Study on the active components and mechanism of Suanzaoren decoction in improving cognitive impairment caused by sleep deprivation.

ETHNOPHARMACOLOGICAL RELEVANCE: Suanzaoren Decoction (SZRD) is a traditional and classic prescription for the treatment of insomnia, with a history of more than 1,000 years. It replenishes blood components, calms the nerves, reduces fever and irritability. It is commonly used in the clinical treatment of chronic fatigue syndrome, cardiac neurosis, and menopausal syndromes. Modern pharmacological studies have shown that it improves cognitive impairment; however, its mechanism of action remains unclear. AIM OF THE STUDY: This study preliminarily investigated the potential bioactive components and mechanism of SZRD in improving cognitive impairment by exploring network pharmacology, molecular docking, and conducting in vivo experiments. MATERIALS AND METHODS: The components of various Chinese herbs in SZRD and their disease-related targets were identified through network pharmacology and literature. Gene ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of intersection targets were performed using the relevant database. Next, the "Components-Targets-Pathways" (C-T-P) and "Protein-Protein interaction" networks were constructed using the enrichment analysis results to further identify potential pathways, bioactive components, and hub genes. At the same time, molecular docking was used to further distinguish the key bioactive components and genes of SZRD responsible for improving cognitive impairment. Finally, the potential mechanism of action was further analysed and verified using in vivo experiments. RESULTS: A total of 117 potential active components and 138 intersection targets were identified by network pharmacology screening. The key bioactive components, including calycosin, 5-Prenylbutein, licochalcone G, glypallichalcone, and ZINC189892, were identified by analysing the networks and molecular docking results. Hub genes included ACHE, CYP19A1, EGFR, ESR1, and ESR2. The oestrogen signalling pathway was the most important in the enrichment analysis. In vivo experiments further proved that SZRD could improve cognitive impairment by affecting the oestrogen signalling pathway and the expression of ACHE and CYP19A1. CONCLUSIONS: Network pharmacology and in vivo experiments demonstrate that SZRD improves cognitive impairment caused by sleep disturbance through estrogen receptor pathway, which provides a basis for its clinical application.

Cyanidin-3-O-glucoside inhibits the ß-catenin/MGMT pathway by upregulating miR-214-5p to reverse chemotherapy resistance in glioma cells.

Overcoming resistance to alkylating agents has important clinical significance in glioma. Cyanidin-3-O-glucoside (C3G) has a tumor-suppressive effect on tumor cells. However, whether it plays a role in temozolomide resistance in glioma is still unclear. We constructed a TMZ-resistant LN-18/TR glioma cell line, observed the effect of C3G on TMZ resistance in this cell line, and explored the role of miR-214-5p in chemoresistance. Results showed that ß-catenin and MGMT were significantly upregulated in LN-18/TR cells. C3G upregulated miR-214-5p and enhanced the cytotoxic effect of temozolomide on LN-18/TR cells. Contrarily, C3G downregulated ß-catenin and MGMT. Moreover, the miR-214-5p mimic downregulated ß-catenin and MGMT in LN-18/TR cells, whereas the miR-214-5p inhibitor had the opposite effect; the miR-214-5p inhibitor significantly blocked the C3G-induced downregulation of ß-catenin and MGMT. C3G or the miR-214-5p mimic enhanced temozolomide-induced apoptosis in LN-18/TR cells, whereas the miR-214-5p inhibitor blocked this effect. Furthermore, C3G or miR-214-5p agomir combined with TMZ significantly inhibited the growth of LN-18/TR tumors. Collectively, our research discovered the potential signaling mechanism associated with C3G-mediated suppression of TMZ resistance in LN-18/TR cells through miR-214-5p, which can facilitate the treatment of MGMT-induced resistance in glioma cells.

Activation of CNR1/PI3K/AKT Pathway by Tanshinone IIA Protects Hippocampal Neurons and Ameliorates Sleep Deprivation-Induced Cognitive Dysfunction in Rats.

Sleep deprivation is commonplace in modern society, Short periods of continuous sleep deprivation (SD) may negatively affect brain and behavioral function and may lead to vehicle accidents and medical errors. Tanshinone IIA (Tan IIA) is an important lipid-soluble component of Salvia miltiorrhiza, which could exert neuroprotective effects. The aim of this study was to investigate the mechanism of neuroprotective effect of Tan IIA on acute sleep deprivation-induced cognitive dysfunction in rats. Tan IIA ameliorated behavioral abnormalities in sleep deprived rats, enhanced behavioral performance in WMW and NOR experiments, increased hippocampal dendritic spine density, and attenuated atrophic loss of hippocampal neurons. Tan IIA enhanced the expression of CB1, PI3K, AKT, STAT3 in rat hippocampus and down-regulated the expression ratio of Bax to Bcl-2. These effects were inhibited by cannabinoid receptor 1 antagonist (AM251). In conclusion, Tan IIA can play a neuroprotective role by activating the CNR1/PI3K/AKT signaling pathway to antagonize apoptosis in the hippocampus and improve sleep deprivation-induced spatial recognition and learning memory dysfunction in rats. Our study suggests that Tan IIA may be a candidate for the prevention of sleep deprivation-induced dysfunction in spatial recognition and learning memory.

Tanshinone IIA suppresses the progression of lung adenocarcinoma through regulating CCNA2-CDK2 complex and AURKA/PLK1 pathway.

Lung adenocarcinoma (LUAD) belongs to a subgroup of non-small cell lung cancer (NSCLC) with an increasing incidence all over the world. Tanshinone IIA (TSA), an active compound of Salvia miltiorrhiza Bunge., has been found to have anti-tumor effects on many tumors, but its anti-LUAD effect and its mechanism have not been reported yet. In this study, bio-information analysis was applied to characterize the potential mechanism of TSA on LUA, biological experiments were used to verify the mechanisms involved. TCGA, Pubchem, SwissTargetPrediction, Venny2.1.0, STRING, DAVID, Cytoscape 3.7.2, Omicshare, GEPIA, RSCBPDB, Chem Draw, AutoDockTools, and PyMOL were utilized for analysis in the bio-information analysis and network pharmacology. Our experiments in vitro focused on the anti-LUAD effects and mechanisms of TSA on LUAD cells (A549 and NCI-H1975 cells) via MTT, plate cloning, Annexin V-FITC and PI dual staining, flow cytometry, and western blot assays. A total of 64 differentially expressed genes (DEGs) of TSA for treatment of LUAD were screened out. Gene ontology and pathway analysis revealed characteristic of the DEGs network. After GEPIA-based DEGs confirmation, 46 genes were considered having significant differences. Further, 10 key DEGs (BTK, HSD11B1, ADAM33, TNNC1, THRA, CCNA2, AURKA, MIF, PLK1, and SORD) were identified as the most likely relevant genes from overall survival analysis. Molecular Docking results showed that CCNA2, CDK2 and PLK1 had the lowest docking energy. MTT and plate cloning assays results showed that TSA inhibited the proliferation of LUAD cells in a concentration-dependent manner. Annexin V-FITC and PI dual staining and flow cytometry assays results told that TSA promoted the apoptosis of the two LUAD cells in different degrees, and induced cycle arrest in the G1/S phase. Western blot results showed that TSA significantly down-regulated the expression of CCNA2, CDK2, AURKA, PLK1, and p-ERK. In summary, TSA could suppress the progression of LUAD by inducing cell apoptosis and arresting cell cycle, and these were done by regulating CCNA2-CDK2 complex and AURKA/PLK1 pathway. These findings are the first to demonstrate the molecular mechanism of TSA in treatment of LUAD combination of network bio-information analysis and biological experiments in vitro.