我们研究了ZiziphoraclinopodioidesLam的作用机制。(ZCL)对动脉粥样硬化(AS)的网络药理学和体外验证。我们收集了ZCL的活性成分,并预测了它们在AS中的作用靶点。我们构建了蛋白质-蛋白质相互作用,复合靶,和目标-化合物-途径网络,并进行GO和KEGG分析。利用Autodock和Pymol软件构建活性成分与关键靶标的分子对接。用qRT-PCR进行验证,ELISA,和Westernblot。我们获得了80个组分的ZCL。网络分析确定了14个成分和37个基因与AS有关。然后,PPI网络中的10个关键节点被确定为ZCL的关键目标,因为它们在网络拓扑中的重要性。8种成分的结合能(西纳糖苷,α-Spinasterol,linarin,aempferide,Acacetin,Genkwanin,Chyrin,和Apiin)对4个目标(MMP9,TP53,AKT1,SRC)很强,<-1kJ/mol。此外,14种成分中的13种是黄酮类化合物,因此是Ziziphora的总黄酮。(ZCF)用于体外验证。我们发现ZCF降低eNOS,P22phox,gp91phox,和PCSK9在mRNA和蛋白质水平,以及IL-1β的水平,TNF-α,和IL-6蛋白的体外表达(P<0.05)。我们成功地预测了活性成分,目标,ZCL在网络药理学治疗AS中的作用机制。我们证实ZCF可能通过调节氧化应激在AS中发挥作用,脂质代谢,和通过Cynaroside的炎症反应,linarin,aempferide,Acacetin,Genkwanin,Chyrin,还有Apiin.
We investigated the mechanisms underlying the effects of Ziziphora clinopodioides Lam. (ZCL) on atherosclerosis (AS) using network pharmacology and in vitro validation.We collected the active components of ZCL and predicted their targets in AS. We constructed the protein-protein interaction, compound-target, and target-compound-pathway networks, and performed GO and KEGG analyses. Molecular docking of the active components and key targets was constructed with Autodock and Pymol software. Validation was performed with qRT-PCR, ELISA, and Western blot.We obtained 80 components of ZCL. The network analysis identified that 14 components and 37 genes were involved in AS. Then, 10 key nodes in the PPI network were identified as the key targets of ZCL because of their importance in network topology. The binding energy of 8 components (
Cynaroside, α-Spinasterol, Linarin, Kaempferide, Acacetin, Genkwanin, Chrysin, and Apiin) to 4 targets (MMP9, TP53, AKT1, SRC) was strong and <-1 kJ/mol. In addition, 13 of the 14 components were flavonoids and thus total flavonoids of Ziziphora clinopodioides Lam. (ZCF) were used for in vitro validation. We found that ZCF reduced eNOS, P22phox, gp91phox, and PCSK9 at mRNA and protein levels, as well as the levels of IL-1β, TNF-α, and IL-6 proteins in vitro (P < 0.05).We successfully predicted the active components, targets, and mechanisms of ZCL in treating AS using network pharmacology. We confirmed that ZCF may play a role in AS by modulating oxidative stress, lipid metabolism, and inflammatory response via
Cynaroside, Linarin, Kaempferide, Acacetin, Genkwanin, Chrysin, and Apiin.