ABSTRACT
Aim To explore the effects of Zhishi Xiebai Guizhi Decoction (ZXGD) in the treatment of myocardial infarction (MI) using the network pharmacology method and verifying by in vivo experiments and to reveal the underlying mechanism. Methods The chemical components of ZXGD and related targets were retrieved from the TCMSP database. The targets of MI were searched from the GeneCards, OMIM and DisGeNET databases, with the keywords " myocardial infarction" and "MI", and removing duplicates. The intersection of ZXGD and MI targets were obtained, and a protein-protein interaction (PPI) network based on the intersection of active ingredients and disease targets was constructed. The DAVID database was used to conduct GO and KEGG pathway enrichment analysis on the intersection targets. Combined with STRING database and Cytoscape 3.7.2 software, the intersection targets were visualized as a " medicine-component-target-disease" network. The MI mouse model was established by ligation of the left anterior descending coronary artery of the heart. ZXGD was given once a day for 14 days. The cardioprotective effects of ZXGD were examined by ultrasound cardiogram and Western blot. Results The results of network pharmacology analysis showed that the pharmacological components of ZXGD such as quercetin, naringenin, β-sitosterol, and luteolin maybe work on the targets like TNF-α, IL-1β, IL-6, VEGFA, and IL-10. Animal experiments found that compared with the model group, ZXGD significantly increased the left ventricular cardiac function, outflow tract blood flow, and other ultrasound indexes of the mice (P < 0.05). Moreover, the expression levels of IL-1β, TNF-α and IL-6 in myocardial infarction tissue were significantly down-regulated by ZXGD (P < 0.05), while the expression level of IL-10 was significantly up-regulated (P < 0.05). Conclusion ZXGD protects against MI and improves heart function by regulating inflammatory factors including TNF-α, IL-1β, IL-6, and IL-10.
ABSTRACT
Aim To evaluate and compare the toxicity of psoralen on two-dimensional(2D)and three-dimensional(3D)cultured human hepatocyte HepG2 models. Methods The 3D cell model of HepG2 cells was constructed by low adsorption U-shaped bottom porous plate method. After treated with psoralen for 24 hours, the cell viabilities of 2D and 3D HepG2 cells were detected by CCK-8 assay, LDH leakage was detected by kit, and the mitochondrial membrane potential was detected by TMRM staining. The effect of psoralen on the mRNA of mitochondrial fusion-fission proteins DRP1, Mfn-2 and OPA1 was detected by Q-PCR. Results 3D model maintained a high level of albumin and urea secretion for a long time. And the expression levels of CYP1A2, CYP2E1, CYP3A4 and UGT1A1 in 3D model were higher than those in 2D model. In 3D model lower concentrations of psoralen showed a significant decrease in cell viability, a significant increase in LDH leakage, and a decrease in mitochondrial membrane potential. Q-PCR results showed that psoralen induced a marked increase in the expression of mitochondrial fission protein DRP1, while a significant decrease in mitochondrial fusion protein OPA1. Conclusions A 3D HepG2 cell model is successfully constructed and applied to the evaluation of psoralen hepatotoxicity; the 3D cell culture model is more sensitive to psoralen toxicity, and mitochondria may play a key role in psoralen-induced cell damage.