Revealing the anti-inflammatory mechanism and effective constituents of Hosta plantaginea flowers by a strategy integrating network pharmacology, molecular docking, and experimental verification

Abstract

IntroductionInflammation is a common cause of illness among outpatients, but effective drugs are extremely scarce. Hosta plantaginea flower is an important herbal medicine in China that treats inflammation-related diseases, but its anti-inflammatory mechanism remains unclear. MethodsSystematic network pharmacology was employed to decipher H. plantaginea flower's anti-inflammatory hub targets and candidate phytochemicals. Furthermore, molecular docking was used to elucidate the interaction of constituents and targets. Afterward, the anti-inflammatory activity of H. plantaginea flower and its mechanism were validated in RAW264.7 cells activated by lipopolysaccharide (LPS). ResultsH. plantaginea flower contains 153 phytochemicals, of which 85 were potential effective constituents. 949 H. plantaginea flower targets and 814 inflammation-related targets were predicted, of which 211 intersecting targets were acquired. Six major constituents, including corvitin, phytyldiol, agapanthagenin, 5,7-dimethoxy-8-methyl-4′-hydroxyflavan, (3R)-2,3-dihydro-7-hydroxy-3-[(4-methoxyphenyl)methyl]-4H-1-benzopyran-4-one, and phenol, 4-[(2S)-3,4-dihydro-5,7-dimethoxy-2H-1-benzopyran-2-yl] were picked out. Furthermore, 6 hub targets such as C-type lectin-like receptor 2 (CLEC1B), toll-like receptor (TLR), tumor necrosis factor (TNF), recombinant V-Rel reticuloendotheliosis viral oncogene homolog A (RELA), signal transducer and activator of transcription 3 (STAT3), and protein kinase B α (AKT1) were obtained using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional analyses. Molecular docking indicated that these 6 constituents had strong binding abilities with these 6 hub targets. Finally, the anti-inflammatory effect of H. plantaginea flower and its mechanism were verified in LPS-induced RAW264.7 cells by the inhibition of CLEC1B, TLR-4, TNF-α, STAT3, and Akt1 proteins, thereby suppressing the overproduction of nitric oxide. ConclusionH. plantaginea flower exerted a significant anti-inflammatory activity by suppressing TLR-4 and CLEC1B signaling pathways, which was elucidated and validated by an integrated strategy based on network pharmacology, molecular docking, and experimental verification. Collectively, this study provides a novel insight into the pharmacodynamics and mechanisms of H. plantaginea flower as a promising agent in treating inflammation-related disease.