Mechanism of Lanlian Recipe in the inhibition of HIV based on network pharmacology and experiment

QIN Mingzhen; CHEN Lu; LIU Yu; LAN Mingsheng; LYU Jiannan; WU Wuwei

doi:10.13506/j.cnki.jpr.2023.12.004

Abstract：Objective The molecular mechanism of Lanlian Recipe in the inhibition of human immunodeficiency virus(HIV)was analyzed based on the network pharmacological method,providing a reference for the basic research and devel-opment of new drugs of anti-HIV.Methods The main chemical compositions of the components of Lanlian Recipe and the potential therapeutic targets were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The potential targets were introduced into UniProt for standardization after ADME screening.The HIV related targets were screened form Genecards,OMIM,TTD and DrugBank databases.Metascape platform was applied to ana-lyze the main biological processes and signal pathways of those HIV related targets.A"drug ingredients-targets-pathways"network and Protein-Protein Interaction Network(PPI)was constructed using Cytoscape 3.8.0 software and STRING data-base.The active ingredients of Lanlian Recipe were selected for molecular docking with the core targets through AutoDock Vina 1.2.3.The cytotoxicity to TZM-bl cell and the anti-HIV activity of Lanlian Recipe were determined in vitro.Results Our study showed that the main HIV-related active ingredients of Lanlian Recipe are quercetin,luteolin,kaempferol,baica-lein and the core targets are AKT1,TNF,CASP3,etc.The main signaling pathways of Lanlian Recipe that regulating HIV are PI3K-AKT,TNF and IL-17 pathway.The molecular docking showed that a good binding activity between the active ingredi-ents and core targets.The CC50 of Lanlian Recipe and Tangcao Tablets for control that inhibiting HIV pseudo virus were 3.16 and 2.01 mg·mL-1,respectively,and the IC50 are 17.10 and 94.42 μg·mL-1,respectively.These showed that Lanlian Recipe has a better anti-HIV activity than Tangcao Tablets(P<0.05).The result of quantitative real-time PCR revealed that Lan-lian Recipe can significantly increase the expression of IL-17.Conclusion Lanlian Recipe can inhibit the proliferation of HIV in TZM-bl cells,and the main mechanism probable to interfere with HIV by regulating IL-17 signaling pathway.