Abstract
Purpose: To investigate the effect of Hedyotis diffusa Willd extract (HDWE) on gouty arthritis in rats.Method: Monosodium urate (MSU) crystal was injected into the ankle joint of rats to establish a rat model of gouty arthritis. HDWE (4.8, 9.6 and 19.2 g/kg) was administered to the rats treated with MSU crystals. The walking behavior of the rats was observed daily, and the gait score was calculated to evaluate the Oswestry disability index of rats. Levels of IL-1β and TNF-α in lavage fluid of articularcavities were measured using enzyme linked immunosorbent assay (ELISA) kits. The synovial tissues of joint of control, model and 19.2 g/kg HDWE group rats were obtained and NLRP3 inflammasome was analysed by Western blot.Results: The results showed that HDWE ameliorated the symptoms of gouty arthritis and gait score in rats significantly (p < 0.05). Further pharmacological experiments showed that all doses of HDWE decreased the levels of inflammatory cytokines IL-1β and TNF-α (p < 0.05), and inhibited NLRP3, caspase-1, ASC, IL-1β and IL-18 protein expressions of the lavage fluid of articular cavities in MSU crystal-treated rats (p < 0.01).Conclusion: The results indicate that HDWE exhibits a significant effect in ameliorating gouty arthritis via inhibition NLRP3 inflammasome, and thus is a potential new drug choice for the treatment of gouty arthritis.
 Keywords: Hedyotis diffusa, Caspase, Gouty arthritis, Inflammatory cytokines, NLRP3 inflammasom
Highlights
As an inflammatory arthritis, gouty arthritis is caused by monosodium urate (MSU) crystal deposition in and around the joints [1]
Studies have shown that NOD-like receptors containing a PYD3 (NLRP3) inflammasomes play a critical role in MSUinduced IL-1β secretion in macrophages [3]
Hedyotis diffusa Willd extract (HDWE) attenuated the levels of proinflammatory cytokines in Monosodium urate (MSU) crystalstreated rats To identify the alterations of pro-inflammatory cytokines after ankle injection of MSU crystals suspension, we determined the levels of proinflammatory cytokines in the lavage fluid of articular cavities collected at 24 h later of the last drug administration
Summary
Gouty arthritis is caused by monosodium urate (MSU) crystal deposition in and around the joints [1]. Sixty male rats (Sprague-Dawley, 200 – 220 g) were purchased from Hubei Experimental Animal Center (Wuhan, China) and were housed for one Homogenous suspensions of celecoxib was made with distilled water. At the 7th day of drug administration, rats were anesthetized with 20% urethane solution, and MSU crystals suspension (100 μL) or PBS (100 μL) was injected into the tibiotarsal joint (ankle) of rats. HDWE attenuated the levels of proinflammatory cytokines in MSU crystalstreated rats To identify the alterations of pro-inflammatory cytokines after ankle injection of MSU crystals suspension, we determined the levels of proinflammatory cytokines in the lavage fluid of articular cavities collected at 24 h later of the last drug administration. IL-1β and TNF-α levels of the lavage fluid of articular cavities in MSU crystals-treated rats were increased significantly (P < 0.01). In order to understand the effect of HDWE on joint, the effect of HDWE on the NLRP3 inflammasome protein expression was investigated
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