Hybertson Brooks M, Gao Bifeng, Bose Swapan, McCord Joe M
Pathways Bioscience, Aurora, CO 80045, USA.
Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Antioxidants (Basel). 2019 May 3;8(5):119. doi: 10.3390/antiox8050119.
Bioactive phytochemicals in , , and have a long history of human use to promote health. In this study we examined the cellular effects of a combination of extracts from these plant sources based on specified levels of their carnosol/carnosic acid, withaferin A, and luteolin levels, respectively. Individually, these bioactive compounds have previously been shown to activate the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor, which binds to the antioxidant response element (ARE) and regulates the expression of a wide variety of cytoprotective genes. We found that combinations of these three plant extracts act synergistically to activate the Nrf2 pathway, and we identified an optimized combination of the three agents which we named PB125 for use as a dietary supplement. Using microarray, quantitative reverse transcription-PCR, and RNA-seq technologies, we examined the gene expression induced by PB125 in HepG2 (hepatocellular carcinoma) cells, including canonical Nrf2-regulated genes, noncanonical Nrf2-regulated genes, and genes which appear to be regulated by non-Nrf2 mechanisms. Ingenuity Pathway Analysis identified Nrf2 as the primary pathway for gene expression changes by PB125. Pretreatment with PB125 protected cultured HepG2 cells against an oxidative stress challenge caused by cumene hydroperoxide exposure, by both cell viability and cell injury measurements. In summary, PB125 is a phytochemical dietary supplement comprised of extracts of three ingredients, , , and , with specified levels of carnosol/carnosic acid, withaferin A, and luteolin, respectively. Each ingredient contributes to the activation of the Nrf2 pathway in unique ways, which leads to upregulation of cytoprotective genes and protection of cells against oxidative stress and supports the use of PB125 as a dietary supplement to promote healthy aging.
迷迭香、印度萝芙木和黄芩中的生物活性植物化学物质在人类促进健康方面有着悠久的使用历史。在本研究中，我们根据这些植物来源提取物中鼠尾草酸/鼠尾草酚、阿魏酰基去氧鬼臼毒素和木犀草素的特定含量水平，研究了它们组合后的细胞效应。此前已表明，这些生物活性化合物各自能够激活核因子红细胞2相关因子2（Nrf2）转录因子，该转录因子与抗氧化反应元件（ARE）结合并调节多种细胞保护基因的表达。我们发现，这三种植物提取物的组合具有协同作用，可激活Nrf2信号通路，并且我们确定了这三种成分的一种优化组合，将其命名为PB125，用作膳食补充剂。我们使用微阵列、定量逆转录PCR和RNA测序技术，研究了PB125在HepG2（肝癌）细胞中诱导的基因表达，包括经典Nrf2调控基因、非经典Nrf2调控基因以及似乎受非Nrf2机制调控的基因。通路分析软件（IPA）确定Nrf2是PB125引起基因表达变化的主要信号通路。通过细胞活力和细胞损伤测量发现，用PB125预处理可保护培养的HepG2细胞免受异丙苯过氧化氢暴露引起的氧化应激挑战。总之，PB125是一种植物化学膳食补充剂，由迷迭香、印度萝芙木和黄芩三种成分的提取物组成，分别含有特定含量的鼠尾草酸/鼠尾草酚、阿魏酰基去氧鬼臼毒素和木犀草素。每种成分都以独特的方式促进Nrf2信号通路的激活，从而导致细胞保护基因的上调，并保护细胞免受氧化应激，支持将PB125用作促进健康衰老的膳食补充剂。
