Mechanism of Chaihu Shugan Powder () for Treating Depression Based on Network Pharmacology.

OBJECTIVE: To analyze the effective components of Chinese medicine (CM) contained in Chaihu Shugan Powder (, CSP) in the treatment of depressive disorders and to predict its anti-depressant mechanism by network pharmacology. METHODS: Absorption, distribution, metabolism, excretion, and toxicity calculation method was used to screen the active components of CSP. Traditional Chinese Medicine System Pharmacological Database Analysis Platform and text mining tool (GoPuMed database) were used to predict and screen the active ingredients of CSP and anti-depressive targets. Through Genetic Association Database, Therapeutic Target Database, and PharmGkb database targets for depression were obtained. Cytoscape3.2.1 software was used to establish a network map of the active ingredients-targets of CSP, and to analyze gene function and metabolic pathways through Database for Annotation, Visualization and Integrated Discovery and the Omicshare database. RESULTS: The 121 active ingredients and 15 depression-related targets which were screened from the database can exert antidepressant effects by improving the neural plasticity, growth, transfer condition and gene expression of neuronal cell, and the raise of the expression of gap junction protein. The 15 targets passed 14 metabolic pathways, mainly involved in the regulation of neurotransmitters (5-hydroxytryptamine, dopamine and epinephrine), inflammatory mediator regulation of TRP channels, calcium signaling pathway, cyclic adenosine monophosphate signaling pathway and neuroactive ligand-receptor interaction and other signal channels to exert anti-depressant effects. CONCLUSION: This article reveals the possible mechanism of CSP in the treatment of depression through network pharmacology research, and lays a foundation for further target studies.

Effect of Circular ANRIL on the Inflammatory Response of Vascular Endothelial Cells in a Rat Model of Coronary Atherosclerosis.

BACKGROUND/AIMS: This study aims to investigate the role of circular antisense non-coding RNA at the INK4 locus (cANRIL) in the inflammatory response of vascular endothelial cells (ECs) in a rat model of coronary atherosclerosis (AS). A rat model of AS was established with rats that were injected with a large dose of vitamin D3 and fed a high-fat diet. METHODS: Sixty Wistar rats were randomly assigned into control, model, empty vector, over-expressed cANRIL and low-expressed cANRIL groups (12 rats in each group). Sixteen weeks later, the ultrastructure of their coronary arteries was observed via transmission electron microscopy. Rat serum lipid levels were analyzed using an automatic biochemical analyzer, and their atherogenic index (AI) values were calculated. Hematoxylin and eosin staining was used to observe the endothelial morphology of rats. Additionally, rat EC apoptosis was tested via a TUNEL assay. Enzyme-linked immunosorbent assays (ELISAs) were applied to measure serum levels of interleukin-1 (IL-1), IL-6, matrix metalloproteinase-9 (MMP-9) and C-reactive protein (CRP). The cANRIL, Bax, bcl-2 and caspase-3 mRNA expression levels were measured with a quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression levels of Bax, bcl-2 and caspase-3 were detected using immunohistochemistry. RESULTS: In the control group, ECs were closely arranged with normal structures, and there was no proliferation. In the model, empty vector and over-expressed cANRIL groups, some cells were not present, and atherosclerotic plaques and thrombi appeared. However, in the under-expressed cANRIL group, the cells had a normal structure. Compared with the model and empty vector groups, the levels of total cholesterol (CHOL), triglycerides (TGs), low density lipoprotein (LDL), IL-1, IL-6, MMP-9, CRP, cANRIL, Bax, and caspase-3, AI values, and rates of EC apoptosis decreased in the low-expressed cANRIL group, while HDL (high density lipoprotein) levels and mRNA and protein expression levels of bcl-2 were increased. The changes in expression levels in the over-expressed cANRIL group were the opposite of those in the low-expressed cANRIL group. CONCLUSIONS: Our study provides evidence that reduced cANRIL expression could prevent coronary AS by reducing vascular EC apoptosis and inflammatory factor expression.

MicroRNA-130a alleviates human coronary artery endothelial cell injury and inflammatory responses by targeting PTEN via activating PI3K/Akt/eNOS signaling pathway.

Our study aims to investigate the roles of microRNA-130a (miR-130a) in human coronary artery endothelial cells (HCAECs) injury and inflammatory responses by targeting PTEN through the PI3K/Akt/eNOS signaling pathway. HCAECs were treated with 1.0 mmol/L homocysteine (HCY) and assigned into eight groups: the blank group, the negative control (NC) group, the miR-130a mimics group, the miR-130a inhibitors group, the si-PTEN group, the Wortmannin group, the miR-130a inhibitors + si-PTEN group and the miR-130a mimics + Wortmannin group. Luciferase reporter gene assay was used to validate the relationship between miR-130a and PTEN. The expressions of miR-130a, PTEN and PI3K/Akt/eNOS signaling pathway-related proteins were detected by qRT-PCR assay and Western blotting. MTT assay and Hoechst 33258 staining were adopted to testify cell growth and apoptosis. The NO kit assay was used to detect the NO release. ELISA was conducted to measure serum cytokine levels. Luciferase reporter gene assay confirmed the target relationship between miR-130a and PTEN. Compared with the blank and NC groups, the miR-130a mimics and si-PTEN groups showed significant increases in the expressions of PI3K/Akt/eNOS signaling pathway-related proteins, cell viability and the NO release, while serum cytokine levels and cell apoptosis were decreased; by contrast, an opposite trend was observed in miR-130a inhibitors and Wortmannin groups. However, no significant difference was found in the miR-130a inhibitors + si-PTEN and miR-130a mimics + Wortmannin groups when compared with the blank group. These results indicate that miR-130a could alleviate HCAECs injury and inflammatory responses by down-regulating PTEN and activating PI3K/Akt/eNOS signaling pathway.