Isovitexin alleviates acute gouty arthritis in rats by inhibiting inflammation via the TLR4/MyD88/NF-κB pathway

Pharm Biol. 2021 Dec;59(1):1326-1333. doi: 10.1080/13880209.2021.1979595.

Abstract

Context: The prevalence of gout has greatly increased, and it has become the most common inflammatory arthritis in men. Isovitexin possesses anti-inflammatory and antioxidant properties.

Objective: We explored the effects of isovitexin on rats with acute gouty arthritis (GA).

Materials and methods: Fifty-four Sprague-Dawley rats were assigned to five groups: sham, model, positive (colchicine, 0.3 mg/kg), isovitexin (100 mg/kg), TLR4 inhibitor (TAK-242, 3 mg/kg) and isovitexin + TAK-242. The gait of rats and the ankle joint swelling index were monitored. The levels of tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6, and pathological changes in the synovial tissues were determined.

Results: Isovitexin significantly reduced the ankle joint swelling index at day 7 compared to that in the model group (4.39 ± 1.01 vs. 6.09 ± 1.31). Moreover, isovitexin alleviated the infiltration of inflammatory cells and ameliorated the proliferation of synovial cells. The levels of TNF-α (93.42 ± 5.02 pg/mL), IL-1β (25.46 ± 1.91 pg/mL) and IL-6 (194.71 ± 7.92 pg/mL) in the isovitexin group were significantly lower than in the model group (129.39 ± 5.43, 39.60 ± 2.71 and 223.77 ± 5.35 pg/mL). The expression of TLR4, MyD88 and p-NF-κB-p65 was remarkably decreased after isovitexin and colchicine treatment. The effect of isovitexin was similar to that colchicine. Furthermore, the combination of isovitexin and TAK-242 had better effect, and there was no significantly difference with colchicine treatment.

Discussion and conclusions: Isovitexin ameliorates joint inflammation in acute GA via the TLR4/MyD88/NF-κB pathway. Isovitexin may be a potential substitute medicine for GA.

Keywords: Inflammatory factors; TLR4 inhibitor; pathological changes.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology
  • Apigenin / pharmacology*
  • Arthritis, Gouty / drug therapy*
  • Arthritis, Gouty / pathology
  • Colchicine / pharmacology
  • Disease Models, Animal
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Male
  • Myeloid Differentiation Factor 88 / metabolism
  • NF-kappa B / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sulfonamides / pharmacology
  • Toll-Like Receptor 4 / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Myd88 protein, rat
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • Sulfonamides
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate
  • Apigenin
  • isovitexin
  • Colchicine