ABSTRACT
Objective:To investigate the potential mechanism of Shenfu injection in regulating stress response via the neuro-endocrine-immune system by network pharmacology and molecular docking. Methods:The main active ingredients and related targets of Shenfu injection were screened using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform.PharmMapper, Swiss Target Prediction platform and Uniprot database were used to predict the target and unify the gene names.GeneCards, OMIM, TTD, CTD, Drugbank, Disgenet and Pharmgkb databases were searched to screen the related targets regulated by stress responses.Venny 2.1 tool was used to obtain the potential effect targets of the intersection between Shenfu injection and stress response regulation, and the STRING database was imported to construct the interaction PPI network and screen the key targets.Potential effect targets were uploaded to Metascape database online analysis for study on the mechanism through GO and KEGG enrichment analysis.Autoduck and Pymol were used for molecular docking and visualization.Results:Forty-three main active ingredients and 257 related targets for Shenfu injection were obtained by component screening and target prediction.A total of 4 811 targets related to stress response regulation were retrieved from the database, 188 potential effect targets were obtained by intersection with Shenfu injection component-related targets, and 14 key targets were obtained by PPI network screening.Eighteen samples were screened by GO enrichment analysis, which mainly involved the circulatory system and humoral regulation, responses to external stimuli and trauma, MAPK cascade reaction, postsynaptic membrane, receptor complex and ion channel complex and neurotransmitter receptor activity, etc.KEGG enrichment analysis showed 20 highly correlated pathways, mainly covering neuroactive ligand-receptor interaction, calcium signaling pathway, adrenergic signaling, steroid hormone biosynthesis, IL-17, TNF, MAPK, cGMP-PKG, PI3K-Akt, NF-κB, Toll-like receptor signaling pathway and cell apoptosis, etc.The results of molecular docking indicated that the main active components had good binding force with the key target.Conclusions:The components of Shenfu injection such as kaempferol, β-sitosterol, Demethyldelavaine, Stigmasterol, ginsenoside, Carnosifloside, hypaconitine may act on targets such as AKT1, TNF, IL1B, PTGS2, HSP90AA1, MAPK1, NFKBIA, NR3C1 and ADRB2 and regulate the stress response through the mechanisms such as regulation of the functional state of the neuro-endocrino-immune system, inhibition of inflammatory responses, anti-oxidative stress and reduction of cell apoptosis.
ABSTRACT
Parkinson’s disease (PD) is a chronic neurological disorder of the nervoussystem, initiated by lessened production of dopamine (DA) in the substantia nigra, itaffects circa 50 percent more men than women. Theories reveal that age, genetic andenvironmental factors are involved in PD etiology but age seems to be the mostprominent risk factor. Monoamine oxidase B (MAO-B) play prominent role in theoxidative deamination of DA in the striatum. Inhibition of MAO-B in the brain maydecrease the exhaustion of DA stores and increase endogenous DA level. Glide-XPdocking, Quantum-mechanics Polarized Ligand Docking (QPLD), pharmacokineticstudies and biological activity prediction studies were utilized to explain the bindingmode, molecular interaction, inhibitory potential and pharmacokinetic properties ofTraditional Chinese Medicine (TCM) compounds on MAO-B and compared to standarddrugs used for treatment of PD, selegiline and rasagiline. Molecular docking resultsshowed Rutaecarpine and Chrysophanol to have relatively better inhibitory activitiesthan selegiline and rasagiline. Pharmacokinetic studies revealed that Rutaecarpine andChrysophanol show comparative result with selegiline and rasagiline. Also,Rutaecarpine and Chrysophanol PASS prediction for their monoamine inhibitoryactivity showed greater Pa than Pi value. Our results have shown that Rutaecarpine andChrysophanol can be a better therapeutic candidate in the treatment of PD.
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Objective:The interaction between lobetyolin and bovine serumal bumin（bovine serum albumin，BSA）. Method:By the steady-state fluorescence analysis method，the molecular-docking，ultraviolet absorption spectrum and fluorescence quenching were used to calculate quenching constant and binding constant，the number of sites，the position，the force and the distance of lobetyolin-BSA system. In addition， the effect of metalionson quenching constant of the lobetyolin-BSA system was studied. Result:The quenching constant was 1.25×104 L·mol-1（37 ℃），the binding constant was 2.95×104 L·mol-1（37 ℃），and the number of sites was 1 and bound with site 1 in ⅡA of BSA， thermodynamic meters were ΔH=-19.374 kJ·mol-1，ΔS=23.1 J·mol-1·K-1， the interaction distance was 3.2 nm. Meta lions could accelerate the quenching. Conclusion:By the steady-state fluorescence technique，molecular-docking and ultraviolet absorption spectrum，the quenching mechanism of Lobetyolin-BSA is quiescent quenching，and the interactive force is electro static force. The Lobetyolin-BSA can be well combined. At the same time，it also shows that the molecular docking results are similar to the experimental results obtained by steady-state fluorescence analysis.