Xiong Wei, Yang Ce, Xia Jing, Wang Wenxiang, Li Ning
Chongqing Three Gorges Medical College, Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing, China.
Front Pharmacol. 2023 Sep 18;14:1197418. doi: 10.3389/fphar.2023.1197418. eCollection 2023.
Ganoderma lucidum (G. lucidum) is a popular traditional remedy medicine used in Asia to promote health and longevity, which has also been highlighted for anti-cancer effects. This study investigated the molecular pharmacological mechanism of G. lucidum triterpenes in influencing intestinal flora imbalance in non-hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) based on 16S rRNA sequencing technology and network pharmacology analysis. 16S rRNA sequencing data of fecal samples from normal controls and HCC patients were obtained from the SRA database. G. lucidum triterpenes and HCC-related targets were screened by BATMAN-TCM, ETCM, and GeneCards databases. The TCGA-LIHC dataset was downloaded through the TCGA database to analyze the differential expression of key genes. NHBV-related HCC-related transcriptome RNA sequencing dataset was downloaded via the GEO database. Abundance of intestinal flora in the HBV-related HCC and NHBV-related samples was higher than that of control samples. The intestinal flora of NHBV samples was mainly enriched in apoptosis and p53 pathways. Totally, 465 G. lucidum triterpenes-related targets were intersected with 4186 HCC-related targets, yielding 176 intersected targets. Among them, apoptosis and p53 pathway factors were located at the core of the protein-protein interactions network. Ganosporelactone B, the active component of G. lucidum triterpenes, had the lowest binding free energy to CASP3. CASP3 expression were upregulated in HCC tissue samples, and had higher predictive value in NHBV-related HCC patients. Therefore, Ganosporelactone B, the active ingredient of G. lucidum triterpenes, improves the imbalance of intestinal flora and ultimately curtails development of NHBV-related HCC.
灵芝是亚洲一种广受欢迎的传统药物，用于促进健康和长寿，其抗癌作用也备受关注。本研究基于16S rRNA测序技术和网络药理学分析，探讨了灵芝三萜影响非乙型肝炎病毒（HBV）相关肝细胞癌（HCC）肠道菌群失衡的分子药理机制。从SRA数据库获取正常对照和HCC患者粪便样本的16S rRNA测序数据。通过BATMAN-TCM、ETCM和GeneCards数据库筛选灵芝三萜和HCC相关靶点。通过TCGA数据库下载TCGA-LIHC数据集，分析关键基因的差异表达。通过GEO数据库下载非HBV相关HCC相关转录组RNA测序数据集。HBV相关HCC和非HBV相关样本中肠道菌群的丰度高于对照样本。非HBV样本的肠道菌群主要富集于细胞凋亡和p53通路。总共，465个灵芝三萜相关靶点与4186个HCC相关靶点相交，产生176个相交靶点。其中，细胞凋亡和p53通路因子位于蛋白质-蛋白质相互作用网络的核心。灵芝三萜的活性成分甘氨孢内酯B与CASP3的结合自由能最低。CASP3在HCC组织样本中表达上调，在非HBV相关HCC患者中具有较高的预测价值。因此，灵芝三萜的活性成分甘氨孢内酯B改善肠道菌群失衡，最终抑制非HBV相关HCC的发展。
