Network Pharmacology and Pharmacological Evaluation Reveals the Mechanism of the Sanguisorba Officinalis in Suppressing Hepatocellular Carcinoma

Nan Jiang; Hong Li; Yueshan Sun; Jing Zeng; Fei Yang; Fahsai Kantawong; Jianming Wu

doi:10.3389/fphar.2021.618522

Network Pharmacology and Pharmacological Evaluation Reveals the Mechanism of the Sanguisorba Officinalis in Suppressing Hepatocellular Carcinoma

Front Pharmacol. 2021 Mar 4:12:618522. doi: 10.3389/fphar.2021.618522. eCollection 2021.

Authors

Nan Jiang^{1

2

3}, Hong Li^{2

4}, Yueshan Sun^{2

4}, Jing Zeng^{2

4}, Fei Yang^{2

4}, Fahsai Kantawong¹, Jianming Wu^{1

2

4}

Affiliations

¹ Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand.
² School of Pharmacy, Southwest Medical University, Luzhou, China.
³ International Education School, Southwest Medical University, Luzhou, China.
⁴ Education Ministry Key Laboratory of Medical Electrophysiology, Sichuan Key Medical Laboratory of New Drug Discovery and Drugability Evaluation, Luzhou Key Laboratory of Activity Screening and Drugability Evaluation for Chinese Materia Medica, Southwest Medical University, Luzhou, China.

Abstract

Background: Sanguisorba Officinalis L. (SO) is a well-known traditional Chinese medicine (TCM), commonly applied to treat complex diseases, such as anticancer, antibacterial, antiviral, anti-inflammatory, anti-oxidant and hemostatic effects. Especially, it has been reported to exert anti-tumor effect in various human cancers. However, its effect and pharmacological mechanism on hepatocellular carcinoma (HCC) remains unclear. Methods: In this study, network pharmacology approach was applied to characterize the underlying mechanism of SO on HCC. Active compounds and potential targets of SO, as well as related genes of HCC were obtained from the public databases, the potential targets and signaling pathways were determined by protein-protein interaction (PPI), gene ontology (GO) and pathway enrichment analyses. And the compound-target and target-pathway networks were constructed. Subsequently, in vitro experiments were also performed to further verify the anticancer effects of SO on HCC. Results: By using the comprehensive network pharmacology analysis, 41 ingredients in SO were collected from the corresponding databases, 12 active ingredients screened according to their oral bioavailability and drug-likeness index, and 258 potential targets related to HCC were predicted. Through enrichment analysis, SO was found to show its excellent therapeutic effects on HCC through several pathways, mainly related to proliferation and survival via the EGFR, PI3K/AKT, NFκB and MAPK signaling pathways. Additionally, in vitro, SO was found to inhibit cell proliferation, induce apoptosis and down-regulate cell migration and invasion in various HCC cells. Moreover, western blot analysis showed that SO treatment down-regulated the expression of p-EGFR, p-PI3K, p-AKT, p-NFκB and p-MAPK proteins in HepG2 cells. These results validated that SO exerted its therapeutic effects on HCC mainly by the regulation of cell proliferation and survival via the EGFR/MAPK and EGFR/PI3K/AKT/NFκB signaling pathways. Conclusion: Taken together, this study, revealed the anti-HCC effects of SO and its potential underlying therapeutic mechanisms in a multi-target and multi-pathway manner.

Keywords: EGFR/MAPK signaling; PI3K/Akt signal pathway; Sanguisorba officinalis L; cell proliferation; hepatocellular carcinoma; network pharmacology.