Network pharmacology and experimental evaluation strategies to decipher the underlying pharmacological mechanism of Traditional Chinese Medicine CFF-1 against prostate cancer.

Prostate cancer (PCa) is a common malignancy in elderly men. We have applied Traditional Chinese Medicine CFF-1 in clinical treatments for PCa for several years. Here, we aimed to identify the underlying mechanism of CFF-1 on PCa using network pharmacology and experimental validation. Active ingredients, potential targets of CFF-1 were acquired from the public databases. Subsequently, protein-protein interaction (PPI) and the herbs-active ingredients-target network was constructed. A prognostic model for PCa was also constructed based on key targets. In vitro experiments using PCa cell lines CWR22Rv1 and PC-3 were carried out to validate the potential mechanism of CFF-1 on PCa. A total of 112 bioactive compounds and 359 key targets were screened from public databases. PPI and herbs-active ingredients-target network analysis determined 12 genes as the main targets of CFF-1 on PCa. Molecular docking studies indicated that the primary active ingredients of CFF-1 possess strong binding affinity to the top five hub targets. DNMT3B, RXRB and HPRT1 were found to be involved in immune regulation of PCa. In vitro, CFF-1 was found to inhibit PCa cell proliferation, migration, invasion and induce apoptosis via PI3K-Akt, HIF-1, TNF, EGFR-TKI resistance and PD-1 checkpoint signaling pathways. This study comprehensively elucidates the underlying molecular mechanism of CFF-1 against PCa, offering a strong rationale for clinical application of CFF-1 in PCa treatment.

Dietary daidzein improved intestinal health of juvenile turbot in terms of intestinal mucosal barrier function and intestinal microbiota.

A 12-week feeding trial was conducted to investigate the effect of dietary daidzein on the intestinal mucosal barrier function and the intestinal microbiota profile of juvenile turbot (Scophthalmus maximus L.). Three isonitrogenous and isolipidic experimental diets were formulated to contain 0 (FM), 40 (D.40) and 400 (D.400) mg kg-1 daidzein, respectively. Fish fed D.400 had significantly lower growth performance than fish fed D.40. Dietary daidzein significantly increased the feed efficiency, while significantly decreased the feed intake. Daidzein supplementation increased the activity of total anti-oxidative capacity and the gene expression of anti-inflammatory cytokine transforming growth factor-ß1, Mucin-2 and tight junction proteins (Tricellulin, Zonula occludens-1 transcript variant 1, Zonula occludens-1 transcript variant 2 and Claudin-like and Occludin), and down-regulated the gene expression of pro-inflammatory cytokines interleukin-1ß and tumor necrosis factor-α in the intestine of turbot. Dietary daidzein increased intestinal microbial diversities, the abundance of several short chain fatty acids producers, and decreased the abundance of some potential pathogenic bacteria. However, D.400 had dual effects on lactic acid bacteria and increased the abundance of potential harmful bacterium Prevotella copri. Collectively, dietary daidzein at the levels of 40 and 400 mg kg-1 could enhance the intestinal mucosal barrier function and alter the intestinal microbiota of turbot. However, high dose of daidzein must be treated with caution for its unclear effects on intestinal microbiota of turbot in the present study.