Kaewdaungdee Sanit, Sham Zi Wei, Ho Hao Xuan, Lee Shiou Yih, Tanee Tawatchai, Benoit Yannick D, Liehr Thomas, Daduang Sakda, Sudmoon Runglawan, Chaveerach Arunrat
Department of Biology, Faculty of Science, Khon Kaen University, Khon Kaen, Thailand.
Faculty of Health and Life Sciences, INTI International University, Nilai, Negeri Sembilan, Malaysia.
Sci Rep. 2025 Jul 1;15(1):21942. doi: 10.1038/s41598-025-07397-5.
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.
传统上，假杜鹃属植物已被用于药用。本研究对六种假杜鹃属植物的叶提取物进行了全面分析，这六种植物分别是头花蓼、黄毛假杜鹃、刺枝假杜鹃、匍匐假杜鹃、暹罗假杜鹃和具梗假杜鹃，以阐明它们的代谢物组成、毒性、免疫调节功能以及在细胞色素P450（CYP）基因表达中的作用。研究结果表明，所有六种假杜鹃属植物提取物中均存在两种关键代谢物——巴列林和毛蕊花糖苷，其中暹罗假杜鹃中这两种化合物的含量最高，干叶中分别为0.43毫克/克（巴列林）和1.02毫克/克（毛蕊花糖苷）。在毒理学效应方面，头花蓼和暹罗假杜鹃通过诱导DNA损伤、增强细胞凋亡和阻碍细胞周期，对PC-3细胞表现出显著的抗增殖活性。然而，这些提取物对PBMC、HPrEC和THLE-3没有细胞毒性作用。相反，具梗假杜鹃提取物对HPrEC表现出轻度毒性，对THLE-3细胞表现出中度毒性。此外，用这些提取物处理可激活PBMC，导致细胞因子基因上调，包括IL-2、IL-10、IL-12、IL-15、IL-21和IFN-γ，从而促进对PC-3细胞的细胞毒性。此外，暹罗假杜鹃提取物显著抑制CYP450基因的表达，包括CYP1A2、CYP3A4、CYP2D6和CYP2E1，而具梗假杜鹃提取物诱导CYP2E1的过表达。总之，含有巴列林和毛蕊花糖苷的假杜鹃属植物提取物通过激活免疫细胞靶向癌细胞而表现出免疫调节特性。此外，这些提取物影响CYP450基因的表达，可能会影响它们的生物利用度和治疗效果。
