Abstract
Stroke is a complicated disease with an increasing incidence and a very high mortality rate. A classical Chinese herbal medicine, Dengzhan Shengmai (DZSM), has shown to have therapeutic effects on stroke; however, its chemical basis and molecular mechanism are still unclear. In this study, a systems biology approach was applicable to elucidate the underlying mechanism of action of DZSM on stroke. All the compounds were obtained from databases, and pendant-related targets were obtained from various data platforms, including the TCM Systematic Pharmacology (TCMSP) database, TCM Integrated Database (TCMIP), High Throughput Experimental Reference Database (HERB), Comparative Toxicogenomics Database (CTD), SwissTargetPredicition, and SymMap, The Human Gene Database (GENECARD) and Comparative Toxicogenomics Database (CTD) were used for stroke disease target data, followed by network pharmacology analysis to predict the potential effect of DZSM on stroke. Animal experiments were intended to validate the underlying mechanisms. A total of 846 chemical components were compiled for the targets of DZSM drug, and quercetin, kaempferol, and Wuweizisu C are the highest chemical components compiled from DZSM. Overlapping with 375 disease-specific targets and 149 core targets, the core targets include TNF, IL-6, ALB, and AKT1, which are shown to regulate the disease process from an anti-inflammatory perspective. 198 enrichment messages were obtained by KEGG enrichment analysis, and we believe that the role of the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, and IL-17 signaling pathway is more important. Based on rat experiments, we also demonstrated that DZSM could effectively modulate the inflammation level of brain infarct tissues and effectively alleviate behavioral characteristics. Grouped together, our study suggests that the combination of network pharmacology prediction and experimental validation can provide a useful tool to describe the molecular mechanisms of DZSM in Chinese medicine (TCM).
Highlights
Stroke is a syndrome of localized cerebral arterial vascular blockage, resulting in hypoxia and ischemia of brain tissue in the area of vascular innervation, causing corresponding neurological dysfunction, which is the main cause of longterm disability and reduced quality of life in later life [1, 2]
Screening of Active Ingredients. e High roughput Experimental Reference Database (HERB) database, Swiss database, TCM Systematic Pharmacology (TCMSP) database, Comparative Toxicogenomics Database (CTD) database, and SYMMAP database were utilized to predict the ingredients of Dengzhan Shengmai (DZSM)
Prediction of Drug-Related Targets. e TCMSP, HERB SWISSTARGET, CTD, and SYMMAP database were used to predict the targets of DZSM, and the targets were predicted in the Uniport online protein database (Uniprot), to find the corresponding standard gene name, so as to obtain the related target of active ingredients of DZSM
Summary
Stroke is a syndrome of localized cerebral arterial vascular blockage, resulting in hypoxia and ischemia of brain tissue in the area of vascular innervation, causing corresponding neurological dysfunction, which is the main cause of longterm disability and reduced quality of life in later life [1, 2]. It is generally believed that the inflammatory response is an important cause of Evidence-Based Complementary and Alternative Medicine neural remodeling, mainly including vascular regeneration, axonal sprouting, and synaptic remodeling [8,9,10,11], and inflammation levels can affect axon generation, while axonal sprouting and synaptic remodeling can promote the establishment of neural circuits and compensate for the innervation of damaged areas; regulation of inflammation levels is crucial to promote neural remodeling in stroke [12, 13]. Ginseng is the most commonly used Chinese patent medicine for the treatment of stroke, which consists of Radix et Rhizoma Ginseng, Radix et Rhizoma Ginseng, Radix et Rhizoma Macrocephala, and Radix et Rhizoma Wu Wei Zi and has the effect of benefiting Qi and nourishing Yin, invigorating blood, and strengthening the brain. It is utilized to treat the symptoms of stroke by removing blood stasis and with ginseng, maitong, and wu wei zi to form the famous formula sang wei sheng to benefit qi and nourish yin. Benefiting qi and nourishing yin means that when qi is healthy, blood moves and when yin is sufficient, the brain and kidney are combined, so that brain nerve function is normal and nerve function is improved and restored after stroke
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