Achillea erba-rotta subsp. moschata (Wulfen) I. Richardson Modulates Inflammatory and Antioxidant Pathways in Brain...

Background. Neuroinflammation, driven by chronic microglial activation and blood-brain barrier dysfunction, is increasingly recognised as a key pathogenic mechanism in neurodegenerative disorders. Achillea erba-rotta subsp. moschata, an alpine medicinal plant traditionally employed for inflammatory conditions, has demonstrated antioxidant and anti-inflammatory properties; however, its effects on brain-related cell types and the underlying neuropharmacological mechanisms remain largely unexplored. This study investigated the molecular pathways by which A. erba-rotta subsp. moschata modulates neuroinflammation in key cellular components of the neurovascular unit. Methods. We evaluated the pharmacological activity of A. erba-rotta subsp. moschata aqueous extract (20-200 µg/mL) in LPS-stimulated BV2 microglial cells and human brain microvascular endothelial cells (hBMECs). Molecular mechanisms were characterised using qRT-PCR and Western blot analysis, focusing on inflammatory, antioxidant (Nrf2/HO-1), and AhR signalling pathways. Results. A. erba-rotta subsp. moschata extract significantly attenuates inflammatory responses in both cell types. In BV2 microglia, the extract reduced pro-inflammatory mediators and promoted anti-inflammatory signalling, including dose-dependent upregulation of TGF-β. In parallel, in hBMECs, the extract preserved endothelial integrity and mitigated inflammation-induced alterations without affecting cell viability. At the molecular level, the extract modulated key transcriptional pathways involved in inflammation and redox homeostasis, including NF-κB and the Nrf2/HO-1 axis. Importantly, robust CYP1A1 induction indicated aryl hydrocarbon receptor (AhR) activation, revealing coordinated crosstalk between inflammatory and antioxidant pathways. Conclusions. A. erba-rotta subsp. moschata exerts balanced, tissue-dependent immunomodulatory activity through multi-target neuropharmacological mechanisms. The anti-inflammatory effects in microglia combined with barrier-preserving actions in brain endothelium, support its therapeutic potential as a neuropharmacological agent for neuroinflammatory disorders.