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

Abstract

Introduction

This study aimed to investigate the mechanism of Juanbi Lijieqing Decoction (JLD) in alleviating acute gouty arthritis (AGA) by modulating PPARγ expression to suppress the TLR4/NF-κB 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), the high-dose Juanbi Lijieqing Decoction group (Group C), the medium-dose group (Group D), the low-dose group (Group E), the etoricoxib group (Group F), and the pioglitazone group (Group G), with 12 rats per group. The acute gouty arthritis model was established by intraperitoneal injection of potassium oxonate, followed by monosodium urate (MSU) injection into the ankle joint, and then by pharmacological intervention in each group. The ankle swelling index, pain threshold changes, and serum uric acid levels were observed in each group of rats. 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 expressions of TLR4, NF-κB, and PPARγ were detected and using Western blot.

Results

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

Discussion

Our findings demonstrated that JLD alleviated acute gouty arthritis by upregulating PPARγ expression, which subsequently inhibited the TLR4/NF-κB signaling pathway. This mechanism effectively reduced inflammatory cytokine production (TNF-α, IL-1β, and IL-6), explaining the observed anti-swelling and analgesic effects.

Conclusion

JLD mitigates AGA symptoms by promoting PPARγ, which in turn inhibits TLR4/NF-κB signaling, thereby reducing inflammation, uric acid, and joint swelling. This highlights the therapeutic potential of JLD for gout management, though long-term effects and molecular targets warrant further study.

This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode.
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2025-07-03
2025-09-14
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/content/journals/cchts/10.2174/0113862073378606250616114958
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  • Article Type:
    Research Article
Keywords: TLR4 ; PPARγ ; chinese medicine ; NF-κB ; acute gouty arthritis ; Juanbi Lijieqing Decoction ; uric acid
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