Juanbi Lijieqing Decoction Inhibits TLR4/NF-κB Signaling Pathway by Promoting PPARγ Expression to Relieve Acute Gouty Arthritis

Abstract

Objective: The objective of this study is to explore the mechanism by which Juanbi Lijieqing Decoction (JLD) alleviates acute gouty arthritis (AGA) by promoting PPARγ expression to inhibit the TLR4/NF-κB signaling pathway.

Methods: A total of 84 male SD rats were divided into 7 groups of 12 rats. One group was randomly selected as the normal control group (Group A), while the remaining 72 rats were used to establish an acute gouty arthritis model through intraperitoneal injection of potassium oxonate combined with MSU ankle joint injection. These rats were randomly assigned to the model group (Group B), high-dose Juanbi Lijieqing Decoction group (Group C), medium-dose group (Group D), low-dose group (Group E), etoricoxib group (Group F), and pioglitazone group (Group G), with 12 rats per group. The acute gouty arthritis model was established by intraperitoneal injection of potassium oxonate combined with monosodium urate (MSU) injection in the ankle joint, followed by pharmacological intervention in each group. The ankle swelling index, pain threshold changes, and serum uric acid levels in each group of rats were observed. The pathological state of synovial tissue in each group was evaluated by hematoxylin-eosin (HE) staining. The levels of TNF-α, IL-6, and IL-1β were detected by enzyme-linked immunosorbent assay (ELISA). The protein expression of TLR4, NF-κB, and PPARγ in vivo and in vitro were detected by Western blot.

Results: JLD effectively reduced local swelling, relieved pain, and lowered serum uric acid levels in rats with AGA. (2) Both in vivo and in vitro experiments demonstrated that the Chinese medicine groups showed a significant reduction in TNF-α, IL-1β, and IL-6 levels. Moreover, in in vivo experiments, the expression of PPARγ protein was significantly upregulated in the JLD and pioglitazone groups, while TLR4 and NF-κB p65 protein expressions were significantly downregulated, a pattern not observed in the etoricoxib group. In vitro experiments showed significant increases in PPARγ protein expression in the pioglitazone and medicated serum groups, with significant decreases in TLR4 protein expression. Meanwhile, the NF-κB inhibitor group only exhibited a downregulation of TLR4 protein expression.

Conclusion: This study demonstrates that JLD alleviates acute gouty arthritis symptoms by promoting the expression of PPARγ, which, in turn, inhibits the TLR4/NF-κB signaling pathway. This molecular mechanism results in reduced inflammation, lower serum uric acid levels, and decreased joint swelling. These findings provide valuable insight into the therapeutic effects of JLD in managing gout and suggest that it may serve as a promising adjunct to current treatment strategies. However, further studies are needed to fully elucidate its long-term effects and the precise molecular targets involved, paving the way for future clinical applications.

Keywords: Juanbi Lijieqing Decoction; NF-κB; PPARγ; TLR4; acute gouty arthritis..