AUTHOR=Zhang Weijia , Sang Shuyi , Peng Chang , Li George Q. , Ou Ling , Feng Zhong , Zou Yuanjing , Yuan Yuemei , Yao Meicun 

TITLE=Network Pharmacology and Transcriptomic Sequencing Analyses Reveal the Molecular Mechanism of Sanguisorba officinalis Against Colorectal Cancer

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.807718

DOI=10.3389/fonc.2022.807718

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Colorectal cancer (CRC) is the most common malignant cancer worldwide. <italic>Sanguisorba officinalis</italic> has been shown to have anti-inflammatory, anti-bacterial, antioxidant, and anti-tumor effects, while its molecular mechanism against CRC remains unclear. The aim of this study is to explore the underlying mechanism of <italic>S. officinalis</italic> against CRC cell lines using network pharmacology and transcriptomic sequencing methods.</p></sec><sec><title>Method</title><p>Firstly, the active ingredients and potential targets of <italic>S. officinalis</italic> against CRC were screened from databases. Secondly, the networks of ingredient–target, ingredient–target–CRC and protein–protein interaction were constructed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of network pharmacology and transcriptomic sequencing were performed. Finally, the effect of <italic>S. officinalis</italic> against CRC was verified by <italic>in vitro</italic> experiments.</p></sec><sec><title>Results</title><p>In total, 14 active ingredients and 273 potential targets against CRC were identified in <italic>S. officinalis</italic> by network pharmacology. PI3K–Akt, HIF-1, and MAPK signaling pathways related to cell proliferation were regulated by <italic>S. officinalis</italic> in enrichment analyses and transcriptomic sequencing. <italic>In vitro</italic>, <italic>S. officinalis</italic> inhibited the proliferation and migration of CRC cells and arrested the cell cycle at the G0–G1 phase. The western blot showed that <italic>S. officinalis</italic> downregulated the expression of p-PI3K, p-Akt, HIF-1A, VEGFA, cyclin D1, c-Myc, and p-MAPK proteins in CRC cells.</p></sec><sec><title>Conclusion</title><p>In conclusion, network pharmacology and transcriptomic sequencing analyses, in combination with <italic>in vitro</italic> studies, have been successfully applied to study the underlying mechanism of <italic>S. officinalis</italic> against CRC cells. Our results demonstrate that <italic>S. officinalis</italic> suppresses the proliferation, survival, and migration of CRC cells through regulating the PI3K–Akt, HIF-1, and MAPK signaling pathways.</p></sec>