Network pharmacology and in vitro studies reveal the pharmacological effects and molecular mechanisms of Shenzhi Jiannao prescription against vascular dementia

Abstract

Background Shenzhi Jiannao (SZJN) prescription is a type of herbal formula adopted in the management of cognitive impairment and related disorders. However, its effects and related regulatory mechanisms on vascular dementia (VD) are elusive. Herein, network pharmacology prediction was employed to explore the pharmacological effects and molecular mechanisms of SZJN prescription on VD using network pharmacology prediction, and validated the results through in vitro experiments. Methods Through a search in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, chemical composition and targets for SZJN prescription were retrieved. The potential targets for VD were then obtained from the GeneCards and DisGeNET databases. The network was constructed that depicted the interactions between putative SZJN prescription and known therapeutic targets for VD using Cytoscape 3.7.1. Analysis of protein-protein interaction was achieved via STRING 11.0 software, followed by Gene Ontology (GO) functional enrichment and Kyoto Gene and Genome Encyclopedia (KEGG) pathway analyses. To validate the computer-predicted results, in vitro experiments based on an excitotoxic injury model were designed using glutamate-exposed PC12 cells, and treated with varying concentrations (low, 0.05; medium, 0.1 and high, 0.2 mg/mL) of SZJN prescription. Cell viability and cell death were detected using the IncuCyte imaging system. Moreover, the expression profiles of Caspase-3 were analyzed through qRT-PCR. Results Twenty-eight potentially active ingredients for SZJN prescription, including stigmasterol, beta-sitosterol, and kaempferol, plus 21 therapeutic targets for VD, including PTGS2, PTGS1, and PGR were revealed. The protein-protein interaction network was employed for the analysis of 20 target proteins, including CASP3, JUN, and AChE. The enrichment analysis demonstrated candidate targets of SZJN prescription were more frequently involved in neuroactive ligand-receptor interaction, calcium, apoptosis, and cholinergic synaptic signaling pathways. In vitro experiments revealed that SZJN prescription could significantly reverse glutamate-induced cell viability loss and cell death, and lower the levels of Caspase-3 mRNA in glutamate-induced PC12 cells. Conclusions Collectively, this study demonstrated that SZJN prescription exerted the effect of treating VD by regulating multi-targets and multi-channels with multi-components through the method of network pharmacology. Furthermore, in vitro results confirmed that SZJN prescription attenuated glutamate-induced neurotoxicity.

Analysis of Potential Mechanism of Herbal Formula Taohong Siwu Decoction against Vascular Dementia Based on Network Pharmacology and Molecular Docking

“…In this study, it was revealed that kaempferol, baicalein, beta-carotene, luteolin, quercetin, and beta-sitosterol in TSD might have potential therapeutic effects on the treatment of VaD based on network analysis. Kaempferol, mainly derived from Carthami Flos and Paeoniae Radix Alba , plays an important role in improving the damage of striatal neurons [ 21 ]. β -Sitosterol derived from Persicae Semen , Paeoniae Radix Alba , Carthami Flos , and Angelicae Sinensis Radi x is regarded to have a crucial role in potentially reducing neuron demyelination and blood lipids [ 21 ].…”

“…Kaempferol, mainly derived from Carthami Flos and Paeoniae Radix Alba , plays an important role in improving the damage of striatal neurons [ 21 ]. β -Sitosterol derived from Persicae Semen , Paeoniae Radix Alba , Carthami Flos , and Angelicae Sinensis Radi x is regarded to have a crucial role in potentially reducing neuron demyelination and blood lipids [ 21 ]. Luteolin, one of C arthami Flos ' major ingredients, is involved in the inflammatory response of VaD by inhibiting the expression of AP-1 and NF- κ B [ 22 ].…”

Mechanisms underlying the therapeutic effects of banxiaxiexin decoction in treating vascular dementia based on network pharmacology and molecular docking

“…CASP3 also emerges as a crucial player in dementia-related conditions. Shenzhiganao, an established prescription for dementia, signi cantly reduces CASP3 mRNA levels, particularly in glutamate-induced PC12 cells [21]. The molecular basis for VD amelioration by ligustrazine involves the inactivation of Bax/Bcl-2 and apoptotic CASP3 pathways [22].…”

Integrated Network Pharmacology and Proteomic Analyses of Targets and Mechanisms of Jianpi Tianjing Decoction in Treating Vascular Dementia

“…Tian et al successfully predicted 28 potentially active Shenzhi Jiannao prescription ingredients and 21 VD therapy targets. They found that the potential targets of these 28 active ingredients mainly involve neuroactive ligand-receptor interactions, calcium, apoptosis, and cholinergic synaptic signaling pathways [ 28 ]. Through network pharmacology analysis, Shi et al discovered that the five core compounds in Yizhi Tongmai decoction exert antiVD effects [ 29 ].…”