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Background: Escin is the main active component in Aesculus hippocastanum. It has been demonstrated that escin has anti-inflammatory properties. This study combined the methods of network pharmacology, molecular docking, and molecular dynamics to explore the molecular mechanism of escin against neuropathic pain (NP). Methods: The Swiss Target Prediction and the Pharm Mapper database were employed for predicting the targets of escin. Also, the candidate targets of NP were gathered via the databases including Therapeutic Targets, DisGeNet, GeneCards, DrugBank, and OMIM. Subsequently, the network of protein-protein interaction was screened for the key targets by the software Cytoscape 3.8.0. Then, the intersection of these targets was analysed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Additionally, we further investigated the ligand-target interactions by molecular docking and molecular dynamics simulations. Results: In total, 94 escin targets were predicted by network pharmacology. Among them, SRC, MMP9, PTGS2, and MAPK1 were the core candidate targets. Subsequently, the analysis of GO and KEGG enrichment revealed that escin affected NP by regulating protein kinase C, MAP kinase, TRP channels, the T-cell receptors signaling pathway, and the TNF signaling pathway. The results of molecular docking and molecular dynamics simulation confirmed that escin not only had a strong binding activity with the four core target proteins but also stably combined in 50 ns. Conclusions: Our study revealed that escin acts on the core targets SRC, MMP9, PTGS2, MAPK1, and associated enrichment pathways to alleviate neuronal inflammation and regulate the immune response, thus exerting anti-NP efficacy. This study provided innovative ideas and methods for the promising treatment of escin in relieving NP.
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ETHNOPHARMACOLOGICAL RELEVANCE: Modified Dingchuan Decoction (MDD) is a Chinese medicine formula containing 11 materials with cough suppression, asthma relief, and anti-inflammatory effects. AIM OF THE STUDY: This study aimed to evaluate the therapeutic effect of MDD on cough-variant asthma (CVA) and to investigate its mechanism of action. MATERIALS AND METHODS: The chemical constituents of MDD were analyzed by ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap HRMS). A guinea pig CVA model was established using an intramuscular injection of ovalbumin (OVA), combined with an intraperitoneal injection of aluminum hydroxide [Al(OH)3] and nebulized OVA. At the beginning of day 18, the low, medium, and high MDD groups were gavaged with 7.23 g/kg, 14.46 g/kg, and 28.92 g/kg of MDD, respectively, and the positive group was gavaged with 5 mg/kg of prednisone acetate combined with 1 mg/kg of montelukast sodium; the normal and model groups were given an equal volume of distilled water, once a day for 21 days. The cough was induced by 10-3 mol/L capsaicin solution 1 h after the last administration, and the number of coughs and the latency of coughs were evaluated. Hematoxylin and eosin staining (H&E) was used to observe pathological changes in the lungs and airways. The concentration of inflammatory factors in bronchoalveolar lavage fluid (BALF) was measured by enzyme-linked immunosorbent assay (ELISA). We analyzed the lung microbiota using 16 S ribosomal DNA (16 S rDNA) high-throughput sequencing. RESULTS: The 38 chemical components were found in MDD, and MDD reduced the number of coughs in guinea pigs with CVA, prolonged cough latency, improved pathological damage to the lungs and airways, regulated inflammatory factor levels in BALF, and modulated the lung microbiota. CONCLUSIONS: This study demonstrated that treating CVA with MDD may be related to inhibiting lung inflammation and regulating lung microbiota.