Regulatory effect of berberine on NLRP3/TLRs in mice with gouty arthritis

Abstract:

Objective：To investigate the regulatory effect of berberine on NLRP3/TLRs signal pathway in mice with gouty arthritis. Methods：C57BL/6 mice were randomly divided into 6 groups：normal control group，model group，colchicine group（positive control，0.65 mg/kg），and berberine groups with high，middle and low doses（150，100，50 mg/kg），respectively. Administration for 7 days after modeled，and the swelling degree of the ankle joint was measured every day to observe therapeutic effects. Meanwhile，serum inter－leukin-2（IL-2），interleukin-6（IL-6），tumor necrosis factor-α（TNF-α） and interferon-α（IFN-α） expression levels were measured by ELISA. And the expressions of key target genes and proteins of NLRP3/TLRs in the mice's ankle synovial tissue were detected by RT-PCR and Western blot assays. Results：Compared with the model group（31.34%），the swelling degrees of the ankle joint of the berberine groups with high，medium and low doses（18.35%，21.35%，25.35%，respectively） and the colchicine group（15.35%） were significantly reduced，and the difference was statistically significant（F=11.240，P=0.005）. After the berberine treatment with different doses，inflammatory cell infiltration and edema in the ankle synovial tissue were significantly alleviated. The ELISA results showed that compared with the model group，the serum levels of IL-2，IL-6，TNF-α and IFN-α in the berberine groups were significantly decreased（IL-2：F=5.690，P=0.005；IL-6：F=10.370，P=0.009；TNF-α：F=15.240，P=0.002；IFN-α：F=4.520，P=0.020）. RT-PCR and Western blot results showed that the expression levels of NLRP3，TLR3，TLR7，MyD88 and NF-?资B p65 genes and proteins were obviously decreased in the mice's synovial tissue of the berberine groups with high，medium and low doses（P<0.05）. Conclusion：Berberine can alleviate gouty arthritis in mice，and its mechanism may be related to down-regulating inflammatory cytokine levels and inhibiting NLRP3/TLRs signal pathway.