BackgroundHeart failure (HF) and diabetes mellitus (DM) are life-threatening diseases. However, existing clinical drugs to treat HF complicated with DM are relatively limited. In this study, we performed a viable bioinformatics strategy combining network pharmacology and molecular docking to identify potential anti-HF and -DM targets and therapeutic mechanisms of calycosin, a functional phytoestrogen.MethodsWeb-based databases were used to collect candidate genes/targets of calycosin and HF/DM and then identify the hub bio-targets of calycosin against HF/DM. Using the online-available database, all functional processes and signaling pathways of calycosin against HF/DM were screened and identified before further visualization.ResultsAll potential bio-targets of calycosin and HF/DM were collected, and 20 hub targets of calycosin against HF/DM were identified. Interestingly, molecular docking findings indicated that mitogen-activated protein kinase-1 (MAPK1), β-arrestin 1 (ARRB1), and homologue-1 (ABL1) may be potent pharmacological targets of calycosin against HF/DM. In addition, all primary molecular functions of calycosin against HF/DM were identified, including regulating protein binding, ubiquitination, and the metabolic process. Furthermore, the top molecular pathways of calycosin against HF/DM were revealed, including cardiomyocyte and chemokine signaling pathways.ConclusionOur bioinformatics analysis uncovered the network targets and therapeutic mechanisms of calycosin against HF/DM. For the first time, the current in silico findings revealed that the identified hub targets may be used to screen and treat HF/DM.

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Exposure to arsenic (As), an inorganic poison, may lead to skin lesions, including dermatitis. Vitamin A (VA), a fat-soluble vitamin essential for mucous membrane integrity, plays a key role in skin protection. Although the beneficial actions of VA are known, the anti-As-related dermatitis effects of VA action remain unclear. Hence, in this study, we aimed to interpret and identify the core target genes and therapeutic mechanisms of VA action in the treatment of As-related dermatitis through integrated in silico approaches of network pharmacology and molecular docking. We integrated the key VA-biological target-signaling pathway-As-related dermatitis networks for identifying core drug targets and interaction pathways associated with VA action. The network pharmacology data indicated that VA may possess potential activity for treating As-related dermatitis through the effective regulation of core target genes. An enrichment analysis in biological processes further revealed multiple immunoregulation-associated functions, including interferon-gamma production and negative regulation of T-cell activation and production of molecular mediator of immune response. An enrichment analysis in molecular pathways mainly uncovered multiple biological signaling, including natural killer cell mediated cytotoxicity, autophagy, apoptosis, necroptosis, platelet activation involved in cell fate, and immunity regulations. Molecular docking study was used to identify docked well core target proteins with VA, including Jun, tumor protein p53 (TP53), mitogen-activated protein kinase-3 (MAPK3), MAPK1, and MAPK14. In conclusion, the potential use of VA may suppress the inflammatory stress and enhance the immunity against As-related dermatitis. In the future, VA might be useful in the treatment of dermatitis associated with As through multi-targets and multi-pathways in clinical practice.