Brahmi (Bacopa monnieri) plant preparation facilitates to enhance the activities of dendritic cells to control non-small cell lung cancer (NSCLC)
摘要
Brahmi (Bacopa monnieri) plant preparation (BPP) has been recognizedfor its immunomodulatory capabilities, but its molecular and epigenetic effects onimmune cells in non-small cell lung cancer (NSCLC) remain unknown.
ObjectiveThisstudy investigated the way BPP influenced the molecular phenotype and functionalprofile of monocyte-derived dendritic cells (DCs) derived from an NSCLC patient anda healthy donor.
ResultBPP treatment enhanced DC maturation, as demonstrated byelevated levels of CD1d and co-stimulatory molecules (CD80/CD86), and conditionedsupernatants that efficiently activated autologous T cells. BPP increased proinflammatorysignaling molecules STAT1, STAT2, STAT4, and total NF-κB, whiledecreasing STAT3, STAT5, STAT6, and the DNA-repair protein DNAPKcs.Transcriptional analysis indicated a Th1-oriented immune program, characterized bythe up-regulation of TBX21, IFNG, and TP53, alongside the down-regulation ofGATA3, FOXP3, RORC, IL10, and MYC. Chromatin profiling revealed an enrichmentof H3K4me3 and H3K14ac, alongside p53 recruitment at the IFNG/TBX21 loci,accompanied by diminished levels of H3K27me3, HDAC2, and reduced promoteroccupancy by c-Myc and NF-κB. BPP enhanced the secretion of IFN-γ, IL-2, and TNF-α while diminishing IL-4, IL-10, and IL-17, establishing a pro-inflammatoryenvironment indicative of Th1-type polarization. Co-culture experiments validatedincreased cytotoxic T-cell activity against A549 cells (NSCLC cells), assessed throughLDH release and statistically confirmed via ANOVA with Tukey post-hoc analysis.
ConclusionOverall, these findings demonstrate the ability of BPP to influence dendritic and T-cell responses in NSCLC via coordinated transcriptional and chromatinremodelling activities.
Graphical abstract