Zisheng Shenqi Decoction Ameliorates Monosodium Urate-Mediated Gouty Arthritis in Rats via Promotion of Autophagy through the AMPK/mTOR Signaling Pathway.

Gouty arthritis (GA) is an inflammatory disease owing to the accumulation of monosodium urate (MSU) in joints, leading to redness and burning pain. In this study, the effect of Zisheng Shenqi Decoction (ZSD) on a rat model of MSU-induced GA was investigated. ZSD obviously diminished the right paw thickness, the degree of the swelling of the paw, and the infiltration of the inflammatory cell, as well as cartilage erosion, and widened the joint space in MSU-treated rats. Besides, MSU remarkably elevated the release of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, and IL-18; however, ZSD treatment dose dependently lowered these levels and resulted in a significant decrease in articular elastase activity. Also, ZSD administration increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) but declined malondialdehyde (MDA) and nitrogen monoxide (NO) contents. Importantly, western blotting analysis revealed that NOD-like receptor protein 3 (NLRP3), cleaved caspase-1, IL-1ß, nuclear factor-E2-related factor 2 (Nrf2) in the cytoplasm, phosphorylated mammalian target of rapamyclin (p-mTOR), and p62 expressions were downregulated, whereas the levels of nuclear Nrf2, phosphorylated AMP-activated protein kinase (p-AMPK), Beclin-1, and LC3II/I were upregulated by ZSD. Immunofluorescence assay indicated that ZSD evidently promoted nuclear translocation of LC3. Taken together, ZSD inhibited inflammation and oxidative stress and facilitated autophagy through the activation of the AMPK pathway and suppression of the mTOR signaling pathway, demonstrating its potential for preventing and curing GA.

Zisheng Shenqi decoction ameliorates monosodium urate crystal-induced gouty arthritis in rats through anti-inflammatory and anti-oxidative effects.

Based on traditional Chinese medicinal theories on gouty arthritis, Zisheng Shenqi decoction (ZSD), a novel Chinese medicinal formula, was developed due to its multiple functions, including reinforcing renal function, promoting blood circulation and relieving pain. In the present study, the effect of ZSD on monosodium urate (MSU) crystal-induced gouty arthritis in rats was investigated and the underlying mechanisms were examined. The data from these investigations showed that the injection of MSU crystals into the ankle joint cavity caused significant elevations in ankle swelling and inflammatory cell infiltration into the synovium, whereas these abnormal changes were markedly suppressed by oral administration of ZSD (40 mg/kg) for 7 days. Mechanically, ZSD treatment prevented MSU crystal­induced inflammatory responses, as evidenced by downregulation in the expression levels of NACHT domain, leucine­rich repeat and pyrin domain containing protein (NALP) 1 and NALP6 inflammasomes, decreased serum levels of tumor necrosis factor­α and interleukin­1ß, and inhibited activation of nuclear factor­κB. In addition, ZSD administration markedly enhanced the anti-oxidant status in MSU crystal­induced rats by the increase in the activities of superoxide dismutase and glutathione peroxidase, and the levels of reduced glutathione. These results indicated that ZSD effectively prevented MSU crystal-induced gouty arthritis via modulating multiple anti­oxidative and anti­inflammatory pathways, suggesting a promising herbal formula for the prevention and treatment of gouty arthritis.