Abstract
The role of traditional Chinese medicine Prunella vulagaris L in the treatment of tumors and inflammation has been widely confirmed. We found that some signaling pathways of Prunella vulgaris L action can also regulate diabetes and hypertension, so we decided to study the active ingredients, potential targets and signaling pathway of Prunrlla vulgaris L, and explore the “multi-target, multi-pathway” molecular mechanism of Prunella vulgaris L on diabetes mellitus complicated with hypertension(DH). Methods. Based on TCMSP(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) and CNKI(China National Knowledge Infrastructure), the components and action targets related to Prunella vulgaris L were screened. The OMIM(Online Mendelian Inheritance in Man) and GeneCards (The human gene database) were used to search for targets related to DH. The “gene - drug - disease” relationship map was drawn by Cytoscape_v3.7.2 plug-in. The target was amplified by the STRING platform, and the “protein - protein” interaction relationship (PPI) network of the interacting target was obtained by the STRING online analysis platform and the Cytoscape_v3.7.2 plug-in. Finally, GO enrichment analysis and KEGG pathway enrichment analysis were conducted on David and Metascape platform to study the co-acting targets. Results. 11 active components, 41 key targets and 16 significant signaling pathways were identified from Prunella vulgaris L. The main active components of Prunella vulgaris L against DH were quercetin and kaumferol, etc, and potential action targets were IL-6 and INS, etc and signaling pathways were AGE-RAGE signaling pathway, TNF signaling pathway, MAPK signaling pathway, PI3K-AKT signaling pathway, etc. It involves in biological processes such as cell proliferation, apoptosis and inflammatory response. Conclusions. The main molecular mechanism of Prunella vulgaris L against DH is that sterols and flavonoids play an active role by affecting TNF signaling pathway, AGE-RAGE signaling pathway, MAPK pathway, PI3K-Akt pathway related targets such as IL-6 and INS.
Highlights
The global prevalence of diabetes mellitus (The following abbreviations are diabetes) has continued to grow in recent years
About 70-80% of patients with diabetes eventually die from cardiovascular complications [2], hypertension is one of them, both were associated with insulin resistance.People with diabetes are twice the risk of hypertension as non-diabetic patients, and Journal of Diabetes Research epidemiological studies prove that hypertension is significantly higher in the diabetic population than in the general population [3],40% ~50% of patients with type 2 diabetes have hypertension and almost 100% when diabetes combined with extensive renal impairment
The 162 gene targets for the drug active ingredient were obtained through the UNIPROT database gene pairing.The disease targets were crossed between the GeneCards database and 281 gene targets were obtained from the OMIM database
Summary
The global prevalence of diabetes mellitus (The following abbreviations are diabetes) has continued to grow in recent years. According to the International Diabetes Alliance, the estimated number of diabetes patients worldwide in 2019 was 463 million, and is increasing year by year [1]. In the pathogenesis of Western medicine, diabetes is a metabolic disease characterized by hyperglycemia due to a deficiency in insulin secretion or insulin dysfunction. Continuous hyperglycemia and long-term metabolic disorders can lead to damage to systemic tissues and organs, especially the eye, kidney, cardiovascular and nervous system, and the cause of which has not been fully clarified. When diabetes mellitus complicated with hypertension, the incidence and severity of coronary heart disease (including myocardial infarction) increased significantly [4]
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