Department of Pharmaceutical Botany, Medical University of Lublin, 1 Chodźki St., 20-093 Lublin, Poland.
Department of Medical Biology, Institute of Rural Health, 20-090 Lublin, Poland.
Int J Mol Sci. 2024 Apr 27;25(9):4786. doi: 10.3390/ijms25094786.
L. () is a shrub that has been widely used in European folk medicine as an anti-inflammatory and antimicrobial agent. The purpose of our study was to elucidate the mechanisms of the chemopreventive action of the plant's methanolic root extract (BVR) against colon cancer cells. Studies were conducted in human colon adenocarcinoma cell lines (LS180 and HT-29) and control colon epithelial CCD841 CoN cells. According to the MTT assay, after 48 h of cell exposure, the IC values were as follows: 4.3, 46.1, and 50.2 µg/mL for the LS180, HT-29, and CCD841 CoN cells, respectively, showing the greater sensitivity of the cancer cells to BVR. The Cell Death Detection ELISAPLUS kit demonstrated that BVR induced programmed cell death only against HT-29 cells. Nuclear double staining revealed the great proapoptotic BVR properties in HT-29 cells and subtle effect in LS180 cells. RT-qPCR with the relative quantification method showed significant changes in the expression of genes related to apoptosis in both the LS180 and HT-29 cells. The genes (126.86-421.43%), (240-286.02%), (177.19-247.83%), and (157.99-243.75%) had a significantly elevated expression, while BCL2 (25-52.03%) had a reduced expression compared to the untreated control. Furthermore, in a panel of antioxidant tests, BVR showed positive effects (63.93 ± 0.01, 122.92 ± 0.01, and 220.29 ± 0.02 mg Trolox equivalents (TE)/g in the DPPH•, ABTS•+, and ORAC assays, respectively). In the lipoxygenase (LOX) inhibition test, BVR revealed 62.60 ± 0.87% of enzyme inhibition. The chemical composition of BVR was determined using a UHPLC-UV-CAD-MS/MS analysis and confirmed the presence of several known alkaloids, including berberine, as well as other alkaloids and two derivatives of hydroxycinnamic acid (ferulic and sinapic acid hexosides). The results are very promising and encourage the use of BVR as a comprehensive chemopreventive agent (anti-inflammatory, antioxidant, and pro-apoptotic) in colorectal cancer, and were widely discussed alongside data from the literature.
() 是一种灌木，在欧洲民间医学中被广泛用作抗炎和抗菌剂。我们的研究目的是阐明该植物甲醇根提取物 (BVR) 对结肠癌细胞的化学预防作用的机制。研究在人结肠腺癌细胞系 (LS180 和 HT-29) 和对照结肠上皮 CCD841 CoN 细胞中进行。根据 MTT 测定，细胞暴露 48 小时后，LS180、HT-29 和 CCD841 CoN 细胞的 IC 值分别为 4.3、46.1 和 50.2µg/mL，表明癌细胞对 BVR 更敏感。细胞死亡检测 ELISA PLUS 试剂盒表明 BVR 仅诱导 HT-29 细胞发生程序性细胞死亡。核双重染色显示 BVR 在 HT-29 细胞中具有很强的促凋亡特性，而在 LS180 细胞中则具有轻微的作用。采用相对定量方法的 RT-qPCR 显示，LS180 和 HT-29 细胞中与凋亡相关的基因表达均发生显著变化。基因 (126.86-421.43%)、 (240-286.02%)、 (177.19-247.83%) 和 (157.99-243.75%) 的表达显著升高，而 BCL2 (25-52.03%) 的表达则降低与未经处理的对照相比。此外，在一组抗氧化测试中，BVR 在 DPPH•、ABTS•+ 和 ORAC 测定中分别显示出阳性效应 (63.93±0.01、122.92±0.01 和 220.29±0.02mg Trolox 当量 (TE)/g)。在脂氧合酶 (LOX) 抑制试验中，BVR 显示出 62.60±0.87%的酶抑制作用。使用 UHPLC-UV-CAD-MS/MS 分析确定了 BVR 的化学成分，并证实了几种已知生物碱的存在，包括小檗碱以及其他生物碱和两种羟基肉桂酸衍生物 (阿魏酸和芥子酸己糖苷)。这些结果非常有希望，并鼓励将 BVR 用作结直肠癌的综合化学预防剂 (抗炎、抗氧化和促凋亡)，并与文献中的数据一起进行了广泛讨论。
