Palmatine Protects Against MSU-Induced Gouty Arthritis via Regulating the NF-κB/NLRP3 and Nrf2 Pathways

超氧化物歧化酶 氧化应激 关节炎 化学 免疫印迹 药理学 肿瘤坏死因子α 丙二醛 谷胱甘肽 炎症 αBκ 促炎细胞因子 NF-κB 信号转导 免疫学 医学 生物化学 基因
作者
Juanjuan Cheng,Xingdong Ma,Gaoxiang Ai,Qiuxia Yu,Xiaoying Chen,Fang Yan,Yucui Li,Jianhui Xie,Ziren Su,Qingfeng Xie
出处
期刊:Drug Design Development and Therapy [Dove Medical Press]
卷期号:Volume 16: 2119-2132 被引量:43
标识
DOI:10.2147/dddt.s356307
摘要

Purpose: Gouty arthritis could be triggered by the deposition of monosodium uric acid (MSU) crystals. Palmatine (PAL), a protoberberine alkaloid, has been proven to possess compelling health-beneficial activities. In this study, we aimed to explore the effect of PAL on LPS plus MSU crystal-stimulated gouty arthritis in vitro and in vivo. Methods: PMA-differentiated THP-1 macrophages were primed with LPS and then stimulated with MSU crystal in the presence or absence of PAL. The expression of pro-inflammatory cytokines and oxidative stress-related biomarkers and signal pathway key targets were determined by ELISA kit, Western blot, immunohistochemistry and qRT-PCR, respectively. In addition, the anti-inflammatory and antioxidant activities of PAL on MSU-induced arthritis mice were also evaluated. Results: The results indicated that PAL (20, 40 and 80 μM) dose-dependently decreased the mRNA expression and levels of pro-inflammatory cytokines (interleukin-1beta (IL-1β), IL-6, IL-18 and tumor necrosis factor alpha (TNF-α)). The levels of superoxide dismutase (SOD) and glutathione (GSH) were remarkably enhanced, while the level of malondialdehyde (MDA) was reduced. Western blot analysis revealed that PAL appreciably inhibited NF-κB/NLRP3 signaling pathways through inhibiting the phosphorylation of p-65 and IκBα, blocking the expression of NLRP3, ASC, IL-1β and Caspase-1, as well as enhancing the antioxidant protein expression of Nrf2 and HO-1. In vivo, PAL attenuated MSU-induced inflammation in gouty arthritis, as evidenced by mitigating the joint swelling, and decreasing the productions of IL-1β, IL-6, IL-18, TNF-α and MDA, while enhancing the levels of SOD and GSH. Moreover, PAL further attenuated the infiltration of neutrophils into joint synovitis. Conclusion: PAL protected against MSU-induced inflammation and oxidative stress via regulating the NF-κB/NLRP3 and Nrf2 pathways. PAL may represent a potential candidate for the treatment of gouty arthritis. Keywords: palmatine, NF-κB/Nrf2 signal pathways, NLRP3 inflammasome, gouty arthritis
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