Therapeutic effects of Panax notoginseng saponins in rheumatoid arthritis: network pharmacology and experimental validation

ABSTRACT

Panax notoginseng saponins (PNS) have been reported to have good anti-inflammatory effects. However, the anti-inflammatory effect mechanism in rheumatoid arthritis (RA) remains unknown. The focus of this research was to investigate the molecular mechanism of PNS in the treatment of RA. The primary active components of PNS were tested utilizing the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and Analysis Platform based on oral bioavailability and drug-likeness. The target databases for knee osteoarthritis were created using GeneCards and Online Mendelian Inheritance in Man (OMIM). The visual interactive network structure ‘active component – action target – illness’ was created using Cytoscape software. A protein interaction network was built, and associated protein interactions were analyzed using the STRING database. The key targets were analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) biological process enrichment analyses. The effects of PNS on cell growth were studied in human umbilical vein endothelial cells (HUVECs) treated with various doses of PNS, and the optimum concentration of PNS was identified. PNS was studied for its implication on angiogenesis and migration. The active components of PNS had 114 common targets, including cell metabolism and apoptosis, according to the network analysis. The therapeutic effects of the PNS components were suggested to be mediated through apoptotic and cytokine signaling pathways. In vitro, PNS therapy boosted HUVEC proliferation. Wound healing, Boyden chamber and tube formation tests suggested that PNS may increase HUVEC activity and capillary-like tube branching. This study clarified that for the treatment of RA, PNS has multisystem, multicomponent, and multitargeted properties.

GRAPHICAL ABSTRACT

KEYWORDS:

• Rheumatoid arthritis
• Panax notoginseng saponins
• network pharmacology
• molecular mechanism
• traditional Chinese medicine

Acknowledgements

The authors thank the Scientific Research Center at the Second Affiliated Hospital of Harbin Medical University for technical support.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

XNM, XZ and XTW conceived and wrote the manuscript. KYH and BS created the figures and table. LLW and DQL revised and approved the final manuscript. Every author read and approved the final manuscript. XNM and XZ contributed equally to this work and share first authorship.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/21655979.2022.2086379

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81772362) and Excellent Youth Foundation of Heilongjiang Province of China (Grant JQ2020H003).