Mechanistic study on the improvement of immune inflammation in ankylosing spondylitis through regulation of the PI3K/AKT signaling pathway by Huangqin Qingre Chubi capsules

ObjectiveThis study aims to investigate the potential mechanisms by which the Hangqin Qingrechubi capsule (HQC) improves immunoinflammation in Ankylosing Spondylitis (AS).MethodsThe study combines systemic network pharmacology to predict, identify, and validate the core targets of HQC and AS. We conducted molecular docking to validate the interaction between the key active ingredients of HQC and the selected core targets associated with the PI3K/AKT signaling pathway, and employed data mining to delve deeper into the correlation between HQC usage and the improvement of clinical immunoinflammatory indicators. Additionally, AS-PBMCs and FLS co-culture cell models will be employed to further explore the mechanism of action of HQC in improving AS immune inflammation.ResultsBased on network pharmacology core target prediction, TNF-alpha, IL-17A, IL-6, IL-10, and AKT1 were identified as core targets, and KEGG enrichment analysis suggested that PI3K/AKT, IL-17, and TNF might be key signaling pathways of HQC in improving immune inflammation in AS. The results of molecular docking demonstrated a favorable binding energy between the selected AKT1 core target and the key active components of HQC, including baicalin, baicalein, and quercetin. Clinical data mining revealed a significant correlation between HQC use and improvement in clinical immunoinflammatory indexes, such as ESR, CRP, IgA, IgM, IgG, C3, C4, patient perception scores (VAS, SAS, SDS), and (PF, SF) scores. In vitro cellular experiments further supported the significant ability of HQC to inhibit PI3K/AKT signaling pathway activation.ConclusionHQC, as an herbal compound preparation, exhibits anti-inflammatory effects through multiple components and targets, making it a potential treatment option for AS. Furthermore, an underlying mechanism of action of HQC is its ability to ameliorate immune inflammation in AS patients by inhibiting the PI3K/AKT signaling pathway.