Investigation of the active ingredients and pharmacological mechanisms of Porana sinensis Hemsl. Against rheumatoid arthritis using network pharmacology and experimental validation

PLoS One. 2022 Mar 2;17(3):e0264786. doi: 10.1371/journal.pone.0264786. eCollection 2022.

Abstract

Background: Porana sinensis Hemsl. has been widely used as a substitute for Erycibes Caulis to treat rheumatoid arthritis (RA) in traditional Chinese medicine (TCM). However, little is known about the active ingredients and pharmacological mechanisms that mediate the action of P. sinensis against RA.

Methods: The compounds contained in P. sinensis were analyzed by Q Exactive Focus mass spectrometer. The active constituents and pharmacological mechanism of P. sinensis against RA were clarified using a network pharmacology-based investigation. LPS-induced RAW 264.7 cells was used to verify anti-inflammatory effects of the active compounds screened by network pharmacology. Collagen-induced arthritis model was used to further investigate the mechanism of P. sinensis against RA.

Results: The potential components and targets of P. sinensis against RA were analyzed using network pharmacology, and five compounds, twenty-five targets, and eight pathways were identified. Experimental validation suggested that P. sinensis extract and five compounds (esculetin, umbelliferone, trans-N-feruloyltyramine, caffeic acid and scopolin) could inhibit the release of inflammatory mediators (NO, TNF-α, IL-1β and IL-6) in LPS-induced RAW 264.7 cell. P. sinensis extract attenuated the severity, pathological changes, and release of cytokines (IL-6 and HIF-1α) during RA progression by regulating the PI3K/AKT and HIF-1 pathways.

Conclusion: The study provides a basis for the application of P. sinensis against RA. Our findings may provide suggestions for developing P. sinensis into a substitute for Erycibes Caulis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental* / drug therapy
  • Arthritis, Rheumatoid* / metabolism
  • Drugs, Chinese Herbal* / adverse effects
  • Interleukin-6 / therapeutic use
  • Lipopolysaccharides / adverse effects
  • Network Pharmacology
  • Phosphatidylinositol 3-Kinases

Substances

  • Drugs, Chinese Herbal
  • Interleukin-6
  • Lipopolysaccharides

Grants and funding

This work was financially supported by the National Natural Science Foundation of China [grant numbers 81973419, 81603264]; Key Research and Development Program of Shaanxi [grant number 2020SF-328]; Shaanxi Administration of Traditional Chinese Medicine Projects [grant number 2021-PY-003]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.