Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease (Ma et al., 2022; Zhao et al., 2023), primarily impacting the axial and sacroiliac joints (Xiong et al., 2022). It is characterized by inflammatory back pain and asymmetric peripheral joint synovitis (Navarro-Compán et al., 2021). Despite significant advancements, the AS pathogenesis remains complex and needs further exploration (Yu et al., 2021a). Insufficient and delayed diagnosis and treatment of patients lead to a gradual deformation, ankylosis, or disability of the spine, posing a severe threat to health and quality of life (Karoli et al., 2022). Additionally, decreased work capacity and reduced social participation of these patients impose economic and social burdens on society (Cui et al., 2022; Goel et al., 2023). Hence, there is an imperative need to undertake comprehensive research on the pathogenesis of AS and potential drug targets.

Inflammation is a central pathological process in the early onset and continuous progression of AS (Fu et al., 2022). This pathological process is closely related to immune responses mediated by substances such as antigens, cytokines, and receptor proteins. In the pathogenesis of AS, monocytes and related cytokines are intricately involved in promoting the inflammatory process (Liao and Tsai, 2023), thereby affecting the self-perception of patients (SPP) (Karatekin et al., 2023). Therefore, therapeutic strategies that aim to inhibit the immuno-inflammatory process in the body may benefit individuals with AS. Currently, the goals of AS management include attaining disease remission, controlling disease activity, and enhancing the quality of life for patients (Wang et al., 2020). Despite some advances in the pharmacological treatment of AS (Ramiro et al., 2023), these treatment drugs still carry risks of non-therapeutic effects (Danve and Deodhar, 2022; Webers et al., 2023). Consequently, there is a pressing necessity to further investigate new therapeutic agents.

Xinfeng Capsule (XFC; Anhui Medicine Production No. Z20050062; Patent No. ZL, 2013 1 0011369.8) is a proprietary formulation developed by the First Affiliated Hospital of Anhui University of Chinese Medicine. It contains a specific blend of Astragalus mongholicus Bunge (http://mpns.kew.org), Coix lacryma-jobi L. (http://mpns.kew.org), Tripterygium wilfordii Hook. f. (http://mpns.kew.org), and Scolopendra subspinipes mutilans L.Koch (https://db.ouryao.com), combined in a ratio of 20:20:10:1. Prior research has demonstrated that XFC adheres to rigorous quality standards as confirmed by high-performance liquid chromatography (HPLC) fingerprinting (Gao et al., 2021). In clinical trials targeting AS treatment, XFC has shown promising efficacy and safety (Fang et al., 2016a; Lei et al., 2022). Experimental studies have shown that XFC could regulate cytokines, inhibit excessive activation of NF-κB signal pathway, and improves thrombosis in patients with ankylosing spondylitis. In addition, it can negatively regulate the activation and proliferation of B cells, alleviate abnormal immune responses and oxidative stress damage, and effectively alleviate joint stiffness and pain (Fang et al., 2016b; Qi et al., 2015). Furthermore, our clinical data mining and network pharmacology studies suggested that XFC might improve immuno-inflammation in AS. The improvement mechanism may be attributed to the active components of XFC in regulating immuno-inflammation in AS (i.e., TNF-α, IL-6, IL-4, and IL-10) through the NF-κB pathway (Fang et al., 2022). However, further validation of the molecular-biological mechanisms is still lacking.

Existing evidence suggests that lncRNAs are involved in the immuno-inflammation of AS (Fang and Liu, 2023; Li et al., 2020). The team preliminarily identified long noncoding RNA (lncRNA) NONHSAT227927.1 using high-throughput sequencing as a significantly expressed lncRNA in AS-PBMCs. Subsequently, its capacity to promote immuno-inflammation in AS was clinically validated (Ding et al., 2023). Tumor necrosis factor receptor-associated factor 2 (TRAF2) is a trimeric protein member of the tumor necrosis factor receptor-associated factor (TRAF) family. This protein is crucial in signal transduction and involves various essential processes, including cell apoptosis, immune stimulation, and inflammation (Minicozzi et al., 2021). Previous research has demonstrated that TNF-α affects inflammatory reactions by binding to the extracellular domains of TNFR1 and TNFR2. However, TNFR1 is primarily associated with inflammation and tissue degeneration, and this interaction may lead to the recruitment of signaling molecules, including TRAF2 (Borghi et al., 2016). Activating the NF-κB signaling pathway, triggered by the recruitment of TRAF2, is crucial in promoting the release of inflammatory cytokines and chemokines (Zhao et al., 2020). Nevertheless, further research is needed to investigate whether lncRNA NONHSAT227927.1 activates the NF-κB pathway through TRAF2 to promote immuno-inflammation in AS.

The primary objective of this study was to elucidate the mechanism of the lncRNA NONHSAT227927.1/TRAF2/NF-κB axis in the immuno-inflammation of AS and XFC in AS treatment. The study also explored the impact of XFC on the SPP of patients with AS.