Protective Effects of Teucrium polium Extract Against LPS-Induced Oxidative Stress in BV-2 Microglia: Insights from Wild-Type and Acox1⁻/⁻ Models

Microglial activation and the associated oxidative or inflammatory responses play a crucial role in the development of neurodegenerative diseases. In this study, we evaluated the antioxidant, cytotoxic, and anti-inflammatory properties of Teucrium polium (TP) ethanolic extract in murine BV-2 microglial cells, including wild-type (Wt) and peroxisomal β-oxidation-deficient Acox1⁻/⁻ cell lines. The TP extract exhibited high antioxidant activity as assessed via the DPPH test, with an IC₅₀ value of 73.89 µg/mL, and contained substantial levels of total phenols (181.7 ± 2.1 mg GAE/g) and flavonoids (95.4 ± 3.1 mg QE/g). Cytotoxicity assessment revealed no detrimental effect on cell viability or proliferation at any tested concentration in either cell line. Exposure to lipopolysaccharide (LPS, 1 µg/mL) induced significant increases in catalase activity (35% in Wt, 95% in Acox1⁻/⁻) and gene expression (Cat mRNA upregulated 2-fold in Wt and 5-fold in Acox1⁻/⁻), nitric oxide (NO) production, and up-regulation of inflammatory markers (Tnf-α, iNos, Il-1β by ~10–15-fold) in both Wt and Acox1⁻/⁻ cells. Notably, co-treatment with TP extract effectively suppressed these LPS-induced changes, restoring catalase activity and expression to control levels and significantly reducing both NO (~10-fold) production and pro-inflammatory gene expression. The TP extract also modulated the expression of the peroxisomal transporter gene Abcd1, upregulating it in Wt cells while normalizing its expression in Acox1⁻/⁻ cells under LPS stimulation. These findings suggest that T. polium extract exhibits potent antioxidant and anti-inflammatory activities without cytotoxicity, and may modulate peroxisomal function and redox balance in microglial cells. The differential responses observed in Acox1⁻/⁻ cells point to the involvement of peroxisomal β-oxidation pathways in neuroinflammatory regulation. The results support the potential of T. polium as a neuroprotective agent in conditions associated with oxidative stress and peroxisomal dysfunction.