Vasorelaxant Activities and its Underlying Mechanisms of Magnolia Volatile Oil on Rat Thoracic Aorta Based on Network Pharmacology

Abstract

Objective: Magnolia volatile oil (MVO) is a mixture mainly containing eudesmol and its isomers. This study was to investigate the vasorelaxant effects and the underlying mechanism of MVO in rat thoracic aortas.Method: The present study combined gas chromatography–mass spectrometry (GC-MS) and network pharmacology analysis with in vitro experiments to clarify the mechanisms of MVO against vessel contraction. A compound–target network, compound–target–disease network, protein–protein interaction network, compound–target–pathway network, gene ontology, and pathway enrichment for hypertension were applied to identify the potential active compounds, drug targets, and pathways. Additionally, the thoracic aortic rings with or without endothelium were prepared to explore the underlying mechanisms. The roles of the PI3K-Akt-NO pathways, neuroreceptors, K+ channels, and Ca2+ channels on the vasorelaxant effects of MVO were evaluated through the rat thoracic aortic rings.Results: A total of 29 compounds were found in MVO, which were identified by GC-MS, of which 21 compounds with a content of more than 0.1% were selected for further analysis. The network pharmacology research predicted that beta-caryophyllene, palmitic acid, and (+)-β-selinene might act as the effective ingredients of MVO for the treatment of hypertension. Several hot targets, mainly involving TNF, CHRM1, ACE, IL10, PTGS2, REN, and F2, and pivotal pathways, such as the neuroactive ligand–receptor interaction, the calcium signaling pathway, and the PI3K-Akt signaling, were responsible for the vasorelaxant effect of MVO. As expected, MVO exerted a vasorelaxant effect on the aortic rings pre-contracted by KCl and phenylephrine in an endothelium-dependent and non-endothelium-dependent manner. Importantly, a pre-incubation with indomethacin (Indo), N-nitro-L-arginine methyl ester, methylene blue, wortmannin, and atropine sulfate as well as 4-aminopyridione diminished MVO-induced vasorelaxation, suggesting that the activation of the PI3K-Akt-NO pathway and KV channel were involved in the vasorelaxant effect of MVO, which was consistent with the results of the Kyoto Encyclopedia of Genes and the Genomes. Additionally, MVO could significantly inhibit Ca2+ influx resulting in the contraction of aortic rings, revealing that the inhibition of the calcium signaling pathway exactly participated in the vasorelaxant activity of MVO as predicted by network pharmacology.Conclusion: MVO might be a potent treatment of diseases with vascular dysfunction like hypertension. The underlying mechanisms were related to the PI3K-Akt-NO pathway, KV pathway, as well as Ca2+ channel, which were predicted by the network pharmacology and verified by the experiments in vitro. This study based on network pharmacology provided experimental support for the clinical application of MVO in the treatment of hypertension and afforded a novel research method to explore the activity and mechanism of traditional Chinese medicine.

Improved effect of fresh ginseng paste (radix ginseng-ziziphus jujube) on hyperuricemia based on network pharmacology and molecular docking

“…XO is the critical enzyme in the last step of UA synthesis, which catalyzes the oxidation of hypoxanthine to xanthine and then to UA, or directly to UA ( Furuhashi et al, 2018 ; Kawachi et al, 2021 ). Several studies have shown that flavonoids ( Scheepers et al, 2019 ) and saponins ( Xu et al, 2022 ) isolated from TCM can reduce UA by reducing the content of XO in the liver while enhancing renal excretion of UA. Meanwhile, previous reports have shown that Urtica extracts can reduce serum UA levels by improving renal metabolism ( Liu et al, 2020 ).…”

Exploring the chemical composition, medicinal benefits, and antioxidant activity of Plumula nelumbinis essential oil from different habitats in China

“…To further understand the potential mechanisms of the antioxidant effects of the active components in the PNEO, a network pharmacology approach was used to predict the relevant targets of the compounds. First of all, the compounds regulate SMILES information from PubChem ( https://pubchem.ncbi.nlm.nih.gov/ ) and used to search the SwissTargetPrediction web server ( https://swisstargetprediction.ch/ ) for human target prediction (Probability*>0.1)( Xu et al, 2022 ).…”

“…For the analysis of the PNEO in antioxidant pharmacological mechanism, using DAVID 6.7 database ( https://david.ncifcrf.gov/ ) has carried on the enrichment of Gene Ontology (GO), including cell composition, molecular function and biological processes ( Jiao et al, 2022 ). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed using the Metascape database ( https://metascape.org ) ( Xu et al, 2022 ). Finally, R Studio was used for drawing.…”