Ditan Qingnao decoction alleviates schizophrenia-like symptoms in a maternal immune activation-induced rat model via NF-κB/NLRP3 pathway inhibition

To investigate the efficacy and mechanism of Ditan Qingnao decoction (DTQND) in alleviating schizophrenia-like symptoms in a maternal immune activation (MIA)-induced rat model. DTQND components were analyzed using high-performance liquid chromatography–tandem mass spectrometry. An MIA-induced rat model was established by injecting Poly I:C into pregnant dams on gestational day 9. Male offspring were administered DTQND (14.1 g/kg), risperidone (RIS; 0.4 mg/kg), or distilled water, while the controls received only distilled water via gavage for 4 weeks. Behavioral assessments were conducted using the open-field, Y-maze, prepulse inhibition, and sucrose preference tests. Serum levels of interleukin (IL)-6, IL-18, IL-1β, and tumor necrosis factor-α (TNF-α) were measured via an enzyme-linked immunosorbent assay. Hippocampal protein levels of nuclear factor kappa B p65 (NF-κB p65), phospho–NF–κB p65 (p-p65), inhibitor of kappa B-alpha (IκB-α), phospho-IκB-α (p-IκB-α), and nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) were assessed via western blots. Immunohistochemistry detected hippocampal expression of ionized calcium-binding adapter molecule 1 (Iba1) and cluster of differentiation 68 (CD68). Multiple DTQND compounds were identified, including stachyose, β-syringin, and isofraxidin, among others. DTQND treatment considerably enhanced spontaneous activity, reduced anxiety, improved spatial working memory, and alleviated sensory gating defects in male offspring with MIA. The DTQND group showed significantly lower serum levels of IL-1β ( P = .002) and IL-18 ( P = .046) than the model group, with no discernible variations in IL-6 or TNF-α levels. In the hippocampus, DTQND significantly suppressed the expression of p-p65 ( P < .001), p-IκB-α ( P = .023), and NLRP3 ( P < .001) compared to the model group. Additionally, DTQND modulated microglial activation markers, decreasing CD68 expression ( P = .004) without affecting Iba1 levels. DTQND alleviated schizophrenia-like behavioral deficits and cognitive impairment by inhibiting the NF-κB/NLRP3 pathway, supporting its potential as an alternative therapy for schizophrenia.