Abstract
BackgroundSi-Miao-San (SMS) is a well-known traditional Chinese medicine. This study aims to evaluate the anti-inflammatory effects of SMS on gouty arthritis and its potential mechanism of action.MethodsThe effects and mechanism of SMS were evaluated in monosodium urate (MSU)-treated mice or macrophages. The expression of cytokines and PI3K/Akt was analyzed using real-time PCR and Western blotting analyses. Macrophage polarization was assessed with immunofluorescence assays, real-time PCR, and Western blotting. Mass spectrometry was used to screen the active ingredients of SMS.ResultsPretreatment with SMS ameliorated MSU-induced acute gouty arthritis in mice with increased PI3K/Akt activation and M2 macrophage polarization in the joint tissues. In vitro, SMS treatment significantly inhibited MSU-triggered inflammatory response, increased p-Akt and Arg-1 expression in macrophages, and promoted M2 macrophage polarization. These effects of SMS were inhibited when PI3K/Akt activation was blocked by LY294002 in the macrophages. Moreover, SMS significantly reduced serum uric acid levels in the hyperuricemia mice. Using mass spectrometry, the plant hormones ecdysone and estrone were detected as the potentially effective ingredients of SMS.ConclusionSMS ameliorated MSU-induced gouty arthritis and inhibited hyperuricemia. The anti-inflammatory mechanism of SMS may exert anti-inflammatory effects by promoting M2 polarization via PI3K/Akt signaling. Ecdysone and estrone might be the potentially effective ingredients of SMS. This research may provide evidence for the application of SMS in the treatment of gout.
Highlights
Gouty arthritis is a common inflammatory arthropathy induced by monosodium urate (MSU) crystals deposited in joints and soft tissues [1,2,3]
We have recently shown that resident macrophages trigger the inflammation in gouty arthritis [21] while depletion of tissue resident macrophages or blocking M1 macrophages polarization significantly decreased IL-1b expression and neutrophil infiltration [22]
Mice were pretreated with different doses of SMS (1 or 10 mg/ kg.day) for 2 weeks, and acute gouty arthritis was induced by MSU
Summary
Gouty arthritis is a common inflammatory arthropathy induced by monosodium urate (MSU) crystals deposited in joints and soft tissues [1,2,3]. Hyperuricemia is the key pathophysiological condition for the development of symptomatic gout [4, 5]. The prevalence of hyperuricemia was about 2.6%-36.0% [6], the prevalence of gout was about 0.03%-15.3% [7]. Clinical remission can be achieved in most patients through anti-inflammatory treatment and urate-lowering therapy (ULT) [8,9,10]. It is imperative to explore new approaches for the treatment of gouty arthritis, especially with complementary and alternative medicine. This study aims to evaluate the anti-inflammatory effects of SMS on gouty arthritis and its potential mechanism of action
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