Anti-arthritic activity of luteolin in Freund's complete adjuvant-induced arthritis in rats by suppressing P2X4 pathway

Chem Biol Interact. 2015 Jan 25:226:82-7. doi: 10.1016/j.cbi.2014.10.031. Epub 2014 Nov 6.

Abstract

To investigate anti-arthritic activity of luteolin (Lut) in Freund's complete adjuvant (FCA)-induced arthritis (AA) in rats. AA was induced by injecting with Freund's complete adjuvant (FCA). Male rats were randomly divided into five groups with 10 mice in each group: (1) control group (saline), (2) AA group, (3) AA+Diclofenac Sodium (AA+DS, 5 mg/kg), (4) AA+Lut (20 mg/kg), (5) AA+Lut (40 mg/kg). Male SD rats were subjected to treatment with Lut at 10 and 20 mg/kg from days 18 to 24 after immunization. Arthritic scores, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-17 (IL-17), paw histopathology and the proteins of P2X4 pathway were assessed at the end of the experiment. Lut reduced the severity of arthritic scores during the experimental period as compared with positive control (RA). Lut significantly suppressed TNF-α, IL-6, IL-1β and IL-17 as compared with RA group. Histopathological examination indicated that Lut alleviated infiltration of inflammatory cells and synovial hyperplasia as well as protected joint destruction. Lut significantly suppressed P2X4, NLRP1, ASC, and Caspase-1p10. Lut may be a potential preventive or therapeutic candidate for the treatment of inflammation and arthritis.

Keywords: Arthritis; Freund’s complete adjuvant; Luteolin; P2X4.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Apoptosis Regulatory Proteins / metabolism
  • Arthritis, Experimental / chemically induced*
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / metabolism
  • Arthritis, Experimental / pathology
  • Body Weight / drug effects
  • CARD Signaling Adaptor Proteins
  • Caspase 1 / metabolism
  • Cytokines / biosynthesis
  • Freund's Adjuvant / adverse effects*
  • Luteolin / pharmacology*
  • Luteolin / therapeutic use
  • Male
  • Mice
  • Rats
  • Receptors, Purinergic P2X4 / metabolism*
  • Signal Transduction / drug effects*

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • CARD Signaling Adaptor Proteins
  • Cytokines
  • NALP1 protein, mouse
  • Pycard protein, mouse
  • Receptors, Purinergic P2X4
  • Freund's Adjuvant
  • Caspase 1
  • Luteolin