Neuroinflammation is a self-defensive response of the central nervous system (CNS) to factors that interfere with its homeostasis. Under normal physiological conditions, neuroinflammation removes or inhibits harmful substances, helps the body to resist pathogens and maintains the stability of the internal environment (Chen et al., 2018). However, usually in response to nerve damage, infection and other factors, various immune cells are activated to release inflammatory mediators, resulting in an adaptive immune response (C and Lynch, 2020). Neuroinflammation is observed not only in neurological diseases that are inflammatory, such multiple sclerosis, but also in many non-inflammatory neurological diseases. Emerging evidences suggest that neuroinflammation is closely related to neurodegenerative diseases (Kempuraj et al., 2017), including amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) (Van Eldik et al., 2016), Huntington's chorea (HD) (Carson et al., 2006), and Parkinson's disease (PD). Neuroinflammatory pathway is considered as a potential therapeutic target for these diseases (Jung et al., 2019).

Microglia are the most important and predominate cells of the immune system in CNS, and make a significant contribution in the innate immune response, neurodevelopment and synaptic plasticity maintenance (Colonna and Butovsky, 2017; Vezzani and Viviani, 2015). Microglia are highly responsive to most forms of neuronal injury or toxins (e.g., LPS and β-amyloid) (Del Campo et al., 2021; Minis et al., 2019). Microglia respond to this activation state with morphological changes to maintain neurological homeostasis, such as somatic hypertrophy, increased branching, up-regulation of cell surface or intracellular molecules (Perry and Teeling, 2013). NF-κB is a crucial transcriptional regulator in cell. Microglia are quickly activated by pro-inflammatory stimulated and stressful situations, and this activation is made possible through the transcription factor NF-κB (Liu et al., 2017; Vallabhapurapu and Karin, 2009). Transcription of various genes, including those encoding inflammatory cytokines, chemokines, adhesion molecules, cytoprotective proteins, and immediate early genes (C and Lynch, 2020), which is triggered by activated NF-κB, that would lead to overproduction of factors such as superoxide, and TNF-α (Miraghazadeh and Cook, 2018), further exacerbating the disease. Thus, targeting NF-κB-mediated microglia activation may be regarded as an attractive effective strategy for the treatment of neuroinflammation.

Among soluble tyrosine protein kinases, Janus kinase (JAK) is an intracytoplasmic and non-receptor type. It was reported that Janus kinase - signal transducer and activator of transcription (JAK-STAT) signaling pathway is the most significant one in the downstream pathway of JAK, which was closely related to cell differentiation, proliferation, apoptosis and immune regulation (Jisha et al., 2017; Kumar et al., 2021; Rusek et al., 2023; Tomar et al., 2023; Yan et al., 2018). A possible therapeutic target in inflammatory diseases is the Janus kinase family (JAKs), which has a significant impact on cytokine signaling. Currently JAK inhibitors are under clinical development as an anti-inflammatory agent and immunosuppressant, which were used clinically to screen drugs for haematological disorders, oncology, rheumatoid arthritis and psoriasis (Daoud and Taha, 2020; Punwani et al., 2012; Salas et al., 2020). Ruxolitinib is a potent, highly selective, orally bioavailable JAK inhibitor. The US Food and Drug Administration (FDA) has authorized the JAK inhibitor ruxolitinib for the treatment of patients with myeloproliferative neoplasms and graft-versus-host disease (GVHD) (Quintás-Cardama et al., 2010). In addition, ruxolitinib has been found to reverse symptoms associated with haemophagocytic lymphohistiocytosis (HLH), and in particular, ruxolitinib treatment significantly reduced peripheral and CNS inflammation (Maschalidi et al., 2016). Given the effective therapeutic efficacy of JAK inhibitor ruxolitinib in inflammatory conditions, in our study, inhibitor ruxolitinib was analyzed and evaluated whether could inhibit neuroinflammation and to research relative latent mechanism. On this basis, JAK inhibitor ruxolitinib may be a promising therapeutic method for neuroinflammation.