Micheliolide alleviates ankylosing spondylitis (AS) by suppressing the activation of the NLRP3 inflammasome and maintaining the balance of Th1/Th2 via regulating the NF-κB signaling pathway

Abstract

Background: Ankylosing spondylitis (AS) is a common form of inflammatory arthritis. Micheliolide (MCL), a sesquiterpene lactone, is reportedly involved in the alleviation of inflammatory response. This study aimed to investigate the mechanism of MCL in the treatment of AS.Methods: Mice were randomly divided into five groups: the sham group, the MCL (50 mg/kg) group, the AS model group, the AS + MCL (20 mg/kg) group, and the AS + MCL (50 mg/kg) group. After the addition of the inhibitor celastrol, mice were randomly divided into five groups: the sham group, the AS model group, the AS + MCL (50 mg/kg) group, the AS + Celastrol (1 mg/kg) group, and the AS + Celastrol (1 mg/kg) + MCL (50 mg/kg) group. Results:Compared with the AS model mice, the protein expression levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-18 were decreased after MCL treatment. The protein expression levels of capase-1 p10, IL-1β p17, NOD-like receptor family and pyrin domain containing 3 (NLRP3), caspase-1, and apoptosis-associated speck-like protein (ASC) were also reduced. The protein expression levels of Interferon (IFN)-γ were down-regulated, but levels of IL-4 were increased. Western blotting and immunohistochemistry revealed that the levels of p-IκB α were up-regulated, while the levels of phosphorylated-p65 were down-regulated. After the addition of celastrol, MCL treatment significantly reduced the levels of p-p65, NLRP3, caspase-1, and ASC. Meanwhile, the levels of IFN-γ were markedly down-regulated, but the levels of IL-4 were enhanced.Conclusions: Our study found that MCL suppressed the activation of NLRP3 inflammasome and maintained the balance of Th1/Th2 via regulating NF-κB signaling. Therefore, MCL could potentially be used to treat AS.

Autophagy Induced by Micheliolide Alleviates Acute Irradiation-Induced Intestinal Injury via Inhibition of the NLRP3 Inflammasome

“…The data gathered indicated that irradiation induces an inflammatory reaction accompanied by abundant production of pro-inflammatory cytokines, including IL-1β and IL-18. Interestingly, MCL alleviated radiation-induced intestinal damage and downregulated cytokine levels, consistent with previous reports ( Liu et al, 2019 ; Tian et al, 2020 ).…”

Identification of immune related cells and crucial genes in the peripheral blood of ankylosing spondylitis by integrated bioinformatics analysis

“…Animal experiments indicated that Micheliolide, a sesquiterpene lactone involved in alleviating the inflammatory response, maintained the balance of Th1/Th2 by regulating NF-κB signaling (Tian, Yao & Chen, 2020). Th17 cells were shown to be involved in AS (Xueyi et al, 2013).…”

“…Th1 and Th2 chemokine levels decreased under etanercept, a TNF-α blocker, to improve the activity and functional capacity of AS patients ( Ergin et al, 2011 ; Wang et al, 2016 ; Zhang et al, 2018 ). Animal experiments indicated that Micheliolide, a sesquiterpene lactone involved in alleviating the inflammatory response, maintained the balance of Th1/Th2 by regulating NF-κB signaling ( Tian, Yao & Chen, 2020 ). Th17 cells were shown to be involved in AS ( Xueyi et al, 2013 ).…”

Common mineral nutrients in ankylosing spondylitis: A 2‐sample Mendelian randomization study

“…17 These signaling pathways and inflammatory factors are also involved in the etiological mechanisms of AS. [18][19][20] Selenium is a necessary trace element for the human body.…”

“…Copper is a trace metal nutrient and excessive copper exposure can regulate the process of inflammation through various molecular and cellular signaling pathways, including the NF‐κB pathway, the Janus kinase‐signal transducer and activator of transcription pathway, and the nucleotide‐binding and oligomerization domain (NOD)‐like receptor protein 3 inflammasome 17 . These signaling pathways and inflammatory factors are also involved in the etiological mechanisms of AS 18–20 . Selenium is a necessary trace element for the human body.…”