Abstract

The fruits of Ailanthus altissima Swingle (AS) possess a variety of pharmacological activities. Its antioxidant activity and the potential mode of action have not yet been investigated. In in vitro studies, AS revealed the strong reducing power and DPPH scavenging effect, but hydroxyl radical scavenging activity and ferrous ions-chelating ability were not strong. Meanwhile, the oxidative stress RAW264.7 cell injury model was established, the low and medium-doses of AS showed significant protective effects on the viability of H2O2-treated cells by CCK-8 method. Besides, three doses of AS all increased the activities of SOD, CAT, and GSH-Px and decreased the MDA level compared with the H2O2 group, suggesting it significantly relieved oxidative stress of cells. The active ingredients and related targets of AS were collected by HERB and Swiss Target Prediction database, the common targets of drugs and diseases database were conducted by GeneCards database platform and the Venny platform. We screened the core targets of AS like threonine kinase1 (AKT1), mitogen-activated protein kinase 1 (MAPK1), sirtuin-1 (SIRT1), mechanistic target of rapamycin kinase (MTOR) by STRING database, and the key pathways involved PI3K-AKT and FoxO signaling pathway by KEGG pathway enrichment analysis. Besides, qRT-PCR revealed AS preconditioning significantly up-regulated the expression level of AKT1, SIRT1, MAPK1, and MTOR in model cells, and the effect was related to the regulation of FoxO and PI3K/AKT signaling pathway. In summary, AS showed significant antioxidant activity and its potential mechanism was regulating FoxO and PI3K/AKT signaling pathway.

Highlights

  • Oxidative stress is the imbalance between oxidation and antioxidant reaction caused by the accumulation of free radicals in the body [1]

  • The results showed the expression levels of AS like threonine kinase1 (AKT1), mitogen-activated protein kinase 1 (MAPK1), SIRT1, and mechanistic target of rapamycin kinase (MTOR) in the model group were significantly upregulated compared with the normal group (p < 0.05)

  • The present study investigated the in vitro and intracellular antioxidant activity of altissima Swingle (AS), and the potential antioxidant mechanism based on network pharmacology

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Summary

Introduction

Oxidative stress is the imbalance between oxidation and antioxidant reaction caused by the accumulation of free radicals in the body [1]. Cells produce free radicals through multiple metabolic pathways, and free radicals are crucial factors that give rise to oxidative damage of proteins, showing high reactivity [2]. Reactive oxygen species (ROS) are the uppermost free radicals in Antioxidant Activity & Mechanism of AS cells and mainly produced by mitochondria [3]. Excess ROS break down cells and tissues, affect metabolic function, and cause different health problems [4]. Previous studies have indicated that oxidative damage to proteins caused by ROS has something to do with aging, the occurrence of atherosclerosis, arthritis, cancer, and neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease [5,6,7]. Cells maintain ROS homeostasis through superoxide dismutase (SOD) system, catalase (CAT) system, glutathione peroxidase (GSH-Px) system, etc. [8]

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