Integrated network, docking, and experimental validation of the dual anti-inflammatory and uricosuric actions of Artemisia vulgaris compounds

• This study applied network pharmacology and docking to identify and prioritize A. vulgaris compounds. • followed by in vitro assays for experimental validation. • From an initial set of 62 phytochemicals, 52 compounds met drug-likeness criteria and were subsequently mapped to 277 overlapping gout-related targets. • Network analysis identified five top candidates, among which two emerged as most promising: AV52 (a flavonoid) and AV46 (artemisinin). • Docking predicted strong binding of AV52 to PTGS2 and xanthine oxidase (ΔG < –9.0 kcal.mol -1 ), suggesting dual anti-inflammatory and anti-hyperuricemic activity. AV46 showed high affinity for urate transporters (SLC22A12, ABCG2), supporting a complementary uricosuric role. • AV46 was selected for experimental validation due to availability. In LPS-stimulated RAW 264.7 macrophages, AV46 was non-cytotoxic and significantly suppressed IL-6 (68–94%) and TNF-α (55–75%), reduced nitrite (∼23–45%), while maintaining IL-10 levels. Consequently, the IL-10/IL-6 ratio increased 3–14 fold, indicating a pro-resolution immunomodulatory effect. • These findings propose a dual strategy: AV52 as a lead compound with combined anti-inflammatory and XO-inhibitory activity, and AV46 as a transporter-centric anti-inflammatory anchor. • This complementary paradigm supports A. vulgaris as a promising source of multi-target anti-gout agents, warranting further in vivo validation and formulation development to enhance bioavailability. In Traditional Chinese Medicine (TCM), mugwort ( Artemisia vulgaris ) is documented as the primary material for moxibustion, prepared as moxa floss ( ai rong , 艾绒), moxa cones ( ai zhu , 艾炷), and moxa sticks ( ai tiao , 艾条) to warm the channels and regulate qi–blood [ [6] , [7] , [8] ]. We therefore investigated A. vulgaris compounds for multi-target anti-gout relevance, anchored in these TCM indications. Network pharmacology and molecular docking prioritized A. vulgaris phytochemicals against gout-related targets, followed by in-vitro validation in LPS-challenged RAW 264.7 macrophages. Of 62 compounds, 52 met drug-likeness and intersected 277 gout genes. A flavonoid (AV52) showed strong predicted binding to PTGS2/XO, and artemisinin (AV46) to urate transporters (SLC22A12/ABCG2). Experimentally, AV46 reduced IL-6/TNF-α and nitrite while preserving IL-10. IL-10 showed a small, non-monotonic change at 6.25 µM (p < 0.05) that was not reproduced at adjacent doses, suggesting limited biological relevance, while overall IL-10 was preserved alongside reductions in IL-6 and TNF-α. Framed within TCM practice of moxibustion and warming/qi–blood-regulating indications, these data support a lead–anchor concept (AV52 anti-inflammatory/XO; AV46 uricosuric-anti-inflammatory) warranting further in-vivo and formulation studies for TCM-relevant applications. A. vulgaris phytochemicals demonstrate complementary potential against gout-related inflammation and urate handling within a TCM use-case anchored to mugwort preparations (moxa floss/cones/sticks). AV46 showed experimental activity consistent with predictions, while AV52 requires bench confirmation. These results motivate focused biochemical, transporter, pharmacokinetic, and in-vivo evaluations to support translation into Chinese preparation - compatible applications.