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Venenum Bufonis (VB), also called Chan Su in China, has been extensively used as a traditional Chinese medicine (TCM) for treating heart failure (HF) since ancient time. However, the active components and the potential anti-HF mechanism of VB remain unclear. In the current study, the major absorbed components and metabolites of VB after oral administration in rats were first collected from literatures. A total of 17 prototypes and 25 metabolites were gathered. Next, a feasible network-based pharmacological approach was developed and employed to explore the therapeutic mechanism of VB on HF based on the collected constituents. In total, 158 main targets were screened out and considered as effective players in ameliorating HF. Then, the VB components-main HF putative targets-main pathways network was established, clarifying the underlying biological process of VB on HF. More importantly, the main hubs were found to be highly enriched in adrenergic signalling in cardio-myocytes. After verified by molecular docking studies, four key targets (ATP1A1, GNAS, MAPK1 and PRKCA) and three potential active leading compounds (bufotalin, cinobufaginol and 19-oxo-bufalin) were identified, which may play critical roles in cardiac muscle contraction. This study demonstrated that the integrated strategy based on network pharmacology and molecular docking was helpful to uncover the synergistic mechanism of multiple constituents in TCM.
Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi), have gained approval for treating patients with castration-resistant prostate cancer (CRPC). Maternally expressed gene 3 (MEG3), a long non-coding RNA (lncRNA), plays a role in inhibiting tumorigenesis through regulating DNA repair genes. This study aimed to investigate the association between the anti-prostate cancer (PCa) effect of niraparib, a representative PARPi, and MEG3 expression, as well as explore the downstream pathway involved.
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