Investigation of the mechanism of action of Porana sinensis Hemsl. against gout arthritis using network pharmacology and experimental validation

J Ethnopharmacol. 2020 Apr 24:252:112606. doi: 10.1016/j.jep.2020.112606. Epub 2020 Jan 25.

Abstract

Ethnopharmacological relevance: Porana sinensis Hemsl. has been widely used to treat joint pain and rheumatoid arthritis in traditional Chinese medicine (TCM). Although evidence exists to support a pharmacological action of P. sinensis for the treatment of gout arthritis (GA), the underlying mechanism of action remains unknown due to it being a multi-component and multi-target agent.

Aim of the study: To clarify the active compounds and mechanism of P. sinensis against GA.

Materials and methods: The present study combined network pharmacology with experiments to clarify the mechanism of P. sinensis against GA. A protein-protein interaction network for gout was constructed to identify the potential drug targets, and molecular docking was subsequently performed to determine whether the protein was a target for the compounds of P. sinensis. KEGG pathway analysis was then conducted to elucidate the pathway involved in the P. sinensis-mediated treatment of gout. A rat model of GA was used to further investigate the mechanism of P. sinensis against GA.

Results: The network pharmacology study indicates that coumarins and chlorogenic acids of P. sinensis may serve as additives to GA treatment. P. sinensis played a role in the treatment of GA by regulating the PI3K-Akt, MAPK, NF-kappa B and toll-like receptor pathways and so on. Moreover, experimental validation suggests that P. sinensis extract significantly suppressed the expression of TLR2 and MyD88 mRNA, regulating the release of cytokines (IL-1β, IL-4 and TGF-β), lowering lipid peroxidation (MDA) and increasing antioxidant status (SOD).

Conclusion: The present study clarifies the mechanism of P. sinensis against GA, and provides evidence to support its clinical use.

Keywords: Anti-inflammatory; Experimental validation; Gout arthritis; Network pharmacology; Porana sinensis.

MeSH terms

  • Animals
  • Ankle Joint / drug effects
  • Ankle Joint / pathology
  • Arthritis, Gouty / drug therapy
  • Arthritis, Gouty / genetics
  • Arthritis, Gouty / metabolism*
  • Arthritis, Gouty / pathology
  • Chlorogenic Acid / pharmacology
  • Chlorogenic Acid / therapeutic use
  • Convolvulaceae*
  • Coumarins / pharmacology
  • Coumarins / therapeutic use
  • Cytokines / blood
  • Male
  • Molecular Docking Simulation
  • Myeloid Differentiation Factor 88 / genetics
  • Pharmacology / methods
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Protein Interaction Maps
  • Rats, Sprague-Dawley
  • Toll-Like Receptor 2 / genetics

Substances

  • Coumarins
  • Cytokines
  • Myd88 protein, rat
  • Myeloid Differentiation Factor 88
  • Plant Extracts
  • Tlr2 protein, rat
  • Toll-Like Receptor 2
  • Chlorogenic Acid