Research Paper|Volume 13, Issue 16|pp 20050—20080

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

Anastasiya Lipatova¹, George Krasnov^1,², Pavel Vorobyov¹, Pavel Melnikov³, Olga Alekseeva¹, Yulia Vershinina¹, Alexander Brzhozovskiy⁴, Daria Goliusova⁵, Faniya Maganova⁶, Natalia Zakirova^1,², Anna Kudryavtseva^1,², Alexey Moskalev^1,^7,⁸

¹Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia
²Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia
³V. Serbsky National Research Center for Psychiatry and Narcology, Moscow 119034, Russia
⁴Skolkovo Institute of Science and Technology, Moscow 121205, Russia
⁵Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119991, Russia
⁶Initium-Pharm, LTD, Moscow 142000, Russia
⁷Institute of Biology of Federal Research Center “Komi Science Center” of Ural Branch of RAS, Syktyvkar 167982, Russia
⁸Russian Clinical and Research Center of Gerontology, Moscow 129226, Russia

Received: July 27, 2020Accepted: July 23, 2021Published: August 24, 2021

https://doi.org/10.18632/aging.203448

Copyright: © 2021 Lipatova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.