Barleria extracts containing barlerin and verbascoside boost immunity and regulate CYP450 gene in prostate cancer.

Barleria species have been traditionally utilized for medicinal purposes. This study provides a comprehensive analysis of six Barleria leaf extracts, namely B. cristata, B. lupulina, B. prionitis, B. repens, B. siamensis, and B. strigosa, to elucidate their metabolite composition, toxicity, immunomodulatory functions, and roles in cytochrome P450 (CYP) gene expression. The findings indicate that two key metabolites, barlerin and verbascoside, are present in all six Barleria extracts, with B. siamensis exhibiting the highest amount of these compounds at 0.43 mg/g (barlerin) and 1.02 mg/g (verbascoside) of dried leaf, respectively. In terms of toxicological effects, B. cristata and B. siamensis demonstrated significant anti-proliferative activity against PC-3 cells by inducing DNA damage, enhancing apoptosis, and obstructing the cell cycle. However, these extracts did not exert cytotoxic effects on PBMCs, HPrEC, and THLE-3. Conversely, B. strigosa extract exhibited mild toxicity towards HPrECs and moderate toxicity towards THLE-3 cells. Furthermore, treatment with these extracts activated PBMCs, leading to the upregulation of cytokine genes, including IL-2, IL-10, IL-12, IL-15, IL-21, and IFN-γ, which promoted cytotoxicity for PC-3 cells. Additionally, B. siamensis extract significantly suppressed the expression of CYP450 genes, including CYP1A2, CYP3A4, CYP2D6, and CYP2E1, whereas B. strigosa extract induced the overexpression of CYP2E1. In conclusion, Barleria extracts containing barlerin and verbascoside exhibit immunomodulatory properties by activating immune cells to target cancer cells. Moreover, these extracts influence the expression of CYP450 genes, potentially impacting their bioavailability and therapeutic efficacy.