins with decreased level we noticed mTOR and RICTOR.Conclusions. Abisil, an extract of Abies Sibirica resins, demonstrated antioxidant, mito- and autophagy stimulating activity. Treatment with Abisil results in predominant downregulation of genes involved in cell cycle and oxidative phosphorylation. In general, treatment in a low concentration (5 or 25 mkg/ml) in several aspects gives a better effect than treatment in high doses (50 or 125 mkg/ml).