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

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.