Integrated Phytochemical, Immunological, and Network Pharmacology Investigation of Anti-Inflammatory Lignans From Zanthoxylum armatum Fruits.

Abstract

In the present study, bioactive lignans from Zanthoxylum armatum fruits have been investigated for their anti-inflammatory properties and evaluated using dendritic cell-based immunological assays and network pharmacology. The ethyl acetate fraction was subjected to bioassay-guided fractionation, chromatography, and HPLC to isolate pure compounds, characterised by NMR, LC-QTOF-MS, and single-crystal x-ray diffraction. Biological activities were evaluated using DPPH/ABTS radical scavenging assays, albumin denaturation and haemolysis inhibition assays, and flow cytometric analysis of IL-12p40/70 and CD80 expression in CpG-stimulated MuTuDC1940 dendritic cells. Sesamin exhibited the strongest antioxidant activity, while sesamin and fargesin showed notable anti-inflammatory effects. In CpG-stimulated MuTuDC1940 cells, sesamin reduced the proportion of IL-12-positive cells from 63.85% in the CpG-treated group to 52.67%, whereas fargesin (63.23%) showed little change and eudesmin (65.88%) showed a slight increase. Nevertheless, intracellular IL-12 MFI was significantly reduced by eudesmin, sesamin, and fargesin compared with CpG stimulation (p < 0.01), suggesting modulation of IL-12 expression intensity rather than a uniform reduction in the IL-12-positive cell population. Network pharmacology, PPI, GO, and KEGG analyses indicated involvement of PI3K-Akt, NF-κB, JAK-STAT, toll-like receptor, Rap1, and VEGF signalling pathways. These findings suggest these compounds may serve as potential natural therapeutics for inflammatory and immune-mediated diseases.