Systems Pharmacology-Based Strategy to Investigate Pharmacological Mechanisms of Total Flavonoids in Dracocephalum moldavica on Chronic Heart Failure

Abstract

Heart failure (HF) is a clinical syndrome of cardiac insufficiency caused by abnormalities in cardiac structure and function that arise for various reasons, and it is the final stage of most cardiovascular diseases’ progression. Total flavonoid extract from Dracocephalum moldavica L. (TFDM) has many pharmacological and biological roles, such as cardioprotective, neuroprotective, anti-atherogenic, antihypertensive, anti-diabetic, anti-inflammatory, antioxidant, etc. However, its effect on HF and its molecular mechanism are still unclear. In this study, we used systems pharmacology and an animal model of HF to investigate the cardioprotective effect of TFDM and its molecular mechanism. Eleven compounds in TFDM were obtained from the literature, and 114 overlapping genes related to TFDM and HF were collected from several databases. A PPI network and C-T network were established, and GO enrichment analysis and KEGG pathway analysis were performed. The top targets from the PPI network and C-T network were validated using molecular docking. The pharmacological activity was investigated in an HFpEF (heart failure with preserved ejection fraction) mouse model. This study shows that TFDM has a protective effect on HFpEF, and its protective mechanism may be related to the regulation of proinflammatory cytokines, apoptosis-related genes, fibrosis-related genes, etc. Collectively, this study offers new insights for researchers to understand the protective effect and mechanism of TFDM against HFpEF using a network pharmacology method and a murine model of HFpEF, which suggest that TFDM is a promising therapy for HFpEF in the clinic.

Evaluation of the Cytotoxic, Antioxidative and Antimicrobial Effects of Dracocephalum moldavica L. Cultivars

“…The chemical compositions of the three cultivars were dominated by the presence of flavonoids and phenolic acids. Almost all these compounds were previously identified in the composition of the species [ 6 , 11 , 12 , 13 , 14 , 22 , 25 , 49 , 53 ]. The novelty of the present study consists in the identification and quantification of ellagic, salycilic, and carnosic acids, together with naringenin and vitexin, which, to the best of our knowledge, are reported for the first time in this study.…”

“…Among flavonoids, tilianin is an interesting glycoside with important biological properties that was firstly isolated from this species [ 15 , 16 , 17 ]. Both classes of compounds are correlated to the biological activities of the species, such as its antioxidant [ 1 , 6 , 11 , 12 , 13 , 18 , 19 , 20 ], antimicrobial [ 1 , 18 , 21 , 22 ], and cardioprotective [ 15 , 23 , 24 , 25 , 26 , 27 ] effects, which are the most studied ones, together with its anti-inflammatory [ 28 , 29 ], neuroprotective [ 16 , 30 ], sedative [ 31 ], cytotoxic [ 14 , 32 ], and antidepressant [ 33 ] effects, which are lesser known. The antimicrobial potential of the species was attributed to its essential oils, linked to its antioxidant capacity and demonstrated against Staphylococcus aureus , Escherichia coli , Salmonella Typhimurium , and Listeria monocytogenes [ 1 , 18 ].…”

Exploring the effect and mechanism of Aloin A against cancer cachexia-induced muscle atrophy via network pharmacology, molecular docking, molecular dynamics and experimental validation

“…To validate the network pharmacology results and better understand protein-ligand interactions, we applied molecular docking and molecular dynamics (MD) simulation. Molecular docking is a structure-based method that enables the identification of novel compounds of therapeutic targets by predicting ligand–target interactions at a molecular level [ 52 , 53 ]. The more negative the binding energy, the more stable the binding of the compound to the target [ 54 ].…”