Exploring the mechanism of Yizhi Tongmai decoction in the treatment of vascular dementia through network pharmacology and molecular docking

Abstract

Background: Vascular dementia (VaD) is a degenerative cerebrovascular disease that leads to progressive decline of patients' cognitive ability and memory. Yizhi Tongmai (YZTM) decoction is an empirical prescription first formulated by Professor Guomin Si. Our previous experiments proved the effectiveness of this prescription in the treatment of VaD. In this study, we aimed to use network pharmacology and molecular docking technology to systematically explain the potential anti-VaD mechanism of YZTM.Methods: We identified the core compounds of YZTM and their potential targets through the TCMSP, BATMAN, and SwissTargetPrediction databases. Then, we identified the molecular targets of YZTM in VaD using the Online Mendelian Inheritance in Man and GeneCards databases. The common targets of YZTM and VaD were screened out, and then the pathways of these target genes were analyzed using the Database for Annotation, Visualization and Integrated Discovery v6.8. Molecular docking was used to verify the relationship between the core compounds and proteins.Results: Through network pharmacology analysis, we discovered that the 5 core compounds in YZTM exert an anti-VaD effect. The potential mechanism of YZTM anti-VaD may be through inhibiting the NLRP3 inflammasome, TNF signaling pathway, and toll-like receptor signaling pathways. Subsequently, key compounds were docked with related proteins in the NLRP3 inflammasome (NLRP3, ASC, caspase-1, interleukin-18, and interleukin-1 β) using molecular docking technology. The compounds were found to spontaneously bind to the proteins.Conclusions: YZTM may exert an anti-VaD effect through inhibition of the NLRP3 inflammasome.In addition, TNF signaling pathway and toll-like receptor signaling pathway may also be its underlying mechanism. The application of network pharmacology and molecular docking technology may provide a novel method for research of Chinese herbal medicine. YZTM may also provide a complementary treatment option for patients with VaD

Network Pharmacology and Experimental Validation to Reveal the Pharmacological Mechanisms of Liuwei Dihuang Decoction Against Intervertebral Disc Degeneration

“…And BC, CC, DC, EC, LAC, NC should be greater than or equal to the median value. 14 Functional Enrichment Analyses R software, a free software environment for statistical computing and graphics, was used to perform GO and KEGG functional enrichment analyses for the key targets.…”

“…13 With the development of computer technology and theory of system biology theory, network pharmacology is an emerging interdisciplinary subject, which has great advantages in interpreting the pharmacologic mechanisms of TCM with multiple components, targets and pathways, and is extremely commensurate with the holistic philosophy of TCM. [14][15][16] By network pharmacological analysis, Liu et al found 28 compounds and 421 targets in Huaihua-San formed the main pathways linked to ulcerative colitis, which revealed the mechanism of Huaihua-San against ulcerative colitis. 17 Similarly, with the help of network pharmacology, we predicted and verified the potential pharmacological mechanism of Bu-Yang herbs for postmenopausal osteoporosis via regulating the Wnt/β-catenin signaling pathway.…”

Exploring the Molecular Mechanism of Liuwei Dihuang Pills for Treating Diabetic Nephropathy by Combined Network Pharmacology and Molecular Docking

“…Because of the holism concept of TCM, Chinese medicinal formulas are usually treated diseases through several components and targets rather than a single one [ 13 ]. Network pharmacology can abstract the interaction relationship of drugs and targets into a network model and study them via a holistic perspective, consistent with the concept of holism in TCM [ 14 ]. In recent years, it has been recognized as an efficient method to study TCM.…”

Exploring the Molecular Mechanism of Liuwei Dihuang Pills for Treating Diabetic Nephropathy by Combined Network Pharmacology and Molecular Docking

“…Shi et al [10] also have found that LDP has a practical therapeutic effect on diabetic nephropathy. A meta-analysis including 14 RCT studies and 918 study participants has reported that LDP categorized formulas are safe and effective in treating DN proteinuria [11]. However, because of the characteristics of multi-compound and multi-target, exploring the underlying molecular mechanism of traditional Chinese medicine (TCM) through cellular or animal studies is relatively tricky [12] .…”

“…Because of the holism concept of TCM, Chinese medicinal formulas are usually treated diseases through several components and targets rather than a single one [13]. Network Pharmacology can abstract the interaction relationship of drugs and targets into a network model and study them via a holistic perspective, consistent with the concept of holism in TCM [14]. In recent years, it has been recognized as an e cient method to study TCM.…”