Evaluation of the Mechanism of Action of Rosemary Volatile Oil in the Treatment of Alzheimer's Disease Using Gas Chromatography -mass Spectrometry Analysis and Network Pharmacology.

OBJECTIVE: This study aimed to investigate the active components and mechanism of action of rosemary volatile oil for treating Alzheimer's disease (AD) using network pharmacology. METHODS: We obtained the constituents of the rosemary volatile oil by searching Chinese herbal systemic pharmacological databases and analytical platforms and constructed the constituent-target networks by predicting and screening the action targets of the rosemary volatile oil constituents using SwissTargetPrediction, metaTarFisher, and Pubchem. We obtained the AD-related targets using the Genecards, OMIM, and DisGeNET databases and constructed the protein-protein interaction networks (PPI) using the STRING database in Venny 2.1.0 graph to identify the cross-targets by screening the core-acting targets. Cytoscape 3.8.2 software was used to construct a componenttarget- pathway network to screen the potential active components of the rosemary volatile oil for the treatment of AD and predict the mechanism of action of the rosemary volatile oil for the treatment of AD in combination with existing pharmacological studies. We performed a gene ontology (GO) biological process and a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the targets of the rosemary volatile oil for the treatment of AD using R language and molecular docking using Discovery Studio 4.0 software to validate their biological activities. RESULTS: A network constructed using gas chromatography-mass spectrometry (GC-MS) analysis identified 26 potentially active ingredients in the rosemary volatile oil. We retrieved a total of 10762 AD targets from Genecards and other databases. Our GO enrichment analysis yielded 39 entries (P < 0.05), including 14 entries for biological processes, five entries for cellular composition, and 20 entries for molecular function. A total of 14 entries (P < 0.05) were then enriched in the KEGG pathway that primarily involved the IL-17 signaling pathway and the AGE-RAGE pathway. CONCLUSION: The active components of rosemary volatile oil had good inhibition of the inflammatory response. This study provides a reference and guidance for the in-depth study on rosemary volatile oil for the treatment of AD.

Valerian essential oil for treating insomnia via the serotonergic synapse pathway.

Valerian volatile oil can be used in the treatment of insomnia; however, the active components and mechanisms of action are currently unclear. Therefore, we used transcriptome sequencing and weight coefficient network pharmacology to predict the effective components and mechanism of action of valerian volatile oil in an insomnia model induced by intraperitoneal injection of para-Chlorophenylalanine (PCPA) in SD rats. Valerian essential oil was given orally for treatment and the contents of 5-hydroxytryptamine receptor 1 A (5-HT1AR), γ-aminobutyric acid (GABA), cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA) in the hippocampus of rats in each group were detected by enzyme-linked immunosorbent assay (ELISA), western blot, Polymerase Chain Reaction (PCR), and immunohistochemistry. The results showed that after treatment with valerian essential oil, insomnia rats showed significantly prolonged sleep duration and alleviated insomnia-induced tension and anxiety. Regarding the mechanism of action, we believe that caryophyllene in valerian essential oil upregulates the 5-HT1AR receptor to improve the activity or affinity of the central transmitter 5-HT, increase the release of 5-HT, couple 5-HT with a G protein coupled receptor, convert adenosine triphosphate (ATP) into cAMP (catalyzed by ADCY5), and then directly regulate the downstream pathway. Following pathway activation, we propose that the core gene protein kinase PKA activates the serotonergic synapse signal pathway to increase the expression of 5-HT and GABA, thus improving insomnia symptoms and alleviating anxiety. This study provides a theoretical basis for the application of valerian volatile oil in health food.

The Mechanism Action of German Chamomile (Matricaria recutita L.) in the Treatment of Eczema: Based on Dose-Effect Weight Coefficient Network Pharmacology.

To determine the active ingredients in German chamomile volatile oil and the mechanism of action in the treatment of eczema, this study used two parameters (ingredient content and oil-water partition coefficient) and established a new network pharmacology method based on the dose-effect weight coefficient. Through the new network pharmacology method, we found that German chamomile volatile oil regulated T-cell lymphatic subpopulations to inhibit the Th17 cell differentiation signaling pathway. This resulted in a reduction of interleukin 17 (IL-17), thereby inhibiting the activation of the nuclear factor kappa beta (NF-κB) and MAPK pathways, decreasing the secretion of the pro-inflammatory factors (tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6)), and reducing inflammation. In this study, a new dose-effect relationship synergistic network pharmacology method was established to provide a new method for the screening of effective ingredients and pathways of drugs, and to provide a basis for the follow-up studies of German chamomile volatile oil in the treatment of eczema.

Mechanism of Action of Nicotiflorin from Tricyrtis maculata in the Treatment of Acute Myocardial Infarction: From Network Pharmacology to Experimental Pharmacology.

PURPOSE: Acute myocardial infarction (AMI) is a cardiovascular disease with a high fatality rate. In this study, we combined network pharmacology and experimental pharmacology and discovered the potential mechanism of action and the active ingredients of the lily, Tricyrtis maculata was discovered. The monomer compound with stronger activity was discovered through in vitro cell experiments. METHODS: Forty known compounds were isolated from T. maculata. Using TCMSP, Swiss Target Prediction, metaTarFisher, GeneCards and OMIM databases, targets of drug compositions and AMI-related genes were obtained, and the differential expression genes between AMI and normal tissues were extracted through the GEO database. Then, through an online mapping tool, the intersection genes were obtained to predict the possible effective components of T. maculata that can be used to treat AMI. The top five targets were selected for molecular docking via the protein-protein interaction (PPI) network to verify the binding activity between key compounds and target proteins. GO and KEGG enrichment analyses of the intersection genes were carried out with the program R to further screen key genes and effective compositions. On this basis, the compound with more optimal activity was screened and validated in vitro. RESULTS: In this study, 40 known monomer components were selected, and 1112 predicted genes, 1655 disease genes, 1425 differentially expressed genes, 1206 GO functions and 127 KEGG pathways were obtained. The results of molecular docking showed that the binding of MMP9 with drug components is stable. Through the comprehensive research of network pharmacology and experimental pharmacology, it was shown that T. maculata intervenes in the process of AMI through multicomponent, multitarget, and multichannel synergistic effects. It is speculated that the anti-AMI effect may be related to the regulation of the Akt/FoxO/BCl signaling pathway. Cellular experiments showed that nicotiflorin has satisfactory anti-inflammatory activity and endothelial protection and can reduce the release of nitric oxide (NO), an inflammatory medium after endothelial cell damage. CONCLUSION: This study reveals the therapeutic effect and relative mechanism of extract of T. maculata extract on AMI. Analysis revealed that nicotiflorin from T. maculata is a compound with satisfactory anti-inflammatory activity and endothelial protection, which provides a new direction and treatment basis for further experimental exploration and clinical treatment.

The Mechanism of Lavender Essential Oil in the Treatment of Acute Colitis Based on "Quantity-Effect" Weight Coefficient Network Pharmacology.

This study aimed to introduce a new weight coefficient combined with network pharmacology to predict the potential active components, action targets, and signal pathways of lavender essential oil and to investigate the therapeutic effect of lavender essential oil on colitis through animal experiments. The component targets of lavender essential oil were mined from the Pubchem and SwissTargetPrediction databases, and the relative content of lavender essential oil was compared with OB (oral bioavailability) to establish a "quantity-effect" weight coefficient. Online databases such as GeneCards and String were used to construct a "lavender essential oil compound target disease target" network to extract the key targets of core compounds acting on diseases. The clusterProfiler package in R language programming of Rstudio software was used to analyze the enrichment of the related targets by Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG), and the enriched pathways were reordered according to the "quantity-effect" weight coefficient of the targets they participated in. Following up on the findings, the pharmacodynamic test showed that, after injecting lavender essential oil into mice, the levels of inflammatory cytokines including EGFR, TNF-α, and IFN-γ in serum and colon tissue decreased, and lavender essential oil could mediate Th17 cell differentiation by reducing dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) colonic mucosal damage. The results indicated that lavender essential oil can alleviate DSS-induced colonic mucosal injury in ulcerative Colitis mice. Based on the network pharmacology of the "quantity-effect" weight coefficient, this study indicated that lavender essential oil can regulate the level of inflammatory factors, inhibit inflammatory reactions through a multicomponent and multitarget strategy, and ultimately alleviate the colonic mucosal injury of UC mice. Through the weight coefficient network pharmacology mining, it was concluded that the Th17 cell differentiation, PI3K-Akt signaling pathway, and Th1 and Th2 cell differentiation of lavender essential oil in the treatment of UC may be the key pathway for the treatment of the disease. Through the establishment of a weight coefficient combined with network pharmacology and the combination of dose and effect, it shows that network pharmacology may provide a better basis for the treatment of disease mechanism.

Mechanism of allergic rhinitis treated by Centipeda minima from different geographic areas.

CONTEXT: The coriander plant Centipeda minima (L.) A. Braun et Aschers (Compositae) is used for the treatment of allergic rhinitis. OBJECTIVE: Analyze the difference of the C. minima volatile oil from 7 geographic areas and its therapeutic effect on allergic rhinitis. MATERIALS AND METHODS: The volatile oils from different geographic areas were extracted and analyzed, the protein and biological pathway for the treatment of allergic rhinitis were predicted by network pharmacology. Established three groups of Sprague-Dawley rat allergic rhinitis models (n = 10). The treatment group was given 100 µL/nostril of 0.1% C. minima volatile oil, the blank and model groups were given the same amount of normal saline. After 15 days, serum inflammatory factors were detected by ELISA. Nasal mucosa tissues were examined by hematoxylineosin staining and immunuhistrochemistry. RESULTS: There are differences in the content of volatile oil in the seven geographic areas. Experiments showed that the concentration of TNF-α in the serum of the administration group decreased from 63.66 ± 2.06 to 51.01 ± 4.10 (pg/mL), IL-4 decreased from 41.90 ± 3.90 to 28.68 ± 3.39 (pg/mL), IgE decreased from 22.18 ± 1.40 to 17.59 ± 1.60 (pg/mL), IL-2 increased from 314.14 ± 10.32 to 355.90 ± 10.01(pg/mL). Immunohistochemistry showed that compared with the model group, the PTGS2 and MAPK3 proteins in the administration group were significantly reduced. DISCUSSION AND CONCLUSIONS: C. minima volatile oil is a multi-target and multi-pathway in the treatment of allergic rhinitis, which provides a new research basis and reference for the treatment of allergic rhinitis.

Action mechanism of Roman chamomile in the treatment of anxiety disorder based on network pharmacology.

Anxiety disorder is a common psychiatric disease. Roman chamomile as medicine or tea has long been used as a mild tranquilizer to reduce anxiety, but the mechanism is unclear. This research is based on network pharmacology combined with database mining to find the ingredients, action pathways and key targets of Roman chamomile for the treatment of anxiety. About 126 common targets related to chamomile and anxiety were obtained, and these targets were involved in 56 KEGG pathways. GEO screened LRRK2 as a key protein, and molecular docking showed that the protein could stably bind to drug components. Roman chamomile has the characteristics of multi-target and multi-pathway in the treatment of anxiety disorder. Its possible mechanism is to intervene anxiety disorder in the process of disease development, such as neuroactive ligand-receptor interaction, serotonin synapse, and cAMP signaling pathway. LRRK2 may be an important gene for Roman chamomile in the treatment of anxiety disorder. PRACTICAL APPLICATIONS: Roman chamomile is well known for its use in medicine and tea making. It contains many nutrients, which can relieve people's anxiety, help sleep, antibacterial and anti-inflammatory. In this article, through network pharmacology combined with Gene Expression Omnibus data mining and molecular docking, the target and mechanism of Roman chamomile in the treatment of anxiety were discussed, and its efficacy was verified by model animals, which not only clarified its mechanism at the systematic level, but also proved to be effective at the biological level. It provides a reference for the further development and utilization of Roman chamomile.

A Study on the Mechanism of Lavender in the Treatment of Insomnia Based on Network Pharmacology.

AIMS AND OBJECTIVE: The common disease of insomnia has complex and diverse clinical manifestations. Lavender represents an effective treatment of insomnia, but the molecular mechanism underlying the effectiveness of this treatment is not clear. The purpose of this study is to investigate the active components, target proteins and molecular pathways of lavender in the treatment of insomnia, thus explaining its possible mechanism. MATERIALS AND METHODS: Firstly, 54 active components of lavender were identified by gas chromatography-mass spectrometry (GC-MS). The target protein of lavender was predicted by the Traditional Chinese Medicine System Pharmacological Database and Analysis Platform and the SwissTargetPredicating tool, and the target protein of insomnia was predicted by the DisGeNET and DrugBank databases. Then, the "component-target-disease" network diagram was constructed using the Cytoscape 3.7.1 software. KEGG and GO enrichments were analyzed using the R statistical language. Finally, the key target proteins were verified by collecting and verifying the target protein GEO data using the Discovery Studio 3.5 molecular docking verification software. RESULTS: 906 target proteins of lavender were predicted by the Traditional Chinese Medicine System Pharmacological Database and Analysis Platform and the SwissTargetPredicating tool, and 182 insomnia target proteins were predicted by the DisGeNET and DrugBank databases. The results of GO enrichment analysis showed that it included the reaction process of ammonium ion, the regulation of the membrane potential and the secretion of catecholamine, while the results of KEGG enrichment included the calcium signaling pathway, serotonin synapse, morphine addiction and many more. Finally, using the Discovery Studio3.5 molecular docking verification software, it was verified that the key target proteins are ADRB1 and HLA-DRB1. CONCLUSION: The components in the lavender essential oil include the Ethyl 2-(5-methyl-5-vinyltetrahydrofuran- 2-yl)propan-2-ylcarbonate (0.774); 5-Oxatricyclo[8.2.0.04,6]dodecane, 4,12,12-trimethyl- 9-methylene-, (1R,4R,6R,10S)-(0.147); P-Cymen-7-ol (0.063); .alpha-Humulenem (0.317); Acetic acid, hexyl ester (1.374); etc. The role lavender plays in the treatment of insomnia might be accomplished through the regulation of the key targets ADRB1 and HLA-DRB1.