Abstract
Oxidative stress is the redox imbalance state of organisms that involves in a variety of biological processes of diseases. Limonium aureum (L.) Hill. is an excellent wild plant resource in northern China, which has potential application value for treating oxidative stress. However, there are few studies that focused on the antioxidant effect and related mechanism of L. aureum. Thus, the present study combining systematic network pharmacology and molecular biology aimed to investigate the antioxidant effects of L. aureum and explore its underlying anti-oxidation mechanisms. First, the antioxidant activity of L. aureum extracts was confirmed by in vitro and intracellular antioxidant assays. Then, a total of 11 bioactive compounds, 102 predicted targets, and 70 antioxidant-related targets were obtained from open source databases. For elucidating the molecular mechanisms of L. aureum, the PPI network and integrated visualization network based on bioinformatics assays were constructed to preliminarily understand the active compounds and related targets. The subsequent enrichment analysis results showed that L. aureum mainly affect the biological processes involving oxidation-reduction process, response to drug, etc., and the interference with these biological processes might be due to the simultaneous influence on multiple signaling pathways, including the HIF-1 and ERBB signaling pathways. Moreover, the mRNA levels of predicted hub genes were measured by qRT-PCR to verify the regulatory effect of L. aureum on them. Collectively, this finding lays a foundation for further elucidating the anti-oxidative damage mechanism of L. aureum and promotes the development of therapeutic drugs for oxidative stress.
Highlights
Oxidative stress is the redox imbalance state of organisms, which is caused by the produced amount of reactive nitrogen or reactive oxygen radicals beyond its scavenging range when organisms are stimulated [1]
Network pharmacology integrates information obtained by computational methods including graph theory, statistics approaches, data mining, modeling, information visualization, etc., and information obtained by experimental methods including various high-throughput omics techniques, biological and pharmacological experiments, etc
As an emerging field based on systems pharmacology, systematic network pharmacology plays an important role in understanding the molecular mechanisms of traditional Chinese medicine in the treatment of complex diseases and is a promising tool for natural drug development
Summary
Oxidative stress is the redox imbalance state of organisms, which is caused by the produced amount of reactive nitrogen or reactive oxygen radicals beyond its scavenging range when organisms are stimulated [1]. Many environmental stimuli, including UV, ionizing radiation, chemotherapeutics, heavy metals, and environmental toxins, can trigger the high levels production of reactive oxygen. Related mechanisms of the redox balance maintenance are critical to the treatment of oxidative stress diseases and have become the research hotspots in recent years. Network pharmacology is the theory based on systems biology, which was proposed by Hopkins [9, 10] in 2007. The basic processes of network pharmacology analysis include analysis of candidate ingredients, database construction of target disease, prediction of key targets, network analysis, enrichment analysis, and verification of predicted targets [15,16,17]. As an emerging field based on systems pharmacology, systematic network pharmacology plays an important role in understanding the molecular mechanisms of traditional Chinese medicine in the treatment of complex diseases and is a promising tool for natural drug development
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