Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, P.R. China.
Mol Med Rep. 2020 Dec;22(6):5163-5180. doi: 10.3892/mmr.2020.11602. Epub 2020 Oct 14.
Intestinal surface epithelial cells (IECs) have long been considered as an effective barrier for maintaining water and electrolyte balance, and are involved in the mechanism of nutrient absorption. When intestinal inflammation occurs, it is often accompanied by IEC malfunction. Berberine (BBR) is an isoquinoline alkaloid found in numerous types of medicinal plants, which has been clinically used in China to treat symptoms of gastrointestinal pathogenic bacterial infection, especially bacteria‑induced diarrhea and inflammation. In the present study, IEC‑18 rat intestinal epithelial cells were treated with lipopolysaccharide (LPS) to establish an in vitro model of epithelial cell inflammation, and the cells were subsequently treated with BBR in order to elucidate the anti‑inflammatory mechanism. Transcriptome data were then searched to find the differentially expressed genes (DEGs) compared between two of the treatment groups (namely, the LPS and LPS+BBR groups), and DEGs were analyzed using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Weighted Gene Correlation Network Analysis and Interactive Pathways Explorer to identify the functions and pathways enriched with DEGs. Finally, reverse transcription‑quantitative PCR was used to verify the transcriptome data. These experiments revealed that, comparing between the LPS and LPS+BBR groups, the functions and pathways enriched in DEGs were 'DNA replication', 'cell cycle', 'apoptosis', 'leukocyte migration' and the 'NF‑κB and AP‑1 pathways'. The results revealed that BBR is able to restrict DNA replication, inhibit the cell cycle and promote apoptosis. It can also inhibit the classic inflammatory pathways, such as those mediated by NF‑κB and AP‑1, and the expression of various chemokines to prevent the migration of leukocytes. According to transcriptomic data, BBR can exert its anti‑inflammatory effects by regulating a variety of cellular physiological activities, including cell cycle, apoptosis, inflammatory pathways and leukocyte migration.
肠表面上皮细胞（IECs）长期以来一直被认为是维持水和电解质平衡的有效屏障，并参与营养吸收的机制。当肠道炎症发生时，通常伴随着 IEC 功能障碍。小檗碱（BBR）是一种在多种药用植物中发现的异喹啉生物碱，在中国临床上用于治疗胃肠道致病细菌感染的症状，特别是细菌引起的腹泻和炎症。在本研究中，用脂多糖（LPS）处理 IEC-18 大鼠肠上皮细胞，建立上皮细胞炎症的体外模型，然后用 BBR 处理细胞，以阐明其抗炎机制。然后搜索转录组数据，以找到与两个处理组（即 LPS 和 LPS+BBR 组）相比差异表达的基因（DEGs），并使用基因本体论、京都基因与基因组百科全书、加权基因相关网络分析和交互式途径浏览器对 DEGs 进行分析，以确定富集 DEGs 的功能和途径。最后，使用逆转录-定量 PCR 验证转录组数据。这些实验表明，与 LPS 和 LPS+BBR 组相比，DEGs 富集的功能和途径为“DNA 复制”、“细胞周期”、“细胞凋亡”、“白细胞迁移”和“NF-κB 和 AP-1 途径”。结果表明，BBR 能够限制 DNA 复制，抑制细胞周期并促进细胞凋亡。它还可以抑制经典的炎症途径，如 NF-κB 和 AP-1 介导的途径，以及各种趋化因子的表达，以防止白细胞迁移。根据转录组数据，BBR 可以通过调节多种细胞生理活动发挥抗炎作用，包括细胞周期、细胞凋亡、炎症途径和白细胞迁移。
