AUTHOR=Lou Tian-ling , Ji Tao , Peng Xin , Ji Wei-wei , Yuan Li-xia , Wang Juan , Li Shi-min , Zhang Shun , Shi Qiao-yun 

TITLE=Extract From Tetrastigma hemsleyanum Leaf Alleviates Pseudomonas aeruginosa Lung Infection: Network Pharmacology Analysis and Experimental Evidence

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.587850

DOI=10.3389/fphar.2021.587850

ISSN=1663-9812

ABSTRACT=<p><italic>Tetrastigma hemsleyanum</italic> Diels &amp; Gilg (<italic>T. hemsleyanum</italic>) has attracted much attention due to its ability on pneumonia, bronchitis, and immune-related diseases, while its functional components and underlying mechanism of action on pneumonia have not been fully elucidated. Herein, we used a systematic network pharmacology approach to explore the action mechanism of <italic>T. hemsleyanum</italic> leaf in the treatment of pneumonia. In this study, the results of network pharmacology demonstrated that there were 34 active components and 80 drug–disease targets in <italic>T. hemsleyanum</italic> leaf, which were strongly in connection with signal transduction, inflammatory response, and the oxidation–reduction process. Subsequently, a mouse model of pneumonia induced by <italic>Pseudomonas aeruginosa</italic> (<italic>P. aeruginosa</italic>) was established to validate the predicted results of network pharmacology. In the animal experiments, aqueous extract of <italic>T. hemsleyanum</italic> leaf (EFT) significantly attenuated the histopathological changes of lung tissue in <italic>P. aeruginosa</italic>–induced mice and reduced the number of bacterial colonies in BALFs by 96.84% (<italic>p &lt;</italic> 0.01). Moreover, EFT treatment suppressed the increase of pro-inflammatory cytokines IL-17, IL-6, and TNF-α in lung tissues triggered by <italic>P. aeruginosa</italic>, which led to the increase of Th17 cells (<italic>p &lt;</italic> 0.05). High concentration of EFT treatment (2.0 g/kg) obviously increased the anti-inflammatory cytokine levels, accompanied by the enhancement of Treg proportion in a dose-dependent manner and a notable reversal of transcription factor RORγt expression. These findings demonstrated that network pharmacology was a useful tool for TCM research, and the anti-inflammatory effect of EFT was achieved by maintaining Th17/Treg immune homeostasis and thereby suppressing the inflammatory immune response.</p>