Exploration of the mechanism of luteolin against ischemic stroke based on network pharmacology, molecular docking and experimental verification

Abstract

Stroke is a leading cause of morbidity and mortality worldwide. As the most common type of stroke cases, treatment effectiveness is still limited despite intensive research. Recently, traditional Chinese medicine has attracted attention because of potential benefits for stroke treatment. Among these, luteolin, a natural plant flavonoid compound, offers neuroprotection following against ischemic stroke, although the specific mechanisms are unknown. Here we used network pharmacology, molecular docking, and experimental verification to explore the mechanisms whereby luteolin can benefit stroke recovery. The pharmacological and molecular properties of luteolin were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The potential targets of luteolin and ischemic stroke were collected from interrogating public databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed by Funrich and Database for Annotation, Visualization and Integrated Discovery respectively, a luteolin-target-pathway network constructed using Cytoscape, Autodock vina was used for molecular docking simulation with Discovery Studio was used to visualize and analyze the docked conformations. Lastly, we employed an in vitro model of stroke injury to evaluate the effects of luteolin on cell survival and expression of the putative targets. From 95 candidate luteolin target genes, our analysis identified six core targets . KEGG analysis of the candidate targets identified that luteolin provides therapeutic effects on stroke through TNF signaling and other pathways. Our experimental analyses confirmed the conclusions analyzed above. In summary, the molecular and pharmacological mechanisms of luteolin against stroke are indicated in our study from a systematic perspective.

Study on the Mechanism of Zhilong Huoxue Tongyu Capsule in the Treatment of Ischemic Stroke Based on Network Pharmacology and Molecular Docking Technology

“…It may have a therapeutic effect on stroke through TNF signaling. Rholin has been shown to combat ischemia and reperfusion injury, reducing the size of the infarcted area in experimental models [13] . Ursolic acid regulates TLR signaling and exhibits significant anti-inflammatory properties, which can reduce the production of inflammatory cytokines through the High Mobility Group Box 1 (HMGB1)/TLR4/Nuclear Factor Kappa B (NF-κB) signaling pathway to protect the brain from cerebral ischemia and reperfusion injury [14] .…”

Exploration of the Core Pathways and Potential Targets of Luteolin Treatment on Late-Onset Depression Based on Cerebrospinal Fluid Proteomics

“…Thus, it is quite appropriate to adopt GSEA for investigating the possible pathways and potential targets of LUT for LOD treatment. Molecular docking simulations predict affinity and binding modes through ligand–receptor interactions, which helps to provide a reliable basis for experiment-based assays, thereby accelerating drug design and selection [ 35 ]. Consequently, mechanistic studies of LUT against LOD, based on proteomics, GSEA, and molecular docking to simulate natural compound–target binding, can provide a foundation for the development of targeted drugs for LOD.…”

Researching the molecular mechanisms of Taohong Siwu Decoction in the treatment of varicocele-associated male infertility using network pharmacology and molecular docking: A review

“…In order to find the core genes of network, Cytoscape 3.9.1 software was used for PPI network diagram visualization. The node whose degree were greater than the average value were AKT1 (37), TNF (37), ALB (37), TP53 (36), VEGFA (36), IL6 (35), HIF1A (34),CASP3 (33), ESR1 (33), CAT (32), PTGS2 (32), HSP90AA1 (31), EGFR (30), MTOR (30), PTEN (30), HMOX1 (28), NOS3 (28), CASP8 (28), MMP9 (27), CASP9 (24), and SOD1 (23) (Fig. 3B), which may play an important role in the treatment of THSWD with varicocele-associated male infertility.…”

“…Luteolin is a kind of natural brass, and numerous studies have shown that it has anti-inflammatory, antioxidant, and anti-cancer biological activities. [31][32][33] Boeing et al [34] found that luteolin could reduce the oxidative stress response caused by iritantan by reducing reactive oxygen species and enhancing endogenous antioxidants. It also alleviated inflammation by reducing TNF, IL-1β and IL-6 levels and increasing IL-4 and IL-10 levels.…”