Network pharmacological prediction on metabolites of dominant endophytic strains from Salvia plebeia R. Br

Salvia plebeia R. Br. exerts favorable therapeutic effects on multiple diseases such as bronchitis, urticaria and colorectal cancer. Endophytes play vital roles in the growth and development of medicinal plants. They can not only promote plant growth, but also synthesize active ingredients identical to those of host plants, as well as induce hosts to produce active components. For the first time, this study systematically investigated the endophytes of S. plebeia. We evaluated the antagonistic activity and plant growth-promoting traits of endophytes, explored the bacteriostatic effects of strain fermentation broths and volatile organic compounds, and screened strains with excellent functional properties. Headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS) was adopted to analyze the differences in metabolic components between S. plebeia and its dominant endophytes. Combined with network pharmacology, we further elucidated the potential molecular mechanisms by which their active ingredients intervene in diseases. Network pharmacology analysis revealed that S. plebeia and its dominant endophytes share a variety of active metabolites, which exert synergistic regulatory effects through common core targets and key signaling pathways. Meanwhile, endophytes possess unique regulatory pathways, a more complex protein-protein interaction network and stronger target binding capacity. They perform medicinal functions via a synergistic mode of multiple components, multiple targets and multiple pathways. This is the first study to apply network pharmacology to predict the correlation of metabolic components between endophytes and their host plants.