Antipyretic effect and its mechanism of Tetrastigma hemsleyanum by network pharmacology and experimental verification
Objective To investigate the antipyretic mechanisms of Tetrastigma hemsleyanum based on network pharmacology and animal experiments. Methods GeneCards,DisGeNet,and other databases were used to screen the targets of T. hemsleyanum and fever,obtain the intersection targets of the two,and construct the active ingredient-target network. Then,STRING database and Cytoscape software were used to construct a shared target PPI network. GO and KEGG pathway enrichment analysis were performed for common targets using Metascape database. Finally,AutoDock software was used to perform molecular docking between the active ingredients of T. hemsleyanum and the core target protein,and the predicted results of network pharmacology were verified in vivo. Ip lipopolysaccharide induced fever model of mice,combined with water extract of T. hemsleyanum (2.5,12.5,25 g/kg) and aspirin were given ig,and then anal temperature of mice in each group was measured. The levels of fever-related cytokines (TNF-α,IL-6,IL-1β,and PGE2) in serum were detected by ELISA kit,and the relative expression of corresponding predicted targets in hypothalamus tissues of each group was detected by Western blotting. Results Network pharmacological results showed that T. hemsleyanum may act on 98 targets related to cancer pathways,AGE-RAGE signaling pathways in diabetes complications. Molecular docking results showed that emodion-1-O-β-D-glucopyranoside,procyanidin B1,and luteolin had strong binding activity and stable binding conformation with the three core target proteins HSP90AA1,NOS2 and NOS3. The animal experiments showed that compared with the model group,the body temperature and serum TNF-α,IL-6 and IL-1β of water extract of T. hemsleyanum 2.5,12.5,and 25 g/kg groups were significantly decreased (P<0.05). Western blotting detection showed that,the expression levels of HSP90AA1,NOS2,and NOS3 in T. hemsleyanum 2.5,12.5,and 25 g/kg water extract groups were down-regulated (P<0.05). Conclusion Antipyretic effect of T. hemsleyanum can reduce the expression of inflammation and febrile related cytokines. In addition,the antipyretic effect of T. hemsleyanum is related to the inhibition of the expression of HSP90AA1,NOS2 and NOS3 proteins.
T. hemsleyanumantipyreticnetwork pharmacologymolecular dockingemodion-1-O-β-D-glucopyranosideprocyanidin B1luteolin
NETL
NSTL
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