Zhang Lingxiao, Yang Chenghao, Ding Xinyue, Zhang Hui, Luan Yuling, Tang Yueer, Liu Zongjun
Department of Cardiology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Department of Cardiology, The Second People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China.
Curr Comput Aided Drug Des. 2024 Oct 17. doi: 10.2174/0115734099330183241008071642.
Berberine (BBR), also known as berberine hydrochloride, was isolated from the rhizomes of the Coptis chinensis. Studies have reported that BBR plays an important role in glycolipid metabolism, including insulin (IR). The targets, and molecular mechanisms of BBR against hyperlipid-induced IR is worthy to be further studied.
The related targets of BBR were identified via Pharmmapper database and relevant targets of diabetes were obtained through GeneCards and Online Mendelian Inheritance in Man (OMIM) database. The common targets were employed with the STRING database and visualized with the protein-protein interactions (PPI) network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to explore the biological progress and pathways. In vitro, human hepatocellular carcinomas (HepG2) cell was used as experimental cell line, and an insulin resistant HepG2 cell model (IR-HepG2) was constructed using free fatty acid induction. After intervention with BBR, glucose consumption and uptake in HepG2 cells were observed. Molecular docking was used to test the interaction between BBR and key targets, and real-time fluorescence quantitative PCR was used to detect the regulatory effect of BBR on related targets.
262 overlapped targets were extracted from BBR and diabetes. In the KEGG enrichment analysis, the peroxisome proliferator activated receptor (PPAR) signaling pathway was included. In vitro experiments, BBR can significantly increase sugar consumption and uptake in IR HepG2 cells, while PPAR inhibitors can weaken the effect of BBR on IR-HepG2.
The PPAR signaling pathway is one of the important pathways for BBR to improve high-fat-induced insulin resistance in HepG2 cells.
黄连素（BBR），又称盐酸小檗碱，是从黄连根茎中分离得到的。研究报道BBR在糖脂代谢中发挥重要作用，包括胰岛素抵抗（IR）。BBR抗高脂诱导的IR的靶点及分子机制值得进一步研究。
通过Pharmmapper数据库鉴定BBR的相关靶点，并通过GeneCards和人类孟德尔遗传在线（OMIM）数据库获取糖尿病的相关靶点。将共同靶点用于STRING数据库，并通过蛋白质-蛋白质相互作用（PPI）网络进行可视化。进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析以探索生物学进程和途径。在体外，使用人肝癌细胞（HepG2）作为实验细胞系，并使用游离脂肪酸诱导构建胰岛素抵抗HepG2细胞模型（IR-HepG2）。用BBR干预后，观察HepG2细胞中的葡萄糖消耗和摄取。分子对接用于测试BBR与关键靶点之间的相互作用，实时荧光定量PCR用于检测BBR对相关靶点的调节作用。
从BBR和糖尿病中提取出262个重叠靶点。在KEGG富集分析中，包括过氧化物酶体增殖物激活受体（PPAR）信号通路。体外实验中，BBR可显著增加IR HepG2细胞中的糖消耗和摄取，而PPAR抑制剂可减弱BBR对IR-HepG2的作用。
PPAR信号通路是BBR改善HepG2细胞中高脂诱导的胰岛素抵抗的重要途径之一。
